Physiology - 2

Draw figs 9.10 & 9.12 and discuss the steps of skeletal muscle Excitation-Contraction Coupling.

(1.) Action potential propagated along muscle cell membrane and into T-tubules (2.) Ca2+ released from terminal cisternae (3.) Ca2+ binding to troponin removes blocking action of tropomyosin (4.) Cross-bridges bind, rotate, and generate force (5.) Ca2+ transported back into sarcoplasmic reticulum (6.) Ca2+ removal from troponin restores tropomyosin blocking action

Reproduce the hormonal profiles and ovarian events during the menstrual cycle as shown in figure 17.22. Read the figure legend carefully so that you may remember and locate all the details provided at each numbered location in the figure.

(1.) FSH and LH secretion increase (because plasma estrogen concentration is low and exerting little negative feedback) (2.) Multiple antral follicles begin to enlarge and secrete estrogen (3.) Plasma estrogen concentration begins to rise (4.) One follicle becomes dominant and secretes very large amounts of estrogen (5.) Plasma estrogen concentration increases markedly (6.) FSH secretion and plasma FSH concentration decrease causing atresia of non-dominant follicles (7.) Increasing plasma estrogen exerts a "positive" feedback on gonadotropin secretion (8.) An LH surge is triggered (9.) The egg completes its first meiotic division and cytoplasmic maturation while the follicle secretes less estrogen accompanied by some progesterone (10.) Ovulation occurs (11.) The corpus luteum forms and begins to secrete large amounts of both estrogen and progesterone (12.) Plasma estrogen and progesterone increase (13.) FSH and LH secretion are inhibited and their plasma concentrations decrease (14.) The corpus luteum begins to degenerate and decrease its hormone secretion (15.) Plasma estrogen and progesterone concentrations decrease (16.) FSH and LH secretions begin to increase and a new cycle begins

Using fig 9.9, list and discuss the events at the Neuromuscular Junction (NMJ).

(1.) Motor neuron action potential (2.) Ca2+ enters voltage-gated channels (3.) ACh release (4.) ACh binding opens ion channels (5.) Na+ entry (6.) Local current between depolarized end plate and adjacent muscle plasma membrane (7.) Muscle fiber action potential initiation (8.) Propagated action potential in muscle plasma membrane

Use both fig 17.25 and table 17.5 to describe hormonal events in the late follicular phase that lead to the LH surge and then the consequences of that LH surge.

(1.) The primary oocyte completes its first meiotic division and undergoes cytoplasmic changes that prepare the ovum for implantation should fertilization occur. These LH effects on the oocyte are mediated by messengers released from the granulosa cells in response to LH (2.) Antrum size (fluid volume) and blood flow to the follicle increase markedly (3.) The granulosa cells begin releasing progesterone and decreasing the release of estrogen, which accounts for the mid-cycle decrease in plasma estrogen concentration and the small rise in plasma progesterone concentration just before ovulation (4.) Enzymes and prostaglandins, synthesized by the granulosa cells, break down the follicular-ovarian membranes. These weakened membranes rupture, allowing the oocyte and its surrounding granulosa cells to be carried out onto the surface of the ovary. (5.) The remaining granulosa cells of the ruptured follicle (along with the theca cells of that follicle) are transformed into the corpus luteum, which begins to release progesterone and estrogen

Draw fig 9.15 and describe the steps of the Cross-bridge Cycle; be able to align the chemical reactions with the mechanical events.

(1.) [Ca2+] rises and cross bridge binds to actin [A-M-ADP-Pi] (2.) ADP and Pi detach and the cross bridge moves, power stroke [A-M] (3.) ATP binds to myosin, causing cross-bridge to detach from actin [A+M-ATP] (4.) Hydrolysis of ATP energizes cross-bridge [A+M-ADP-Pi] Repeats cycle

Using figs 17.10 and 17.12, describe the process of spermatogenesis and the production of mature spermatozoa. Be sure to enumerate the roles of Sertoli cells and Leydig cells.

- After several mitotic cycles (A to B), the spermatogonia differentiate (B) to give rise to primary spermatocytes (C) - Each spermatocyte crosses a tight junction, enlarges (D), and divides into two secondary spermatocytes (E) - Secondary spermatocytes divide into spermatids (F), which differentiate into spermatozoa (G) - Spermatozoa enter the lumen of the seminiferous tubule

Use fig 9.8 to draw and label the parts of a Neuromuscular Junction (NMJ).

- Alpha motor neurons synapse on skeletal muscle fibers near the fiber's center at specialized synapses known as neuromuscular junctions (NMJs) - The motor end plate is the highly folded region of the muscle's sarcolemma that lies directly beneath the alpha motor axon terminal at the NMJ

Using fig 17.19, depict the summary of oogenesis. Include all steps, labels, and details.

- Before birth, oogonium divides mitotically to give rise to 2-4 million oogonia (this process ceases 7 months after conception) - Just before birth, oogonia begin first meiotic division, but do not complete it (division is completed prior to ovulation). Oogonia are now known as primary oocytes

Describe the regulation of smooth muscle via the Autonomic Nervous System (ref Figure 9.37).

- Excitatory or inhibitory inputs - Neurotransmitters from autonomic axons are released from varicosities (swellings) - Sympathetic or parasympathetic (NorEpi or ACh) - Response of smooth muscle depends on type of receptor the cell has NOT the type of neurotransmitter

Draw fig 17.24 and summarize the hormonal control of ovarian function during the early and middle parts of the follicular phase.

- FSH onto Granulosa cells - LH onto Theca cells - Androgens are secreted by theca cells but converted to estrogen by granulosa cells (aromatase) - Inhibin produced by granulosa cells Negative feedback - Hypothalamus via estrogen - Primary target is the anterior pituitary - Inhibin released by granulosa cells preferentially inhibit FSH secretion - Both estrogen and progesterone are required to completely inhibit LH (estrogen inhibition is weak by itself)

Draw fig 17.14 and discuss the hormonal regulation of testes and spermatogenesis.

- GnRH stimulates secretion of peptide gonadotropins FSH and LH - LH has a tropic effect on Leydig cells to stimulate testosterone secretion - Testosterone plus FSH stimulate Sertoli cells to activate spermatogenesis and produce Inhibin - Peptide Inhibin specifically inhibits FSH secretion from the anterior pituitary

Draw both figs 9.17 and 9.18 and explain how the different loads give rise to the changes in the isotonic shortening distance, shortening velocity, latent period duration, and shortening duration.

- The distance shortened, velocity of shortening, and duration of shortening all decrease with increasing load - The time from stimulation to the beginning of shortening increases with increasing load

List and discuss the actions of thyroid hormone.

1.) Affects virtually every cell -> increased gene transcription and protein synthesis (esp. metabolism related gene products) 2.) Controls basal metabolic rate (BMR) and thus body temperature (rate at which cells burn fuel to maintain basic life functions, mainly by increased Na+/K+ ATPase) 3.) Permissive of B-adrenergic receptor (catecholamine) expression 4.) Essential for fetal CNS development and function; Equally important for proper adult nervous system function 5.) Permissive for overall growth and development

Similarities between smooth and skeletal muscle

1.) Both contain thick, myosin filaments and thin, actin filaments 2.) An increase in cytosolic Ca2+ is the key step in the E-C coupling process 3.) ATP is directly used to power cross-bridge cycling 4.) Sliding filament mechanism of contraction applies to both But, many differences...

Use figs 11.6 and 11.8 to discuss the synthesis and secretion of steroid hormones in the adrenal cortex and gonads respectively.

1.) Hormone producing cells are stimulated by the binding of an anterior pituitary gland hormone to its plasma membrane receptor 2.) Gs proteins activate second messenger systems which phosphorylate intracellular proteins 3.) Cholesterol undergoes several enzymatic conversions (dependent on the type of enzymes expressed by the cell) 4.) The final steroid hormone diffuses into the blood stream where they are bound to carrier proteins

Using fig 11.25, describe the three-gland, three-hormone cascade that depicts the regulated secretion of cortisol and how negative feedback keeps everything in balance.

1.) Hypothalamus releases corticotropin-releasing hormone (CRH) into the portal vessel which travels to the 2.) Anterior pituitary, specifically the corticotroph cells release adrenal corticotropin hormone (ACTH) into circulation which travels to 3.) The adrenal cortex, specifically zona fasciculata cells release cortisol (a steroid) into circulation which travels to 4.) Target cells for cortisol -> cellular response

Using fig 11.22, draw in detail the steps of thyroid hormone synthesis, storage, and regulated secretion.

1.) Iodide is cotransported with Na+ 2.) Iodide diffuses to the inner membrane of the follicle cell 3.) Iodide is transported to colloid, oxidized and attached to rings of tyrosines in thyroglobulin (TG) 4.) The iodinated ring of one monoiodotyrosine (MIT) or diiodotyrosine (DIT) is added to a DIT at another spot 5.) Endocytosis of thyroglobulin containing T3 and T4 molecules 6.) Lysosomal enzymes release T3 and T4 from TG 7.) T3 and T4 are secreted out of the cell and into capillaries

Reproduce both parts of fig 9.16b and explain the isotonic twitch events and data. Thoroughly describe how the load affects the four characteristics of an isotonic twitch.

1.) Isotonic latent period is longer than isometric latent period 2.) The velocity of shortening gets slower with increasing load 3.) Duration of shortening gets shorter with increasing load 4.) Distance shortened (load moved) gets smaller with increasing load

Make a table that enumerates the roles for ATP in smooth muscle cells.

1.) Na+/K+ ATPase pump maintains Na+ and K+ gradients, allowing for action potentials 2.) Ca2+ ATPase pump in the sarcoplasmic reticulum actively transports Ca2+ ions into the reticulum ending a muscle contraction 3.) Myosin ATPase uses ATP to energize the cross-bridges providing energy for force generation 4.) Binding of ATP to myosin dissociates cross-bridges bound to actin allowing bridges to repeat their cycle of activity ALSO 5.) Phosphorylation of myosin light chain by MLCKinase; this is a separate ATP molecule

Use fig 9.22 to describe the basics of skeletal muscle energy metabolism; specifically identify the three sources of intracellular ATP and label each as dominant in Aerobic or Anaerobic conditions.

1.) Phosphorylation of ADP by creatine phosphate - Fast source of ATP which acts before the cell has time to form ATP via other methods 2.) Oxidative phosphorylation of ADP in the mitochondria - Provides most of the ATP used for muscle contraction at moderate levels of activity - Aerobic - Occurs in mitochondria 3.) Glycolysis - Phosphorylation of ADP by the glycolytic pathway in the cytosol - Contributes an increasingly significant fraction of total ATP as exercise intensity exceeds 70% of the maximal rate of ATP breakdown - Anaerobic - Occurs in cytosol

Reproduce table 17.2 to summarize the functions of Sertoli cells.

1.) Provide Sertoli cell barrier to chemicals in the plasma 2.) Nourish developing sperm 3.) Secrete luminal fluid, including androgen-binding protein 4.) Respond to stimulation byterm-50 testosterone and FSH to secrete paracrine agents that stimulate sperm proliferation and differentiation 5.) Secrete the protein hormone inhibin, which inhibits FSH secretion from the pituitary gland 6.) Secrete paracrine agents that influence the function of Leydig cells 7.) Phagocytize defective sperm 8.) Secrete Anti-Müllerian hormone (AMH), which causes the primordial female duct system to regress during embryonic development

Use table 17.3 to list and summarize the effects of testosterone in the human male.

1.) Required for initiation and maintenance of spermatogenesis (acts via Sertoli cells) 2.) Decreases GnRH secretion via an action on the hypothalamus 3.) Inhibits LH secretion via a direct action on the anterior pituitary gland 4.) Induces differentiation of male accessory reproductive organs and maintains their function 5.) Induces male secondary sex characteristics; opposes action of estrogen on breast growth 6.) Stimulates protein anabolism, bone growth, and cessation of bone growth 7.) Required for sex drive and may enhance aggressive behavior 8.) Stimulates erythropoietin secretion by kidneys

List and discuss three essential contractile characteristics of smooth muscle (use the lecture slides).

1.) Slow cross-bridge cycling - 3 second twitch vs 100 msec for skeletal muscle 2.) Wide variability in patterns of contradtion - Phasic vs tonic contractions 3.) Broad length-tension curve - Smooth muscle can generate significant force even after being stretched

Use fig 11.4 to discuss the sequential synthesis and secretion of typical peptide hormones

1.) Synthesized by ribosomes as larger molecules called preprohormones 2.) Proteolytic enzymes in the rough ER cleave preprohormones into prohormones 3.) Prohormones packaged into secretory vesicles by the Golgi apparatus (Prohormone cleaved during post-translational processing to yield active hormone) 4.) Hormones stored in secretory vesicles 5.) Hormones secreted from vesicles via exocytosis (along with other peptides)

Using fig 17.8, locate and describe the essential functional anatomy of the male reproductive tract.

1.) Testes (steroid production, gametogenesis) 2.) Epididymus (sperm storage) 3.) Vas deferens (duct work) 4.) Seminal vesicles (fructose, prostaglandins) 5.) Prostate (alkaline mucus, clotting factors) 6.) Bulbourethral glands 7.) Penis (more ductwork)

Draw a detailed diagram showing the steps of cardiac E-C coupling (reference fig 9.40).

1.) The membrane is depolarized by Na+ entry as an action potential begins 2.) Depolarization opens L-type Ca2+ channels in the T-tubules 3.) A small amount of "trigger" Ca2+ enters the cytosol contributing to cell depolarization. That trigger Ca2+ binds to, and opens, ryanodine receptor Ca2+ channels in the sarcoplasmic reticulum membrane 4.) Ca2+ flows into the cytosol, increasing the Ca2+ concentration 5.) Binding of Ca2+ to troponin exposes cross-bridge binding sites on thin filaments 6.) Cross-bridge cycling causes force generation and sliding of thick and thin filaments 7.) Ca2+ ATPase pumps return Ca2+ to the sarcoplasmic reticulum 8.) Ca2+ ATPase pumps and Na+/Ca2+ exchangers remove Ca2+ from the cell 9.) The membrane is repolarized when K+ exits to end the action potential

List and describe five important characteristics of hormone receptors.

1.) They determine which tissues respond to an endocrine broadcast 2.) High sensitivity (10^-12M) 3.) Huge signal amplification (b/c of signal transduction mechanisms) 4.) Hormone levels influence expression of their own receptors - Continued High [H] -> Down-regulation, decreased # of receptors - Continued Low [H] -> Up-regulation, increased # of receptors 5.) Hormones can have a permissive effect on expression of OTHER hormones' receptors

Use figs 9.3, 9.4, and 9.11 to identify and define the molecular basis of skeletal muscle contraction.

Activation of myosin cross-bridges exert force on the thin filaments

Make a list of the functions for adrenal catecholamines in stress.

Adrenal Catecholamines - Dilates respiratory airways/increases ventilation - Dilates blood vessels to heart and skeletal muscle - Dilates pupils and increases cardiac function - Mobilizes glucose (from liver), triglycerides (from adipose) - Increases CNS alertness - Reduces digestive activity - Inhibits bladder emptying

Compare all 3 types of muscle cells, enumerating how they are similar and how they are different (reference Table 9.6).

All three types - Sliding filaments and cross bridges - ATP powers the force generation - Elevated cytosolic Ca2+ initiates contraction Cardiac and skeletal similarities - Has sarcomeres - Is striated - Has troponin - Has t-tubules - Relies on SR Ca2+ Cardiac and smooth similarities - Has pacemaker cells - Has gap junctions (syncytium) - Uses Ca2+ entry from ECF - Autonomic/Hormone regulated

Describe the time relationship between a skeletal muscle fiber action potential and the resulting contraction and relaxation of the muscle

An action potential in a skeletal muscle fiber lasts 1 to 2 msec and is completed before any signs of mechanical activity begin The electrical activity in the plasma membrane does not directly act upon the contractile proteins, instead it increases the cytosolic Ca2+ concentration Continues to activate the contractile apparatus long after the electrical activity has ceased

Describe the Anterior pituitary gland. List its secretions; include the hormone's name, the abbreviation, its chemical class, and its major target/effect within the body.

Anterior Pituitary - Endocrine cells which release hormones in response to hypophysiotropic hormones from the hypothalamus Releases 6 peptide hormones: FSH (follicle-stimulating hormone) LH (luteinizing hormone) - Targets the gonads causing germ cell development and hormone secretion GH (growth hormone) - Liver and other cells - secrete IGF-1 - Various organs/tissues - Protein synthesis, carbohydrate and lipid metabolism TSH (thyroid stimulating hormone) - Thyroid - Secretes thyroxine and triiodothyronine Prolactin - Breasts - Breast development and milk production in women ACTH (adrenocorticotropic hormone) - Adrenal cortex - secretes cortisol

Using fig 17.21, locate and describe the major ovarian events during the menstrual cycle. Distinguish between the follicular phase and the luteal phase of the menstrual cycle as well.

Assuming no fertilization Follicular phase - development of mature follicle and secondary oocyte Luteal phase - begins upon ovulation and lasts until the death of the corpus luteum - preparation for pregnancy if fertilization occurs

Define these terms with words and illustrate with diagrams (reference Figures 1.9 and 11.1): autocrine signaling, paracrine signaling, neurotransmitter signaling, endocrine signaling, exocrine signaling, neuroendocrine signaling.

Autocrine signaling - Autocrine substance acts on same cell that secreted the substance Paracrine signaling - Paracrine substance acts on target cells which are in close proximity to the site of substance release Neurotransmitter signaling - Neurotransmitter acts on neuron or effector cell in close proximity to site of neurotransmitter release Endocrine signaling - A gland secretes a hormone into the blood which affects target cells in one or more distant places in the body Exocrine signaling - Chemicals are secreted out of the body Neuroendocrine signaling - The release of a chemical from an axon terminal into the blood which affects target cells in one or more distant places in the body

Make a list of the functions for cortisol in the resting unstressed condition; provide rationales for all these secretions when they occur.

Basal levels 1.) Metabolic effects: Liver glucose production between meals - provides substrates and maintain enzymes involved in metabolic homeostasis) 2.) Permissive of adrenergic receptors in the cardiovascular system - Maintain adequate MAP 3.) Anti-inflammatory/anti-immune - Prevents hyper-response (drugs cortisone, prednisone, dexamethasone) 4.) Fetal/neonatal development of brain, intestines, lungs, glands - Production of surfactant in last months of gestation

Using fig 17.20, draw and discuss the sequential development of a human oocyte and ovarian follicle. Enumerate the changes at each phase and the purpose of each change.

Before birth, the primary oocytes exist as primordial follicles - In childhood and during the menstrual cycle, a portion of the resting primary follicles progress to pre-antral/early antral follicles - In the growing follicles, granulosa cells (with the help of theca cells) secrete estrogen - At the beginning of the menstrual cycle, 10-25 of the early antral follicles begin to enlarge, but usually only one survives (dominant follicle) - Throughout a woman's reproductive life, only about 400 follicles reach the mature follicle stage and release the oocyte (ovulation) - the rest undergo atresia (programed cell death)

Describe and draw (how and where) BoTox, Curare, and organophosphates disrupt the NMJ (reference pages 264-265)

BoTox - Blocks the release of acetylcholine from axon terminals by breaking down the SNARE complexes Curare (also rocuronium & vecuronium) - Nicotinic ACh receptor antagonist (binds and blocks preventing opening of ion channels, EPP and muscle contraction) - Can cause death by asphyxiation Organophosphates - Acetylcholinesterase inhibitor, prevents enzymatic destruction of ACh - Prevents generation of action potentials initially followed by desensitization of receptors to ACh - Skeletal muscle paralysis and death by asphyxiation

Discuss the location and function of cardiac muscle (reference figure 12.9).

Cardiac muscle changes the volume of the atria and ventricles in order to pump blood The inter-ventricular septum is composed of myocardium

Draw fig 17.26 and explain the hormonal control of ovarian function during the luteal phase.

Corpus luteum secretes large quantities of progesterone and estrogen as well as inhibin which causes a decrease in the secretion of the gonadotropins by the pituitary gland -> Low plasmas concentration of gonadotropins during the luteal phase If no fertilization the corpus luteum degrades within two weeks leading to an increase in FSH and LH (restarts the cycle)

Using fig 11.7, draw and describe the adrenal gland, correctly locating the cortex and medulla. List the secretions of all the layers/zones and include their chemical classes.

Cortex Zona glomerulosa - Aldosterone (steroid) Zona fasciculata - Cortisol and small amts of androgens (steroid) Zona reticularis - Androgens and small amts of cortisol (steroid) Medulla - Epinephrine and norepinephrine (catecholamines) Preferential presence of enzymes defines layers

Distinguish between diagnoses of Cushing's Syndrome versus Cushing's Disease. Give details that would be common to both versus those that would be different.

Cushing's Syndrome An excess of cortisol in the blood due to a primary defect (cortisol secreting tumor of the adrenal gland) Cushing's Disease An excess of cortisol in the blood due to a secondary defect (ex. ACTH secreting tumor of the anterior pituitary gland) Symptoms Osteoporosis, hyperglycemia, high blood pressure, immunosuppression, obesity of trunk and face with wasting of arms and legs

Using fig 11.27, draw a long bone and label its relevant parts to bone growth.

Epiphyses - The ends of the bone Shaft - The area in between the epiphyses Epiphyseal growth plate - A plate of actively proliferating cartilage Chondrocytes - Lay down new cartilage in the interior of the growth plate Osteoblasts - Bone forming cells convert the cartilaginous tissue to bone

Reproduce table 17.4 to understand the major effects of the three hormones listed.

Estrogen in low plasma concentrations, causes the anterior pituitary gland to secrete less FSH and LH in response to GnRH and also inhibits the hypothalamic neurons that secrete GnRH Result: Negative feedback inhibition of FSH and LH secretion during the early and middle follicular phase Inhibin acts on the pituitary gland to inhibit the secretion of FSH Result: Negative feedback inhibition of FSH secretion Estrogen when increasing dramatically, causes anterior pituitary gland cells to secrete more LH and FSH in response to GnRH. Estrogen also stimulates the hypothalamic neurons that secrete GnRH. Result: Positive feedback stimulation of the LH surge, which triggers ovulation Progesterone, in high plasma concentrations (in the presence of estrogen) inhibits the hypothalamic neurons that secrete GnRH. Result: Negative feedback inhibition of FSH and LH secretion and prevention of LH surges during the luteal phase and pregnancy.

Discuss smooth muscle locations and functions in the human body (use your lecture slides)

Functions - Regulates blood flow by changing vessel diameter - Regulates airway diameter - Helps in expulsion of urine from body - Helps in delivery of a baby during childbirth - Helps mix and propel food through the digestive tract

Reproduce table 17.6 to explain the granulosa cell functions during the menstrual cycle.

Granulosa cell functions - Nourish oocyte - Secrete chemical messengers that influence the oocyte and the theca cells - Secrete the antral fluid - The site of action for estrogen and FSH in the control of follicle development during early and middle follicular phases - Express aromatase, which converts androgen (from theca cells) to estrogen - Secrete inhibin, which inhibits FSH secretion via an action on the pituitary gland - The site of action for LH induction of changes in the oocyte and follicle culminating in ovulation and formation of the corpus luteum

Using tables 11.4 and 11.5, discuss the major effects of growth hormone and other hormonal influences on growth in the body. Include the metabolic effects of growth hormone as well.

Growth Hormone I. Promotes growth: Induces precursor cells in bone and other tissues to differentiate and secrete insulin-like growth factor 1 (IGF-1), which stimulates cell division. Also stimulates liver to secrete IGF-1 II. Stimulates protein synthesis, predominantly in muscle III. Anti- insulin effects (esp at high concentrations) A.) Renders adipocytes more responsive to stimuli that induce breakdown of triglycerides, releasing fatty acids into the blood. B.) Stimulates gluconeogenesis C.) Reduces the ability of insulin to stimulate glucose uptake by adipose and muscle cells, resulting in higher blood glucose concentrations

Use section 17.21 and fig 17.34 to discuss the role of hCG in pregnancy.

Human Chorionic Gonadotropin (hCG) - Secreted by the developing embryo - The basis for pregnancy tests (hCG in maternal urine) - Rescues the corpus luteum (LH-like; keeps the progesterone/estrogen factory open) - Mediates implantation - Turns on testosterone production in male fetus testes Decreases when after the placental luteal shift - placenta is the new producer of estrogen

Using Table 11.1, describe the receptor location(s) of hydrophilic hormones. What happens in general when a hydrophilic hormone binds to its receptor? (reference figure 5.6 as an example)

Hydrophilic hormone receptors tend to be located on the plasma membrane of the cell Hydrophilic hormone receptors trigger 1.) Second messengers (e.g., cAMP, Ca2+, IP3) 2.) Enzyme activation by receptor (e.g., JAK) 3.) Intrinsic enzymatic activity of receptor (e.g., tyrosine autophosphorylation)

Describe the receptor location(s) of hydrophobic hormones. What happens in general when a hydrophobic hormone binds to its receptor? (reference figure 5.4)

Hydrophobic hormone receptors tend to be located intracellularly These receptors tend to have a direct influence on gene transcription upon the binding of the hormone

Using the lecture slides, describe how long bones actually get longer during the growth process.

Hyperplasia - Chondrocytes undergo cell division at the top of the growth plate Hypertrophy - Older chondrocytes enlarge and secrete cartilage Osteoblasts on the shaft side of the epiphyseal growth plate convert cartilage to bone

Define and distinguish between the general types of endocrine disorders: Hypo and Hyper-secretion Hypo and Hyper-responsiveness

Hypersecretion - Too much hormone; pathology where negative feedback is ignored Hyposecretion - Too little hormone; often glandular destruction or loss of key regulators Hyper-responsiveness - Receptor up-regulation or altered functions within the second messenger cascades Hypo-responsiveness - Receptor down-regulation or altered functions within the second messenger cascades

Using section 11.12, distinguish between hypo and hyper-thyroid hormone conditions; use fig 11.23 to describe how and why a goiter could be present in either thyroid state.

Hypo-thyroidism - Any condition characterized by plasma concentrations of thyroid hormones that are chronically below normal Caused by: 1.) Damage to or loss of functional thyroid tissue 2.) Inadequate Iodine consumption 3.) Autoimmune thyroiditis - autoimmune disruption of the normal function of the thyroid gland (ex. Hashimoto's disease) Symptoms: Low BMR, cold intolerance, fatigue, inappropriate weight gain, weak pulse, decreased alertness and cognitive function Goiter Loss of negative feedback to hypothalamus and anterior pituitary causes increased secretion of TRH and TSH - Increased stimulation of TSH receptor has trophic effects on the thyroid gland Hyper-thyroidism - Any condition characterized by plasma concentrations of thyroid hormones that are chronically above normal Caused by: 1.) Auto-immune stimulation of TSH receptors (Graves disease) - TSI (thyroid stimulating immunoglobulins) antibodies mimic TSH hormone, stimulating receptor (LOTS of T3/T4 released) - NO negative feedback on these antibodies Symptoms: High BMR, heat intolerance, nervous/irritability, insomnia, inappropriate weight loss, constant fight or flight state, and exophthalmos (eyes pushed forwards). Goiter: TSI mimics TSH leading to chronic stimulation of TSH receptor - Increased stimulation of TSH receptor has trophic effects on the thyroid gland

Use figs 11.18 and 11.19 to list and describe the hypophysiotropic hormones. Include the name, the abbreviation, its chemical class, and its major effect on the anterior pituitary.

Hypophysiotropic hormones - Hormones released by the hypothalamus which regulate anterior pituitary function - All peptides except DA (catecholamine) GnRH - Gonadotropin-releasing hormone Stimulates secretion of LH and FSH GHRH - Growth hormone-releasing hormone Stimulates the secretion of GH SST - Somatostatin Inhibits the secretion of GH TRH - Thyrotropin-releasing hormone Stimulates the secretion of TSH DA - Dopamine Inhibits the secretion of prolactin CRH - Corticotropin-releasing hormone Stimulates the secretion of ACTH

Draw and discuss the mechanism of smooth muscle Excitation-Contraction Coupling; highlight the roles for kinases and phosphatases as shown in fig 9.34.

Increased cytosolic Ca2+ concentration 1.) Ca2+ binds to calmodulin, a Ca2+ binding protein that is present in the cytosol of all cells (structurally related to troponin) 2.) The Ca2+-calmodulin complex binds to another cytosolic protein, myosin light-chain kinase, activating this enzyme 3.) Active myosin light-chain kinase then uses ATP to phosphorylate myosin light chains in the globular head of myosin 4.) Phosphorylation of myosin drives the cross-bridge away from the thick filament backbone, allowing it to bind to actin 5.) Cross bridges go through repeated cycles of force generation as long as myosin light chains are phosphorylated

Use table 9.5 and your lecture slides to draw and enumerate the various mechanisms that elevate cytosolic calcium in smooth muscle.

Inputs influencing smooth muscle contractile activity 1.) Spontaneous electrical activity in the plasma membrane of the muscle cell (pacemakers and slow waves) 2.) Neurotransmitters released by autonomic neurons 3.) Hormones (eg. oxytocin) 4.) Locally induced changes in the chemical composition (paracrine factors, acidity, oxygen, osmolarity, and ion concentrations) of the extracellular fluid surrounding the cell 5.) Stretch mechanoreceptors (eg. in the blood vessels and GI tract)

Describe the histology of cardiac muscle cells, defining and explaining: intercalated discs, desmosomes, gap junctions (reference fig 9.39).

Intercalated discs Intersection of two neighboring cells Desmosomes "spot weld" - provides mechanical adhesion between two muscle cells Gap junctions - Electrical synapse between adjacent cells

Using the lecture slides differentiate between isometric and isotonic contractions; then further differentiate between concentric and eccentric contractions.

Isometric contraction - Muscle develops tension but does not change length - Tension development - Cross bridges cycle - Same length The rotation (power-stroke) of myosin head in cross bridge cycle is absorbed within the fibers elastic elements Isotonic contraction - Muscle changes in length while the load on a muscle remains constant - Tension development - Cross bridges cycle - Change in length Concentric Muscle shortens (Tension is greater than the load) Eccentric Muscle lengthens (Load is greater than tension)

Describe the purpose and function of the Leydig cells

Leydig cells ("interstitial") Interstitial cells which lie in small, connective-tissue spaces between tubules - Synthesize and release testosterone - After several mitotic cycles (A to B), the spermatogonia (B) give rise to primary spermatocytes (C) - Each spermatocyte crosses a tight junction, enlarges (D), and divides into two secondary spermatocytes (E) - Secondary spermatocytes divide into spermatids (F), which differentiate into spermatozoa (G) - Spermatozoa enter the lumen of the seminiferous tubule

List and describe the properties and characteristics of Peptide/Protein Hormones (use Table 11.1)

Major Form in Plasma Free (unbound) Location of Receptors Plasma membrane Most Common Signaling Mechanisms 1.) Second messengers (e.g., cAMP, Ca2+, IP3) 2.) Enzyme activation by receptor (e.g., JAK) 3.) Intrinsic enzymatic activity of receptor (e.g., tyrosine autophosphorylation) Rate of Excretion/Metabolism Fast (minutes) (Same as catecholamines)

List and describe the properties and characteristics of Catecholamine Hormones (use Table 11.1).

Major Form in Plasma Free (unbound) Location of Receptors Plasma membrane Most Common Signaling Mechanisms 1.) Second messengers (e.g., cAMP, Ca2+, IP3) 2.) Enzyme activation by receptor (e.g., JAK) 3.) Intrinsic enzymatic activity of receptor (e.g., tyrosine autophosphorylation) Rate of Excretion/Metabolism Fast (minutes) (Same as peptides)

List and describe the properties and characteristics of Thyroid Hormone (use Table 11.1).

Major Form in Plasma Protein-bound Location of Receptors Intracellular Most Common Signaling Mechanisms Intracellular receptors directly alter gene transcription Rate of Excretion/Metabolism Slow (hours to days) (Same as steroid hormone)

List and describe the properties and characteristics of Steroid Hormones (use Table 11.1).

Major Form in Plasma Protein-bound Location of Receptors Intracellular Most Common Signaling Mechanisms Intracellular receptors directly alter gene transcription Rate of Excretion/Metabolism Slow (hours to days) (Same as thyroid hormone)

Draw fig 17.27 and describe the relationships between the ovarian and uterine changes during the menstrual cycle. Be sure to properly align the 3 uterine phases with the 2 ovarian phases.

Menstrual phase (during follicular), Day 28 - 5, the endometrium degenerates resulting in the menstrual flow Proliferative phase (during follicular), Day 5 - 14, the menstrual flow ceases and the endometrium begins to thicken as it regenerates under the influence of estrogen Secretory phase (during luteal), Day 14 - 28, the endometrium begins to secrete glycogen in the glandular epithelium, followed by glycoproteins and mucopolysaccharides

Use figs 9.23 and 9.25 to define and describe skeletal muscle fatigue; discuss what is known regarding its development.

Muscle fatigue - Decline in muscle tension as a result of previous contractile activity - Different muscle types fatigue at different rates Decrease in ATP and an increase in ADP, Pi, Mg2+, H+ (lactic acid), and O2 free radicals lead to: 1.) Decrease in the rate of Ca2+ release, reuptake, and storage by the sarcoplasmic reticulum 2.) Decrease in the sensitivity of the thin filament proteins to activation by Ca2+ 3.) Direct inhibition of the binding and power-stroke motion of the myosin cross-bridges

Make flashcards of the information in Table 9.3 and describe the characteristics of the three skeletal muscle fiber types (highlighting differences between the mechanical, metabolic, and fatigue resistance properties of each fiber type).

Muscle fibers characterized by 1.) Maximal velocities of shortening 2.) Major pathway used to form ATP Slow oxidative (type 1) Fast oxidative-glycolytic (type 2A) Fast glycolytic (type 2X)

Draw and label fig 10.4 to show the components and functions of both a muscle spindle and a Golgi tendon organ. Where does this figure reside in relation to figure 9.2?

Muscle spindle - A connective-tissue capsule containing modified muscle fibers innervated by peripheral ends of afferent nerve fibers - These stretch receptors provide information about the length of a skeletal muscle Golgi tendon organ - The endings of afferent nerve fivers that wrap around collagen bundles in the tendons near their junction with the muscle - Senses the levels of tension present in a tendon

Reproduce Table 9.1, which enumerates the roles of ATP in skeletal muscle contraction

Na+/K+ ATPase pump maintains concentration gradients and allows action potential propagation Ca2+ ATPase pump in the sarcoplasmic reticulum actively transports Ca2+ into the reticulum, lowering cytosolic Ca2+ concentrations and ending the muscle contraction Myosin-ATPase energizes the cross-bridges, providing energy for muscle force generation Binding of ATP to myosin dissociates cross-bridges bound to actin, allowing repeated cross-bridge cycle

Using fig 11.23, describe the three-gland, three-hormone cascade, that depicts the regulated secretion of thyroid hormone and how negative feedback keeps everything in balance.

Neural inputs Hypothalamus (secretes TRH into portal vessel) Anterior pituitary (secretes TSH into circulation) Thyroid gland (secretes T3 and T4into circulation) Target cells (convert T3 to T4) -> respond to T3 Negative feedback of T3 and T4 on anterior pituitary and hypothalamus

Sequentially list and discuss the sequence of events between a motor neuron action potential and skeletal muscle fiber contraction (table 9.2)

Neuronal AP to fiber AP (1.) Action potential is initiated and propagates to motor neuron axon terminals (2.) Ca2+ enters axon terminals through voltage-gated Ca2+ channels (3.) Ca2+ entry triggers release of ACh from axon terminals (4.) ACh diffuses from axon terminals to motor end plate in muscle fiber (5.) ACh binds to nicotinic receptors on motor end plate, increasing their permeability to Na+ and K+ (6.) More Na+ moves into the fiber at the motor end plate than K+ moves out, depolarizing the membrane and producing the end-plate potential (EPP) (7.) Local currents depolarize the adjacent muscle cell plasma membrane to its threshold potential, generating an action potential that propagates over the muscle fiber surface and into the fiber along T-tubules EC-Coupling (8.) Action potential in T-tubules induces DHP receptors to pull open ryanodine receptor channels, allowing release of Ca2+ from terminal cisternae of sarcoplasmic reticulum (9.) Ca2+ binds to troponin on the thin filaments, causing tropomyosin to move away from its blocking position, thereby uncovering cross-bridge binding sites on actin Molecular tension (10.) Energized myosin cross-bridges on the thick filaments bind to actin: A + M-ADP-Pi --> A-M-ADP-Pi (11.) Cross-bridge binding triggers release of ATP hydrolysis products from myosin, producing an angular movement of each cross-bridge: A-M-ADP-Pi --> A-M + ADP + Pi (12.) ATP binds to myosin, breaking linkage between actin and myosin and thereby allowing cross-bridges to dissociate from actin: A-M + ATP --> A + M-ATP (13.) ATP bound to myosin is split, energizing the myosin cross-bridge: A + M-ATP --> A + M-ADP-Pi (14.) Cross-bridges repeat steps 10 to 13, producing movement (sliding) of thin filaments past thick filaments, Cycles of cross-bridge movement continue as long as Ca2+ remains bound to troponin Relaxation (15.) Cytosolic Ca2+ concentrations decrease as Ca2+-ATPase actively transports Ca2+ into sarcoplasmic reticulum (16.) Removal of Ca2+ from troponin restores blocking action of tropomyosin, the cross-bridge cycle ceases, and the muscle fiber relaxes

Using figure 12.15, draw a ventricular muscle cell action potential, explain the ionic events underlying its shape, and describe how changes in ion channel function can modify both electrical and mechanical function (e.g. L-type calcium channels)

No EPSP, No EPP Current from neighbor cell through gap junction The rapid opening of voltage gated Na+ channels is responsible for the rapid depolarization phase The prolonged plateau of depolarization is due to the slow but prolonged opening of voltage-gated Ca2+ channels (L-type = long lasting )

Use figs 9.13 and 9.14 to discuss the Sliding Filament Theory and how muscle shortening occurs.

No change in length of either the thick or thin filaments Thick filaments slide past overlapping thin filaments, results in shortening of the sarcomere (I band and H band are reduced)

Use fig 9.4 to draw and describe skeletal muscle sarcomeres, include all bands, lines, and zones.

One sarcomere is the region between two Z lines

Discuss and distinguish between the two kinds of spontaneous electrical activity in smooth muscle as shown in fig 9.36

Pacemaker potentials Cell's membrane potential oscillates to threshold and fires an AP spontaneously Slow waves Cell's membrane potential oscillates below the threshold potential An excitatory stimulus is required to fire action potentials (hormone, NT, paracrine substance) Inhibitory stimuli can also act to reduce the membrane potential

Using figure 12.12 and your lecture notes, thoroughly discuss the regulation of cardiac muscle via the autonomic nervous system. How does each branch affect heart rate and strength of contraction?

Parasympathetic - The vagus nerve releases ACh from varicosities which affect Muscarinic ACh receptors - Receptors located on the atria Sympathetic - Thoracic spinal nerves release NorEpi from varicosities - The adrenal medulla releases Epi (a neurohormone) into the blood stream - Epi and NorEpi influence B1 receptors on both the atria and ventricles Effects - Heart rate- Parasympathetic slows down; Sympathetic accelerates - Strength of contraction - parasympathetic weakens ONLY atria; sympathetic strengthens both atria and ventricles

Using an example (as in fig 11.10), define and illustrate what it means for a hormone to be permissive of another hormone.

Permissive effect - When the number of hormone receptors is influenced by the presence of another hormone Ex. Thyroid hormone is permissive of Epinephrine effects because Thyroid hormone increases the number of epinephrine receptors on target cells

Describe the Posterior pituitary gland. List its secretions; include the hormone's name, the abbreviation, its chemical class, and its major target/effect within the body.

Posterior Pituitary - an extension of hypothalamus neurons which synapse onto capillaries and release neurohormones Releases 2 peptide hormones ADH (vasopressin) - Acts on smooth muscle cells causing vasoconstriction -> increase in blood pressure - Acts within the kidneys to decrease water excretion, thereby retaining fluid in the body (maintenance of blood volume) Oxytocin - Stimulates contraction of smooth muscles cells in the breasts which results in milk ejection during lactation - Stretch receptors in cervix cause positive feedback -> contraction of smooth muscles in uterus during labor

Using section 11.15, discuss Adrenal Insufficiency, highlighting symptoms, causes, and diagnostic hormone profiles.

Primary adrenal insufficiency (Addison's disease) - Problem with the adrenal gland (destructive tumors, infection, auto-immune destruction) - May effect all zones of the adrenal cortex (cortisol and aldosterone) Symptoms Hypotension, hypoglycemia, high plasma ACTH Secondary adrenal insufficiency - Loss or low ACTH in plasma (problem with anterior pituitary gland tropic hormone) Symptoms (same but less dramatic) Hypotension, hypoglycemia

Reproduce figure 9.6 and describe the relevant membrane structures in skeletal muscle fibers.

Sarcolemma - Composed of the plasma membrane and continuous t tubules. Allows for action potentials to travel throughout the interior of the muscle fiber (via t-tubules) Sarcoplasmic reticulum - Contains terminal cisternae which are connected via a series of smaller tubular elements. Allows for the storage of large quantities of Ca2+

Draw fig 17.9 and discuss the human male testis anatomy.

Seminiferous tubules -> efferent ductules -> vas deferens

Describe the purpose and function of the Sertoli cells

Sertoli cells ("nurse") Extend from basement membrane to lumen in the center of the tubule Are joined to adjacent Sertoli cells by tight junctions Functions 1.) Provide Sertoli cell barrier to chemicals in the plasma 2.) Nourish developing sperm 3.) Secrete luminal fluid, including androgen-binding protein 4.) Respond to stimulation by testosterone and FSH to secrete paracrine agents that stimulate sperm proliferation and differentiation 5.) Secrete the protein hormone inhibin, which inhibits FSH secretion from the pituitary gland 6.) Secrete paracrine agents that influence the function of Leydig cells 7.) Phagocytize defective sperm 8.) Secrete Anti-Müllerian hormone (AMH), which causes the primordial female duct system to regress during embryonic development

Using fig 11.20, differentiate between short-loop and long-loop negative feedback

Short loop Exerted by the anterior pituitary gland hormone on the hypothalamus Long loop Exerted on the hypothalamus and/or anterior pituitary gland by the third hormone in the sequence

Describe and contrast the growth abnormalities of short stature, gigantism, and acromegaly.

Short stature a.) Decreased GH (and therefore decreased IGF-1) b.) Insensitive GH receptors c.) Lack of IGF-1 secretion (GH normal) d.) Insensitive IGF-1 receptors Acromegaly - Too much GH after epiphyseal plates close Gigantism - Too much GH before epiphyseal plates close An individual can have both acromegaly and gigantism They are caused by tumors which hyper-secrete GH

Explain why the latent period is different when comparing isometric to isotonic contractions.

Shortening does not begin until enough cross bridges have attached and muscle tension exceeds the load on the fiber The heavier the load, the longer it takes for tension to increase to the value of the load when shortening will begin Eventually a load is reached that the fiber is unable to lift, the velocity and distance of shortening then decrease to zero, and the contraction becomes completely isometric

Use fig 9.1 to list and describe the distinguishing features of the three major muscle types.

Skeletal muscle - Striated, rods - Multi-nucleated Cardiac muscle - Striated, rods - Mono-nucleated Smooth muscle - No striations, spindle - Mono-nucleated

Describe smooth molecular architecture and contrast this with skeletal muscle; utilize figs 9.1, 9.32, 9.33, and table 9.6.

Smooth muscle structure - Spindle-shaped (not rods/cylinders) - 2-10 um in diameter, 50-400 um in length - Single nucleus - Generally interconnected - forms sheets - No T-tubules - No troponin (but tropomyosin present!) - Unstriated (no sarcomeres, no Z lines) - Poorly developed SR - Rely on Ca2+ from both inside and outside the cell - Contain dense bodies (Z line function) - Innervated by the autonomic division of the PNS (both sympathetic and parasympathetic)

Reproduce the fiber length-tension relationship in Fig 9.21 and explain the changes in both active force and passive force at different fiber lengths.

Springlike characteristic of titin (attaches Z line to thick filament) is responsible for most of the passive elastic properties of muscle fibers - Passive force increases as a muscle is stretched Amount of active tension developed during contraction depends on the length of the fiber - Muscle fibers have an optimal length (L0), lengths above and below L0 result in less than maximum tetanic tension

Use fig 11.20 to draw a generic figure that illustrates and defines both negative feedback and the tropic and trophic actions of hormones in multi-gland (e.g. 3-gland cascades).

Stimulus -> Hypothalamus secretes hormone into portal vessel -> Anterior pituitary secretes hormone -> 3rd endocrine gland releases a hormone -> target cells respond to hormone 3

Make a list of the functions for cortisol in the stressed conditions; provide rationales for all these secretions when they occur.

Stress levels 1.) Metabolic effects (glucose sparing), mobilize glucose, fatty acids, amino acids (for fuel and tissue repair) - Muscle loss and diabetes if prolonged exposure 2.) Bone reabsorption (Ca2+ mobilization) repair bone breaks - Osteoporosis if prolonged exposure 3.) Support sympathetic responses (fight, flight) Keep MAP up - High blood pressure if prolonged exposure 4.) Stimulates erythropoietin (replace RBCs if blood loss) - Polycythemia if prolonged exposure 5.) Anti-inflammatory/immunosuppression - Useful for preventing rejection of transplanted organs 6.) Psychological/analgesic - Elevates mood - Endorphins co-released w ACTH; inhibit pain 7.) Inhibition of non-essential functions: reproduction/growth

Sketch fig 9.20 and explain the summation of tension from multiple stimuli; then contrast unfused from fused tetanus data.

Summation - The increase in muscle tension from successive action potentials occurring during the phase of mechanical activity Tetanus - A maintained contraction in response to repetitive stimulation Unfused tetanus - Lower stimulation frequencies, muscle fiber partially relaxes in between stimuli Fused tetanus - Higher stimulation frequencies, no oscillations in tension

Describe the structure thyroid hormone, distinguishing between T3 and T4.

T4 - Thyroxine - 90% of secretion - "Storage pool" in blood - Converted to T3 in target cells T3 - Triiodothyronine - Most active, potent form

Use figs 11.14 and 11.17 to draw & describe the hypothalamus-pituitary relationship. Carefully depict the two types of connection between the hypothalamus and the pituitary gland.

The pituitary gland (composed of anterior and posterior lobes) is connected to the hypothalamus by the infundibulum Posterior pituitary The axons of hypothalamic neurons pass down the infundibulum ending within the posterior pituitary - Hormones are synthesized in the hypothalamus before transport to axon terminals of the posterior pituitary - Action potentials propagate from hypothalamus to posterior lobe terminals and trigger exocytosis of neurohormones Anterior pituitary The median eminence (junction between the hypothalamus and the infundibulum) contains capillaries which combine to form the hypothalamo-hypophyseal portal vessels which pass down the infundibulum to the anterior pituitary gland -Portal vessel arrangement: (Arteriole -> Median eminence -> Hypothalamo-hypophyseal portal vessel -> AP gland capillaries -> Venule) - Hypophysiotropic hormones released into the term-13median eminence travel through the portal vessel in the infundibulum to endocrine cells in the anterior pituitary

Use figures 12.20 and 9.41 to explain the significance of the cardiac action potential duration.

The prolonged depolarization delays Na+ and Ca2+ channel recovery from inactivation The prolonged refractory period of cardiac muscle prevents tetanus and allows time for ventricles to fill with blood prior to pumping

Draw fig 17.23 and explain the control of estrogen synthesis during the early and middle parts of the follicular phase.

Theca cells produce androgens which diffuse to Granulosa cells which convert androgens to estrogen

Draw fig 9.3 and describe the structural and functional differences between muscle myosin and actin.

Thick filaments - Each myosin molecule contains a long rod-like segment facing the center of the sarcomere and two cross bridge heads which extend out towards the overlying actin - Each cross- bridge head has two binding sites - one for actin and one for ATP; the ATP binding site also serves as an enzyme that hydrolyzes ATP Thin filaments - Composed of G-actin (globular) assembled into a helix (F-actin) - Tropomyosin strands block myosin binding sites on F-actin - Troponin pushes tropomyosin onto F-actin

Reproduce both parts of fig 9.16a and explain the isometric twitch events and data.

Twitch - The mechanical response of a muscle fiber to a single action potential Isometric: no change in length Latent period - Time following the action potential before tension in the muscle fiber begins to increase Contraction time - Time interval from the beginning of tension development to the peak tension Fast twitch fibers - Contraction time ~ 10 msec Slow twitch fibers - Contract time ~ 100 msec

Using figs 9.27, 9.29, and 9.30, discuss the lever action of muscles; be able to calculate forces and movement velocities as the lever distances change.

Weight x Distance from joint = Muscle force x distance between joint and insertion

Using fig 11.21, draw and describe the thyroid gland's histology.

Within the thyroid gland are numerous follicles, each composed of an enclosed sphere of epithelial cells surrounding a core containing a protein rich material called colloid