Chapter 16: The Endocrine System

Syndrome of inappropriate ADH secretion (SIADH)

(SIADH) can occur in -Patients with meningitis -With a hypothalamic injury -In people with small-cell carcinoma of the lung -It is marked by the retention of fluid, headache, disorientation due to brain edema -Treatment includes fluid restriction; blood sodium level monitoring and diuretics (furosemide) to decrease reabsorption of water

Hyperparathyroidism

(excess PTH) is due to parathyroid gland tumor -Calcium leaches from bones, causing them to soften and deform -Elevated Ca2+ depresses nervous system leading to weak skeletal muscles ^osteoporosis -Excess Ca2+ precipitate in the kidney tubules leading to the formation of kidney stones ^kidney stones -Osteitis fibrosa cystica: severe form resulting in easily fractured bones

Summary of Regulation and effects

*chart*

Anterior Pituitary Hormones - GH

*diagram*

In addition hormone can regulate target cells by being able to:

-Alter plasma membrane permeability and/or membrane potential by opening or closing ion channels -Stimulate synthesis of enzymes or other proteins -Activate or deactivate enzymes -Induce secretory activity -Stimulate mitosis

Insulin also Triggers cells to

-Catalyze oxidation of glucose for ATP production: first priority -Polymerize glucose to form glycogen -Convert glucose to fat (particularly in adipose tissue)

Hyperinsulinism

-Excessive insulin secretion -Causes hypoglycemia: low blood glucose levels -Symptoms: anxiety, nervousness, disorientation, unconsciousness, even death -Treatment: sugar ingestion

PIP2-calcium signaling mechanism

-Hormone-activated G protein activates a different effector enzyme: phospholipase C -Activated phospholipase (second messenger-enzyme) C splits membrane protein, PIP2, into two second messengers: 1.Diacylglycerol (DAG) activates protein kinases (PKC) (enzyme that adds substrate groups onto its substrate) 2.Inositol trisphosphate (IP3) causes Ca2+ release from intracellular storage sites -so then it travels to the ER and and causes it to release its calcium ^ER is also responsible for housing/storing calcium >release calmodulin, which binds to calcium and then interacts with a downstream kinase to allow with the phosphorylation of myosin to then interact with the actin filament, just one example

Ligand

-Ligand-travels through the blood stream from the cell receptor; must interact with a cell with corresponding cell receptor and then signal transduction occurs (chemical reaction) 1. ligand/hormone 2. receptor must be present, or nothing happens

Oxytocin in Love

-Neurotransmitter in the brain that has been linked to regulation of emotional, cognitive, and social behaviors -One important component of a complex neurochemical system that allows the body to adapt to highly emotive situations -In both genders, sexual activity stimulates the release of oxytocin, which has a role in erection and orgasm. -In women, it has been proposed that the increased uterine motility may help sperm to reach their destination -Oxytocin also reduces stress responses, including anxiety - also reduces stress/anxiety

Endocrine system controls and integrates

-Reproduction -Growth and development -Maintenance of electrolyte, water, and nutrient balance of blood -Regulation of cellular metabolism and energy balance -Mobilization of body defenses *responsible for the influences on other systems: reproductive, orthopedic growth, electrolyte regulation (kidneys), cellular metabolism

Hormones have different response times

-Some responses are immediate -Some, especially steroid, can take hours to days -Some are inactive until they enter target cells The duration of response is usually limited -Ranges from 10 seconds to several hours -Effects may disappear rapidly as blood levels drop, but some may persist for hours at low blood levels Half-life, onset, and duration of hormone activity are dependent on whether the hormone is water (short) or lipid (longer) soluble

Adrenal Cortex

-This area of adrenal gland produces over 24 different hormones collectively called corticosteroids -Steroid hormones are not stored in cells and the rate of release depends on rate of synthesis Three layers of cortical cells produce the different corticosteroids 1. Zona glomerulosa—Mineralocorticoids control concentration of minerals and water in the blood 2. Zona fasciculata—Glucocorticoids 3. Zona reticularis—Gonadocorticoids -Produce adrenal sex hormones

Capillary Beds (Capillary Plexus)

-connect one arteriole and one venule -precapillary sphincter -guards entrance to each capillary -opens and closes, causing capillary blood to flow in pulses -inherently leaky so that can interact with external environment and exchanging material the type of hormones also being released in the secondary plexus will tell you (later) about why they need to be stored and - upon signaling - stimulated to move out

Pituitary Hypothalamic Relationships: Anterior Lobe

1. Anterior lobe is glandular tissue derived epithelial tissue from an outpocketing of oral mucosa 2. It contacts the posterior lobe at the neurohypophysis -There is NO direct neural connection with the hypothalamus -Vascularly connected to hypothalamus via hypophyseal portal system consisting of: a. Primary capillary plexus (bed)- where ion exchange happens b. Hypophyseal portal veins c. Secondary capillary plexus-releases hormones -This system unique in that it has bloods vessels that feed a capillary system that flows to a vein that feed a secondary capillary bed

Hormone Release

1. Blood levels of hormones -Controlled by negative feedback systems ^Increased hormone effects on target cells result in the inhibition of further hormone release This levels of control maintains levels in a narrow, desirable range 2. Hormone release is triggered by Endocrine gland stimuli Nervous system modulation 3. Endocrine glands are stimulated to synthesize and release hormones in response to one of three stimuli: -Humoral stimuli -Neural stimuli -Hormonal stimuli ie: negative feedback the end result shuts of cycle to the original positive end result goes back and creates original stimulus

Indirect actions on growth

1. GH triggers liver, skeletal muscle, and bone to produce insulin-like growth factors (IGFs) 2. In the liver, skeletal muscle, and bone produce IGF in response to GH (think synergism) 3. IGFs stimulate: -Cellular uptake of nutrients used to synthesize DNA and proteins needed for cell division -Formation of collagen and deposition of bone matrix -GH stimulates most cells to enlarge and divide, but major targets are bone (via the epiphyseal plate) and skeletal muscle

Anterior Pituitary Hormones - FSH and LH

1. Gonadotropins (FSH and LH) 2. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are secreted by gonadotropic cells of anterior pituitary 3. In either sex FSH stimulates production of gametes (egg or sperm) 4. LH promotes production of gonadal hormones -In females, LH helps mature follicles of egg, triggers ovulation and release of estrogen and progesterone -In males, LH stimulates production of testosterone 5. LH and FSH both are absent from blood in prepubertal boys and girls -Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty -Suppressed by gonadal hormones (feedback)

Growth Hormone

1. Growth hormone (GH) -Called somatotropin since it is produced by somatotropic cells -It is anabolic (to build) that has direct actions on metabolism and indirect growth-promoting actions 2. Direct actions on metabolism -Mobilizes fat and increases blood levels of fatty acids for use as fuel and encourages cellular protein synthesis *beta oxidation- 1. have hydrocarbon chains with phosphate heads 2. have Glycolysis, which glucose go through, but proteins and fats bypass glycolysis and enter into citric acid cycle 3. then, in beta oxidation, the long hydrocarbon chain gets processed in the citric acid cycle 2 carbons at a time Cellular respiration= Glycolysis, citric acid cycle, electron transport chain 3. Anti insulin effect: -insulin gets released in the pancreas via beta cells; lowering the level of glucose -Decreases the rate of cellular glucose uptake thus conserving glucose; stored in glucogen in muscles and liver -Triggers liver to break down glycogen into glucose, releases glucose into the blood raising blood glucose levels Increases cellular amino acid uptake and protein production

Cyclic AMP (cAMP) signaling mechanism

1. Hormone (first messenger) binds to receptor 2. Receptor activates a G protein -Ligand binding causes the receptor to change shape -Guanosine diphosphate (GDP) is replaced with GTP (triphosphate-high energy) -GDP is the inactive state GTP is the active state. (GDP- diphosphate; low energy) 3. G protein activates or inhibits effector enzyme adenylate cyclase (ENZYME) -Gs stimulate while Gi inhibit -Once bound the G protein to adenylate cyclase the GTP is hydrolyzed to and GDP 4. Adenylate cyclase then converts ATP to cAMP (second messenger) -one of the G subunits cleaved activates the cyclase enzyme and then cyclizes the ATP into cAMP 5. cAMP activates protein kinases that phosphorylates other proteins -Phosphorylated proteins are then either activated or inactivated -cAMP is rapidly degraded by enzyme phosphodiesterase, stopping cascade -Cascades have huge amplification effect

Half-Life, Onset, and Duration of Hormone Activity

1. Hormones circulate in blood in two forms - free or bound to a protein carrier -Steroids and thyroid hormone are attached to plasma proteins -All others circulate without carriers 2. Concentration of circulating hormone in a system reflects: a. Rate of release b. Speed at which it is inactivated and removed from body 3. Hormones can be removed from blood by: -Degrading enzymes in the target cell -Most are removed by the kidneys or liver where the degraded products are excreted -hormones will be inactivated at some point through the system by enzymes located in the liver, which break down, degrade, and process hormones before the kidney excrete them (remember detoxifying) 4. Half-life: time required for level of hormone in blood level to decrease by half (the amount of time it takes for half of the hormone to be released from the blood) -Varies anywhere from fraction of a minute to a week, depending on hormone ie: when you stop medication, need to wait at least 2 weeks before going back on do that you can return to the baseline

Homeostatic Imbalance

1. Hypersecretion 2. Hyposecretion

Glucocorticoids

1. Influence metabolism of most cells and help us resist stressors 2. Keep blood glucose levels relatively constant in between meals 3. Maintain blood pressure by increasing action of vasoconstrictors 4. Glucocorticoid hormones include: -Cortisol (hydrocortisone); only glucocorticoid in significant amounts in humans -Cortisone -Corticosterone

Three cardinal signs of DM

1. Polyuria: huge urine output -Glucose acts as osmotic diuretic 2. Polydipsia: excessive thirst From water loss due to polyuria 3. Polyphagia: excessive hunger and food consumption -Cells cannot take up glucose and are "starving"

Anterior Pituitary Hormones

1. Produced six hormones all of which are peptide hormones 2. When a chemical signal is received from the hypothalamus the AP releases one or a combination of the six hormones 3. All but growth hormone (GH) activate target cells via cAMP second-messenger system and received and regulated by hypothalamus -Growth hormone (GH) -Thyroid-stimulating hormone (TSH) (tropic) -Adrenocorticotropic hormone (ACTH) (tropic) -Follicle-stimulating hormone (FSH) (tropic) -Luteinizing hormone (LH) (tropic) -Prolactin (PRL) Everything but GH are going to be regulated by cAMP

Anterior Pituitary Hormones - PRL

1. Prolactin (PRL) is secreted by prolactin cells of anterior pituitary -Stimulates milk production in females; role in males not well understood 2. Unlike the other AP hormones PRL is controlled by an inhibitory hormone identified as prolactin-inhibiting hormone (PIH), which is dopamine -PIH prevents release of PRL until needed, with decreased levels leading to lactation -PRL levels rise and fall in rhythm with the levels of estrogen in the blood -Increased estrogen levels stimulate PRL -There is a short and brief increase in PRL levels before a menstrual cycle ^Reason behind breast swelling and tenderness 3. During Pregnancy PRL blood levels rise toward end -stay low until after the pregnancy 4. Suckling stimulates PRL release and promotes continued milk production -some women dont produce due to low levels of prolactin and insufficiency in cell production

Regulation of ACTH

1. Regulation of ACTH release is caused by hypothalamic corticotropin-releasing hormone (CRH) in daily rhythm -Vasopressin also regulates release of ACTH 2. ACTH enters the blood stream and signals the adrenal cortex to produce cortisol from cholesterol. 3. Cortisol from the adrenal cortex will negatively regulate both the hypothalamus and the pituitary gland -Decreases the secretion of CRH and vasopressin -Directly reduces the cleavage of proopiomelanocortin (POMC) into ACTH and β-endorphins.

Pituitary Hypothalamic Relationships: Posterior lobe

1. The Posterior lobe is neural tissue derived from a down growth of brain -Maintains neural connection to hypothalamus via hypothalamic-hypophyseal tract -Tract arises from neurons in paraventricular and supraoptic nuclei in hypothalamus and runs via the infundibulum -when one of these nerves gets stimulated, then one is responsible for the release of of ADH (antidiuretuc hormone) and oxytocin from its synaptic terminus -stores in synaptic terminal and the.n when stimulated, release hormone into the systemic circulation 2. Secretes two neurohormones (oxytocin and ADH) -Hormones are stored in axon terminals in posterior pituitary and are released into blood when neurons fire Released into the capillary bed in the posterior pituitary for systemic distribution

Thyroid-stimulating hormone (TSH) aka thyrotropin

1. Tropic hormone that stimulates normal development and secretory activity of thyroid -Results on the thyroid producing thyroxine (T4), and then triiodothyronine (T3) that regulate the metabolism of tissues in the body. 2. TSH is secreted from the thyrotrophic cells in anterior pituitary when another hormone called thyrotropin-releasing hormone (TRH) is released from the hypothalamus -TSH is inhibited by rising blood levels of thyroid hormones that act on both pituitary and hypothalamus Also inhibited by GHIH

Growth hormone Targets

1. fat cells -beta oxidation 2. bone cells 3. muscle cells 4. immune cells 5. hits the liver -then releases insulin growth factor -then IGF works with GH to build bone and muscle -as IGF starts to build it goes back to shut off GHRH in spec way (not tropic) by making Growth hormone inhibiting hormone to shut off GHRH at the anterior pituitary

Anterior Pituitary Hormone-GH

1`. Bone 2. Metabolism 3. Linear Growth 4. Muscle 5. Adipose Tissue -bone and muscle work toegther for body to move; ^ metabolic activity ^size of muscle cells

negative feedback loop

A feedback loop that causes a system to change in the opposite direction from which it is moving

G-protein coupled receptors

A special class of membrane receptors with an associated GTP binding protein; activation of a G protein-coupled receptor involves dissociation and GTP hydrolysis -Possibly G standing for glutamine -all have 7 transmembrane domains- meaning that the G-protein couple receptors characterize the receptors ^passes through membrane 7 times; all G proteins are responsible for the signal -non-steroidal water based binding to the surface of a protein receptor -it's more 3 dimensional and across the WHOLE membrane turning on; allows one ligand to have reaction occur, then G protein stays on the whole time allowing system to stay on for long periods of time

Anterior Pituitary

A true endocrine gland because produces AND releases (adenohypophysis) consists of glandular tissue Produces and releases hormones

Adipose Cells

Adipose cells (leptin), thymus (thymic hormone) , and cells in walls of small intestine, stomach, kidneys, and heart

Action of Hormones

All major hormones circulate systemically throughout the body, however only cells with receptors for that hormone are affected -not every cell will have the receptors on the cell surfaces (like group texting-not sending to everyone; just the 3 contacts) => works because ligand receptor interaction Target cells: cells or tissues with receptors for a specific hormone 1. synergism 2. permissive 3. antagonistic

Two main classes of hormones

Amino acid-based hormones and steroids Amino acid-based hormones Amino acid derivatives, peptides, and proteins -bind on cell surface Steroids Synthesized from cholesterol Gonadal and adrenocortical hormones are the only two produced by the major endocrine glands. (amphitheatric- bind to nuclear based receptor on the inside of the cell=> interacting with the nuclear membrane -bind/directly interact with receptors found in the nucleus due to cholesterol if its charged it cannot cross the membrane

Plasma Membrane Receptors and Second-Messenger Systems

Amino acid-based hormones, except thyroid hormone, exert effects through second-messenger systems Two main second-messenger systems: Cyclic AMP or cAMP PIP2-calcium

Up/Down Regulation

Amount of hormone can influence number of receptors for that hormone 1. Up-regulation: target cells form more receptors in response to low hormone levels (permissiveness) -Making more receptors 2. Down-regulation: target cells lose receptors in response to high hormone levels -Desensitizes the target cells to prevent them from overreacting to persistently high levels of hormone ^loses some receptors and then less effective ie being addicted to caffeine, eventually you need more because the cell down regulates the receptors on cell surface and build up tolerance when down reg stops go backs to baseline

Antagonism

Antagonism happens when one hormone produces the opposite effects of another hormone; this is used to "fine tune" the activity of target cells with great accuracy. insulin and glucagon Most hormones have primary effects that directly regulate target cells. -when something gets to high or low, antagonist hormones regulate homeostasis -Ying and Yang -similar to the negative feedback (go from high to low to maintain homeostasis)

Antidiuretic hormone

Antidiuretic - substance that prevent urine formation Antidiuretic hormone (ADH) - functions to retain water in the body and to constrict blood vessels -results in an increase in BP -by regulating the solute, it allows the receptors to monitor bp receptors ^if concentration of solute gets too high, youre going to release antidiuretic hormone ADH increases water reabsorption in the kidney's collecting ducts or nephrons ^maintain bp *alcohol blocks/inhibits release of ADH -Hypothalamus contains osmoreceptors that monitor solute concentrations in the blood -If concentration too high, posterior pituitary triggered to secrete ADH -Targets kidney tubules via cAMP to reabsorb more water into the blood to inhibit or prevent urine formation -Solute concentration of the blood declines -Release also triggered by pain, low blood pressure, and drugs (nicotine and morphine) Consumption of alcohol inhibits ADH secretion and results in increased urine production Diuretic drugs block ADH and flush water from the body Used to manage hypertension and edema typical associated with congestive heart failure

Thyroid Hormone-T3, T4

Body's major metabolic hormone Found in two forms 1. T3 2. T4

Receptors of T3 and T4

Both T4 and T3 can bind cell surface receptors but T3 does so at a much higher affinity Conversion of T4 to T3 is regulated by 5' deiodinase that remove one iodine from T4 Exposure to the cold stimulates THR that ultimately increases body metabolism and heat production TSH can be inhibited by GHIH, dopamine, corticosteroids TH release can be inhibited by high iodide blood levels

Thyroid Gland

Butterfly-shaped gland in anterior neck on the trachea, just inferior to larynx, that consists of: Isthmus: median mass connecting two lateral lobes Largest of the endocrine glands Extensive blood supply from the superior and inferior arteries (the dividing line of superior and inferior is the diaphragm) superior- above inferior- below

Homeostatic Imbalance DM

Diabetes mellitus (DM) can be due to: -Hyposecretion of insulin: Type 1 -Hypoactivity of insulin: Type 2 When blood glucose levels remain high, person feels nauseated, leading to sympathetic response ^Fight-or-flight response acts to further increase blood glucose levels Glycosuria: excess glucose is spilled into urine

Synergism

Different hormone-receptor interactions produce different regulatory changes within the target cell through chemical reactions -2 hormones that work more efficiently together (effects much more dramatic together) Synergism - more than one hormone produces same effects on target cell, causing amplification (Gestalt) 1. Glucagon and epinephrine both cause liver to release glucose at a greater rate if each had acted alone ^helps maintain blood sugar levels during fasting states ^Glucagon breaks down glycogen to maintain blood glucose and then glucose goes into blood stream 2. Epinephrine (adrenaline) is released from nerve endings and the adrenals, and acts directly on the liver to promote sugar production via glycogenolysis (causes all of glucose to massively increase in blood stream) ex./ could be 350 nondiabetic when afraid 3. Epinephrine also promotes the breakdown and release of fat nutrients that travel to the liver and that are converted into sugar and ketones.

Permissiveness

Different hormone-receptor interactions produce different regulatory changes within the target cell through chemical reactions Permissiveness occurs when a small amount of one hormone allows a second one to have its full effects on a target cell. Thyroid hormone increases the number of receptors available for epinephrine and increases epinephrine's effect ^will prime for other mechanisms to occur-for hormones to take full effect on cell -have receptor on the surface of the cell, ligand binds, and initiates signal transmission pathway, then the protein allows for more receptors to decorate the surface, then allowing more receptors to decorate the cell, and then creating more docking sites for the ligands to bind -after signal transmission pathway greats more receptors on the cell surface to make it easier for the hormones to find the target cell

Factors that influence insulin release

Elevated blood glucose levels: primary stimulus Rising blood levels of amino acids and fatty acids Release of acetylcholine by parasympathetic nerve fibers Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids Somatostatin and sympathetic nervous system inhibit insulin release

Types of Endocrine Glands

Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands Some have exocrine and endocrine functions Pancreas, gonads, placenta Other tissues and organs that contain endocrine cells and produce hormones *Majority of regulations comes from the pituitary- release hormones that systemically travel throughout the body*

Endocrine System

Endocrine system acts with nervous system to coordinate and integrate activity of body cells Influences metabolic activities using hormones transported in blood -help regulate metabolic rate -process chemical reactions of the body (catabolism-breakdown; anabolism- build up)

Thyroid Hormone

Enters target cell and binds to intracellular receptors within nucleus Triggers transcription of various metabolic genes Effects of thyroid hormone include: Increases basal metabolic rate and heat production by regulating genes dealing with glucose oxidation Referred to as calorigenic effect Regulates tissue growth and development Critical for normal skeletal and nervous system development and reproductive capabilities Maintains blood pressure Increases adrenergic receptors in blood vessels (vasoconstrition/Vasodialation)

Exocrine glands vs Endocrine glands

Exocrine: --ducts secrete products onto epithelial surface Endocrine: --Ductless --Cells secrete products into interstitial fluid and bloodstream Exocrine glands Produce nonhormonal substances (examples: sweat, saliva) Have ducts to carry secretion to membrane surface Endocrine glands Produce hormones Lack ducts Release their hormones into tissue fluid

Glucagon

Extremely potent hyperglycemic agent -Triggered by decreased blood glucose levels, rising amino acid levels, or sympathetic nervous system -Glucagon functions to raise blood glucose levels by targeting liver to: 1. Break down glycogen into glucose -Glycogenolysis 2. Synthesize glucose from lactic acid and other noncarbohydrates Gluconeogenesis 3. Release glucose into blood which causes blood glucose to increase *Insulin drops, Glucagon goes up ye

follicles of thyroid gland

Follicles: hollow sphere of epithelial follicular cells that produce glycoprotein thyroglobulin (think cellular warehouse) The central cavity of follicles stores colloid -Amber colored material composed to thyroglobulin with iodine molecules -Thyroid Hormone is derived from colloid Perifollicular cells - produce calcitonin

Parathyroid Gland

Four to eight tiny yellow-brown glands embedded in posterior aspect of thyroid Contain parathyroid cells that secrete parathyroid hormone (PTH), or parathormone PTH is most important hormone in blood Ca2+ homeostasis -Secreted in response to low blood levels of Ca2+ Inhibited by rising levels of Ca2+ -Target organs are skeleton, kidneys, and intestine Functions to: 1. Stimulate osteoclasts to digest bone matrix and release Ca2+ to blood 2. Enhances reabsorption of Ca2+ and secretion of phosphate (PO43-) by kidneys 3. Promotes activation of vitamin D by kidneys, which leads to increased absorption of Ca2+ by intestinal mucosa

Ghrelin

Ghrelin (hunger hormone) also stimulates GH release GHIH release is controlled by the feedback of GH and IGFs High HG levels also inhibit its own release Note the total amount of GH daily secreted is high during adolescence and declines with age ^GH at later age = ^ cancer (^cell division = ^ DNA) -High levels of GH will also target its own inhibition

Thymus

Gland in the thoracic cavity above the heart where T lymphocytes mature.

Specific Hormonal Stimuli

Hormonal stimuli - Hormones stimulate other endocrine organs to release their hormones 1. Hypothalamic hormones stimulate release of most anterior pituitary hormones 2. Anterior pituitary hormones stimulate targets to secrete still more hormones 3. Hypothalamic-pituitary-target endocrine organ feedback loop -Hormones from final target organs inhibit release of anterior pituitary hormones -negative feedback, will go back and shut off the original stimuli

Composition of Hormones and Receptor Interactions

Hormones act in one of two ways, depending on their chemical nature and receptor location 1. Water-soluble hormones (all amino acid-based hormones except thyroid hormone) Act on plasma membrane receptors Act via G protein second messengers Cannot enter cell *associated with some sort of charge* -most AA hormones, except T3, are h20 soluble -cannot freely cross through membrane, bind to receptor at the cell surface to initiate transduction potential 2. Lipid-soluble hormones (steroid and thyroid hormones-exception to the rule) Act on intracellular receptors that directly activate genes Can enter cell -then bind/interact with receptors on/ in the nuclear envelope ^in the nuc envelope activate translation or transduction of genes => transactivation: any transcription factor binding to the promoter that then makes mRNA->RNA-> Protein

Chemical Classification of Hormones

Hormones: Steroids-cholesterol Nonsteroidal hormones -proteins -glycoproteins -peptides -Amino Acid Derivatives

growth plates

Human growth hormone causes bones to grow at these locations closes at 20-21

Humoral Stimuli

Humoral stimuli - endocrine glands secrete hormones in direct response to changing blood levels of ions and nutrients Parathyroid Gland and Ca2+ in the blood Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone) -then the bone will release calcium (osteoclast) -also mobilize intercellular calcium levels in the intestines -blocks exit of calcium from the kidneys through the utterers (calcium retention) PTH causes Ca2+ concentrations to rise, and stimulus is removed when the calcium levels are too high the thyroid and parathyroid work together to keep normal ^Thyroid then releases calcitonin to stimulate the kidney to release calcium from osteoblasts through the urine

Hypersecretion

Hypersecretion of GH is usually caused by anterior pituitary tumor -In children results in gigantism Can reach heights of 8 feet In adults results in acromegaly -Overgrowth of hands, feet, and face

Homeostatic Imbalance Glucocorticoids

Hypersecretion—Cushing's syndrome/disease (deregulation in the immune system) 1. Depresses cartilage/bone formation and immune system; inhibits inflammation; disrupts neural, cardiovascular, and gastrointestinal function 2. Causes: tumor on pituitary, lungs, pancreas, kidney, or adrenal cortex; overuse of corticosteroids 3. Cushingoid signs: "moon" face and "buffalo hump" Treatment: removal of tumor, discontinuation of drugs Hyposecretion—Addison's disease 1. Also involves deficits in mineralocorticoids 2. Decrease in glucose and Na+ levels 3. Weight loss, severe dehydration, and hypotension 4. Treatment: corticosteroid replacement therapy *where salt goes water follows*

Hyposecretion

Hyposecretion of GH In children results in pituitary dwarfism -May reach height of only 4 feet -In adults usually causes no problems

The hypothalamus and the Pituitary

Hypothalamus is connected to pituitary gland (hypophysis) via stalk called infundibulum (anterior and posterior pituitary; and sheath that connects th pathway from pituitary to the hypothalamus- Infundibulum) -region in the lower brain are responsible for the primal not intuitive/cognitive actions ie: breathing

Hypothalamus

Hypothalamus produces and releases hormones but also has neural functions. This make it an neuroendocrine organ

releasing and inhibiting hormones

Hypothalamus secretes releasing and inhibiting hormones to anterior pituitary to regulate hormone secretion Ensures that small amounts of hormones from the hypothalamus get to the anterior pituitary quickly and undiluted

Insulin

Insulin - two amino acid chains linked together by disulfide bonds It is made as proinsulin that is systematically cleaved to the mature form in a secretory vesicle in the beta cell Secreted when blood glucose levels increase Insulin functions to lower blood glucose levels in three ways: -Enhances membrane transport of glucose into fat and muscle cells Inhibits breakdown of glycogen to glucose Inhibits conversion of amino acids or fats to glucose -Binds to tyrosine kinase enzyme receptor triggers cell to increase glucose uptake

Intracellular Receptors and Direct Gene Activation

Lipid-soluble steroid hormones and thyroid hormone can diffuse into target cells and bind with intracellular receptors Receptor-hormone complex enters nucleus and binds to specific region of DNA Helps initiate DNA transcription to produce mRNA mRNA is then translated into specific protein Proteins synthesized have various functions Examples: metabolic activities, structural purposes, or exported from cell *Steroid based hormones can act as a subunit in transcription->translation-> protein synthesis

Homeostatic Imbalance Diabetes insipidus (overflow tasteless)

Marked by intense thirst and urine output ADH deficiency due to damage to hypothalamus or posterior pituitary Must keep well hydrated There is no effective treatment for dipsogenic DI, which is caused by a defect in the thirst mechanism.

Capillaries

Microscopic vessel through which exchanges take place between the blood and cells of the body -contains arteries and veins Arteries branch off delivering oxygenated blood -The wall of the capillary have these things called fenestrations (clefts that allow things to exit out of the tube to the oxygen needing cells) -get material to exit out through capillary beds (gaps) and interact with the cell ^endocrine cells- hormones go to a target organs receptor cite by entering into the blood stream thru cap beds to go to pituitary and then go where they need to go in the body

To make action work....

Most hormones have primary effects that directly regulate target cells. The specific response depends on the target cell type Epinephrine Actions vary by tissue type and by the differing responses of the various receptor sites scattered throughout the body. Causes smooth muscle relaxation in the airways, but causes contraction of the smooth muscle that lines most arterioles. ie: causes heart to increase and for liver to increase the level of glucose metabolism -causes vasodilation for everything to pump faster -intestinal mobility -by releasing adrenaline from adrenals its going to bins all to the adrenal receptors by the signal transduction pathway

Neural Stimuli

Nerve fibers stimulate hormone release Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines Outer layer is the adrenal cortex while the inner layer is the medulla. When stimulated by preganglionic sympathetic fibers from T8-L1, they secrete large quantities of the excitatory hormones norepinephrine and epinephrine (adrenaline) into nearby capillaries. When these two hormones are released in the blood they amplify all of this fight or flight stuff to give you more energy.

Nervous System Modulation

Nervous system can make adjustments to hormone levels when needed -Can modify stimulation or inhibition of endocrine glands Nervous system can override normal endocrine controls -Example: under severe stress, hypothalamus and sympathetic nervous system override insulin to allow blood glucose levels to increase Prepare body for "fight or flight"

Oxytocin

Oxytocin - (oxy=rapid & tocia=childbirth) Strong stimulant of uterine contractions released during childbirth and in nursing women -The number of receptor in the uterus peak in 3rd trimester -Stretching of the uterus and cervix signals the hypothalamus to produce -Uses PIP2-calcium second messenger system Releases Ca2+ that allows stronger contractions *positive feed back mechanism*

Oxytocin Post birth

Oxytocin - (oxy=rapid & tocia=childbirth) Strong stimulant of uterine contractions released during childbirth and in nursing women -only during suckling mechanism-ejection NOT production (thats prolactin) Acts as hormonal trigger for milk ejection during lactation

Posterior Pituitary

Pituitary secretes at least eight major hormones It has two major lobes: Posterior pituitary: composed of neural tissue that secretes neurohormones generated in the hypothalamus It is a hormone storage area and NOT a true endocrine gland Posterior lobe, along with infundibulum make up the neurohypophysis *JUST A STORAGE PLACE*

Posterior Pituitary and Hypothalamic Hormones

Posterior pituitary consists of axon terminals of neurons from hypothalamus: 1. Paraventricular neurons from the paraventricular nuclei produce oxytocin 2. Supraoptic neurons from the supraoptic nuclei produce antidiuretic hormone (ADH-antidiuretic hormones) -The axon terminals release these hormones in response to neural stimuli from the hypothalamus -Oxytocin and ADH Each composed of nine amino acids Almost identical but differ in two amino acids ^different shape binds to different receptors and has different physiological response ADH=vasopressin

Calmodulin (CaM)

Small Ca2+-binding protein that modifies the activity of many target proteins in response to changes in Ca2+ concentration.

Hormone Chemical Structure

Steroid hormone molecules are very similar in structure to cholesterol, particularly in that they have a four-ring steroid nucleus at their core. Cholesterol is the precursor molecule from which the steroid hormones are all derived -can chemically modify (same ring structure) Protein hormone molecules are made of: long folded strands of amino acids smaller strands of amino acids from a single amino acid

T3 (triiodothyronine)

T3 (triiodothyronine): form that has two tyrosines with three bound iodine atoms T4 is converted to the active T3 by 5' iodinase T3 is more biologically active than T4 within cells Both are iodine-containing amine hormones T4 and T3 are produced by the follicular cells of the thyroid gland They are regulated by TSH. The effects of T4 in vivo are mediated via T3 T4 is converted to T3 in target tissues.

T4 (thyroxine)

T4 (thyroxine): major form that consists of two tyrosine molecules with four bound iodine atoms Secreted by the thyroid follicles

Anterior Pituitary Hormones - TSH

TRH increases the secretion of TSH TSH stimulates the synthesis and secretion of trioiodothyronine (T3) and thyroxine (T4) by the thyroid gland T3 and T4 inhibit the secretion of TSH both directly and indirectly by suppressing the release of TRH effects Basal Metabolic, carbohydrate metabolism

Target Cell Specificity

Target cell activation depends on three factors: 1. Blood levels of hormone 2. Relative number of receptors on/in target cell 3. Affinity (strength) of binding between receptor and hormone ie: how well the hormones fit/interact with their receptors -High affinity receptors produce a pronounced effect and low affinity receptors decreases the cell response (ie: T3 has higher affinity for receptor than T4)

Target Cell

Target cells must have specific receptors to which hormone binds -Adrenocorticotropic (ACTH) receptors are found only on certain cells of adrenal cortex, but thyroxin receptors are found on nearly all cells of body -ACTH travels to the adrenal glands via the bloodstream. Cortisol from the adrenal then feeds back to the hypothalamus to shutdown the cycle. - only will travel and bind to the cell with those specific receptors

pituitary gland

The endocrine system's most influential gland. Under the influence of the hypothalamus, the pituitary regulates growth and controls other endocrine glands.

Growth hormone-releasing hormone (GHRH)

The secretion of GH is regulated by hypothalamic hormones on somatotropic cells Growth hormone-releasing hormone (GHRH) - stimulates GH release GHRH is produced in the hypothalamus and stimulates the GHRH receptor 1. G-protein-coupled receptor that binds GHRH 2. The GHRHR activates a Gs protein that causes a cascade of cAMP via Adenylate cyclase and release of GH 3. Triggered by low blood GH or glucose, or high amino acid levels Growth hormone-inhibiting hormone (GHIH) or (somatostatin) inhibits release

Endocrinology

The study of hormones and endocrine organs

sympathetic nervous system

The sympathetic division mobilizes the body during extreme situations such as exercise, excitement and emergencies. -"fight or flight mechanism" Colloquially known as "fight or flight." Neural stimuli The Sympathetic Division (T1 - L2-thoracic and lumbar) is responsible for Pupil dilation, Inhibit tear, nasal mucus, saliva production, Skin blood vessel constriction (shunt blood away from skin and to vital organs), Sweat, Increase heartrate and blood flow to heart muscle, Bronchodilation, Liver/gallbladder - release glucose, all having to do with fight or flight

Synthesis of TH

Thyroid gland stores hormone extracellularly in follicle lumen until triggered by TSH to release Seven steps involved in synthesis of TH: 1. Thyroglobulin is synthesized and discharged into follicle lumen 2. Iodide is trapped: iodide ions (I-) are actively taken into cell and released into lumen 3. Iodide oxidized: electrons are removed, converting it to iodine (I2) 4. Iodine is attached to tyrosine: mediated by peroxidase enzymes -Monoiodotyrosine (MIT): formed if only one iodine attaches -Diiodotyrosine (DIT): formed if two iodines attach 5. Iodinated tyrosines link together to form T3 and T4 -If one MIT and one DIT link, T3 is formed -If two DITs link, T4 is formed 6. Colloid is endocytosed by follicular cells -Vesicle is then combined with a lysosome 7. Lysosomal enzymes cleave T3 and T4 from thyroglobulin -Hormones are secreted into bloodstream -Mostly T4 secreted, but T3 is also secreted -T4 must be converted to T3 at tissue level

TRH and reproductive hormone

Thyrotropin-releasing hormone (TRH) has a stimulatory effect on prolactin release Hypersecretion of prolactin is more common than hyposecretion Hyposecretion not a problem in anyone except women who choose to nurse Hyperprolactinemia is the most frequent abnormality of anterior pituitary tumors Clinical signs include inappropriate lactation, lack of menses, infertility in females, and impotence in males *don't see prolactin going back and shutting off original (feedback loop) *be cognizant of the scenario with prolactin questions

When sugars cannot be used as fuel...

When sugars cannot be used as fuel, as in DM, fats are used, causing lipidemia: high levels of fatty acids in blood -Fatty acid metabolism results in formation of ketones (ketone bodies) Ketones are acidic, and their build-up in blood can cause ketoacidosis Also causes ketonuria: ketone bodies in urine Untreated ketoacidosis causes hyperpnea, disrupted heart activity and O2 transport, and severe depression of nervous system that can possibly lead to coma and death *go from sugars to fats to proteins*

GH and Bone Growth

Within the epiphyseal growth plate -GH stimulatres chondrocytes to synthesize and respond to IGF-I IGF-I produced locally (along with IGFI produced by the liver) stimulates cell division

adrenal glands

a pair of endocrine glands that sit just above the kidneys and secrete hormones (epinephrine and norepinephrine) that help arouse the body in times of stress.

Thyroxine-binding globulins (TBGs)

along transthyretin and serum albumin transport T4 and T3 in the bloodstream TBG is synthesized primarily in the liver and has the highest affinity for T4 and T3

kinase

an enzyme that catalyzes the transfer of a phosphate group from ATP to a specified molecule. kinAses add; phosphoTases take

Hormones

chemical messengers secreted by cells into the extracellular fluids (ECF) -Need to bind to the target cell receptor (protein on the cell membrane- external or internal cell membrane) and the ligand *When compared to the nervous system hormonal responses are typically slower but longer lasting* like texting from one organ system to another

phosphodiesterase

enzyme that degrades cAMP, producing AMP, to terminate signaling

Positive feedback loop

feedback loop that causes a system to change further in the same direction

Hypoparathyroidism

following gland trauma or removal can cause hypocalcemia -remove thyroid also remove the parathyroid *now no levels of calcium Causes neurons to become more excitable Results in muscle twitches (tetany), respiratory paralysis, and death

Pancreas

found behind the stomach in the abdomen that has two glands (exocrine and endocrine) combined in the same organ The exocrine function is performed by the acinar cells produce enzymes that travel via ducts to the duodenum during digestion The endocrine function component in performed by small clusters of cells or pancreatic islets commonly referred to as the islets of Langerhans. -Alpha (α) cells produce glucagon (hyperglycemic hormone) -Beta (β) cells produce insulin (hypoglycemic hormone)

Hormonal Stimuli is also regulated by sugar

high levels of sugar=pancreaus has alpha cells that release glucagon; beta cells release insulin Glycogen is stored in the liver -muscles also release sugar

Chemical messengers of Endocrine system

hormones, autocrines, paracrines Hormones: long-distance chemical signals; travel in blood or lymph ^Endocrine-over great distances- very far down gland to get to receptor site (like going to another state) Autocrines: chemicals that exert effects on same cells that secrete them (self signaling) -travels to a signal on itself Paracrines: locally acting chemicals that affect cells other than those that secrete them (across from itself) -short distance to neighboring site *Autocrines and paracrines are local chemical messengers that do not travel great distances and not considered part of endocrine system*

Hyposecretion of TH

in adults can lead to myxedema -Symptoms include low metabolic rate, thick and/or dry skin, puffy eyes, feeling chilled, constipation, edema, mental sluggishness, lethargy -Results in mucopolysaccharides being deposited in the dermis, which causes swelling area. If due to lack of iodine, a goiter may develop Follicular cells produce colloid but can not iodinate it. The pituitary increases TSH to produce TH but only causes the thyroid to synthesize more and more unusable thyroglobulin Thyroid enlarges Iodized Salt provides dietary supply

Wolff Chaikoff Effect

inhibits the formation of thyroid hormones inside the thyroid follicle and the release of thyroid hormones into the bloodstream Here the sodium-iodide symporter transports the excess iodine into the thyroid This causes partial inhibition of thyroid peroxidase (TPO) and a decrease in thyroid hormone synthesis. -low-moderate levels iodide-> hypo -no levels-> no T3 or T4 -High levels-> kicks on TPO and that shuts off the synthesis ^inverse correlation

Adrenocorticotropic hormone (ACTH) or corticotropin

it is secreted by corticotropic cells in the anterior pituitary Precursor to ATCH is pro-opiomelanocortin ^pro meaning in an off status -> to become active the protein must be cleaved or cut (rep by dashed lines) ^ providing cell with stockpile to be turned on after the break or cleave ACTH stimulates adrenal cortex to release corticosteroids and is produced in response to biological stress -It functions to release cortisol from the cortex of the adrenal gland Cortisol - a glucocorticoid hormone that can -Increase blood sugar -Suppress the immune system -Decrease bone formation -Increase the metabolism of fat, protein, and carbohydrates -It is also expressed in diurnal cycles where levels peak in the early morning and reach the lowest level 3 to 5 hours after the onset of sleep

Hyposecretion in infants

leads to cretinism -Symptoms include intellectual disabilities, short and disproportionately sized body, thick tongue and neck -Genetic deficiency of fetal gland -TH replacement therapy can be used if diagnosed early enough

how do they do the TH replacement therapy?

levothyroxine

Paracrines

locally acting chemicals that affect cells other than those that secrete them Islet of Langerhons/ Pancreatic Islet ^Groups of cells around the blood vessles 3 Types Alpha-Secretes glucagon Beta-Secretes insulin ^if doesn't work-Type 1 Diabetes Delta: secrete somatostatin (helps with carb metabolism, inhibits other two hormones

Hypersecretion of TH

most common type is Graves' disease -Autoimmune disease: body makes abnormal antibodies directed against thyroid follicular cells -Antibodies mimic TSH, stimulating TH release ^rather than have regulatory process release TSH and then TSH release T3, and T4, the receptors get confused and release massive amounts of T3 and T4 mimicking TSH *Nothing is stopping it!!! -Symptoms include elevated metabolic rate, sweating, rapid and irregular heartbeats, nervousness, and weight loss despite adequate food -Exophthalmos may result: eyes protrude as tissue behind eyes becomes edematous (build up of fluid) and fibrous -Treatments include surgical removal of thyroid or radioactive iodine to destroy active thyroid cells ^radioactive iodide, like chemo, will locate and accumulate bad thyroid cells and kills them

Gonads

ovaries and testes

tropic hormones (tropins)

regulate secretion of other hormones in different endocrine glands diagram

Parathyroid glands

small pea-like organs that regulate calcium and phosphate balance in blood, bones, and other tissues

How do the cells on the anterior pituitary know when to release the hormones?

the inhibitory hormone enters the secondary plexus when levels start to build up and enter the cells when need to shut off the thyroid stimulating hormone -if levels are low then it turns back on again to circulate hormone activation

Pancreus

the organ that lies behind the stomach and that makes digestive enzymes and hormones that regulates sugar levels -both endocrine (hormones) and exocrine (digestion)

T3 and T4

thyroid hormones responsible for our metabolic rate, synthesis of protein, breakdown of fats, use of glucose for ATP production