A&P II Chapter 16

3 different types of chemical signals

(1) Endocrine (2) paracrine (3) autocrine.

Adrenal glands

Adrenal glands - located on superior aspect of each kidney; roughly pyramid-shaped; produce catecholamine and steroid hormones. Divided into two distinct regions: an outer adrenal cortex surrounding an inner adrenal medulla. Cortex is further subdivided into three distinct zones, each of which produces steroid hormones derived from cholesterol. Outer zona glomerulosa - consists of densely packed cells that produce mineralocorticoid hormones. Middle zona fasciculata - consists of cells stacked on one another in columns; secrete glucocorticoids and androgenic steroids. Inner zona reticularis - thin layer of cells arranged loosely in clusters; secrete glucocorticoids and androgenic steroids.

Hormones of hypothalamus, anterior pituitary, and their target tissues are maintained at normal levels by negative feedback loops with multiple levels (tiers) of control (Figure 16.8)

Allow endocrine system to tightly regulate conditions within body. Critical for maintaining homeostasis.

Two basic types of hormones are classified based on chemical structure

Amino-acid hormones - consist of one or more amino acids ranging in size from solitary amino acids (amine hormones) to multiple amino acids (peptide hormones), and even complete proteins (protein hormones); generally hydrophilic, binding to plasma membrane receptors. Steroid hormones - derived from cholesterol; hydrophobic hormones that bind to receptors in cytosol or nucleus.

Primary endocrine organs

Anterior pituitary gland - in sphenoid bone of skull. Thyroid gland - in anterior neck. Parathyroid gland - on posterior side of thyroid gland. Adrenal cortices - on superior side of each kidney. Endocrine pancreas - in left side of abdominal cavity mostly posterior to stomach. Thymus - in superior mediastinum.

Thyroid disorders

Cause serious imbalances due to systemic effects of thyroid hormones; overproduction leads to hyperthyroidism while underproduction leads to hypothyroidism; common disorders include (Figure 16.15). Hyperthyroidism - characterized by weight loss, heat intolerance, disruptions in blood pressure and heart rhythms, and development of a goiter and exophthalmos (enlargement of thyroid gland and protruding eyeballs, respectively). Graves' disease - most common cause of hyperthyroidism; results from immune system producing abnormal proteins that mimic actions of TSH on thyroid gland. Hypothyroidism - characterized by weight gain, cold intolerance, slow heart rate, low blood pressure, and a goiter; can be due to an immune system disorder or a lack of available iodine. Congenital hypothyroidism (cretinism) - develops when an infant is born with inadequate thyroid function; can lead to delayed physical and nervous system development; potentially mental retardation if left untreated.

Nervous system compared to Endocrine system II

Cells of endocrine system are generally not in close direct contact with target cells; instead, hormones are secreted into bloodstream where they travel to interact with target cells. Hormones can elicit an effect in a matter of seconds or it could take hours or days. Once begun, a hormone's effect is generally longer-lasting than that of nervous system.

Paracrine chemical signals

Chemicals are secreted by cells into extracellular space to affect nearby but different types of cells

Autocrine chemical signals

Chemicals are secreted by cells into interstitial fluid; elicits effects from same cell or cell type

Calcium ion homeostasis

Chief cells secrete parathyroid hormone and thyroid secretes calcitonin, both of which have opposing effects on calcium ion concentration in blood; keeps this vital ion within a normal range (Figure 16.16; Table 16.2).

Hormones misc

Circulate in bloodstream until they are taken up by a target cell or broken down and deactivated. Amount of a particular hormone in blood at a given moment depends on how fast and how much hormone an endocrine gland has produced and how fast secreted hormone is removed from blood.

Each tier includes a stimulus, receptor, control center, and response/effector (Figure 16.8):

First tier - neuroendocrine cells of hypothalamus secrete releasing and inhibiting hormones in response to change in homeostatic variable (tropic hormones - control center hormones). Second tier - involves hypothalamus tropic hormones' effect on anterior pituitary; stimulates or inhibits anterior pituitary hormone secretion. Third tier - involves actions of anterior pituitary hormones at target tissues; target tissue glands secrete hormones that can affect various homeostatic variables. Once homeostatic variable that stimulated activity at hypothalamus returns to a normal set point, change is detected at hypothalamus and it stops secreting tropic hormones. Anterior pituitary changes its hormone secretion accordingly; target tissues follow suit and feedback loop is closed.

T3 and T4 production is regulated by a negative feedback loop with following tiers of control

First tier involves thyrotropin-releasing hormone (TRH) from hypothalamus and second thyroid-stimulating hormone (TSH) from anterior pituitary gland. TSH stimulates production of T3 and T4 by follicle cells, secretion of T3 and T4 from follicle cells into blood, and growth and development of thyroid gland. Production and secretion of TRH and TSH increases when levels of free T3 and T4 fall or when body is exposed to cold temperatures. Secretion of TRH and TSH is inhibited by rising levels of free T3 and T4; TSH is also inhibited by somatostatin.

Oxytocin - produced by hypothalamus and stored in axon terminals of posterior pituitary gland

Functions of oxytocin are primarily focused on reproduction; target cells are in mammary glands of breast tissue and smooth muscle of uterus. In nursing mother, suckling stimulates oxytocin release; causes mammary glands to contract resulting in milk ejection.

Growth hormone disorders: imbalances in GH secretion can result in various disruptions in growth

Gigantism - hypersecretion of GH before epiphyseal plates have closed; leads to extremely tall individuals; excess GH also increases size of other tissues such as heart. Acromegaly - hypersecretion of GH after epiphyseal plate closure; most affected are tissues of head, face, hands, and feet, as well as liver and heart; progressively distorts these various organs; can lead to heart failure. Pituitary dwarfism - a condition of GH hyposecretion; leads to individuals that are short in stature but with otherwise proportional limbs and trunk.

Effects of Cortisol

Glucocorticoids produced in zona fasciculata and zona reticularis; main role is to help mediate body's response to stress; cortisol (hydrocortisone) is most potent glucocorticoid. Stress response (series of events that maintains homeostasis when body is faced with a stressor); involves regulation of blood glucose levels and following responses. Cortisol stimulates liver cells to synthesize enzymes involved in gluconeogenesis (production of new glucose molecules from amino acids and fatty acids); increases blood glucose levels. Cortisol induces breakdown of proteins in skeletal muscle; releases free amino acids into blood that can be converted to glucose by gluconeogenesis. Cortisol acts on adipocytes to release fatty acids into blood; can be converted into fuel or glucose by gluconeogenesis in liver. Cortisol receptors are found in cells throughout body such that actions of this steroid hormone are widespread; hormone is a potent anti-inflammatory that decreases levels of certain leukocytes.

Endocrine glands

Group of organs found throughout body; all regulate other cell types by producing and secreting hormones. Ductless glandular epithelial cells secrete hormones into extracellular fluid for transport by bloodstream. This system consists of two groups of organs (1) Primary organs have only endocrine functions (2) Secondary organs have both endocrine and a variety of non-endocrine functions.

Growth hormone

Growth hormone (GH; somatotropin) - produced and secreted by somatotrophs; release GH periodically throughout day, with peak secretion occurring during sleep. Main function of GH is to regulate growth of various target tissues including skeletal and cardiac muscle, adipose, liver, cartilage and bone; can be either short or long-term effects (Figure 16.9, 16.10). Short-term effects - generally metabolic; include promotion of fat breakdown, generation of new glucose in liver, and inhibition of glucose uptake by muscle fibers, all of which increase blood glucose and fatty acid levels; can be used by cells for fuel and raw materials for growth (Figure 16.9a). Long-term effects are not all directly mediated by GH: GH acts on the liver and other target tissues to promote production of hormone insulin-like growth factor (IGF) (Figure 16.9b). Affects nearly every cell in body; triggers rapid protein synthesis and cell division leading to increased longitudinal bone growth and muscle development in children. Decreases blood glucose ("insulin-like") concentration in blood by stimulating glucose uptake by cells; in opposition to initial actions of GH. GH + IGF continue to play important roles in adults, such as promoting muscle development as well as regulation of body mass

The regulation of growth hormone (GH) release.

Growth hormone is regulated by two hypothalamic hormones: Growth hormone-releasing hormone (GHRH) and somatostatin (Figure 16.10). Growth hormone-releasing hormone (GHRH) stimulates release of GH; secretion increases during exercise, fasting, and stress, and after ingestion of a protein-rich meal. GH release, like that of TSH, is inhibited by hypothalamic hormone somatostatin.

Secondary endocrine organs

Heart, kidneys, and small intestines to testes and ovaries. Neuroendocrine organs: Include hypothalamus and pineal gland in brain and adrenal medulla in core of adrenal gland. Each consists of nervous tissue but secretes chemicals that act as hormones (neurohormones).

Regulation of hormone secretion - Secretion can be initiated or inhibited by several different stimuli

Hormonal stimuli - some endocrine cells increase or decrease their secretion in response to secretion of other hormones. Humoral stimuli - many endocrine cells respond to concentration of a certain ion or molecule in blood or extracellular fluid. Neural stimuli - some endocrine cells respond to signals from nervous system.

Hormone target cells and receptors

Hormones are able to affect only particular cells called target cells; contain specific protein receptors to which hormones bind. Three-dimensional shapes are highly specific for hormone molecule that they bind; can bind when hormone concentration is extremely low; example of Structure-Function Core Principle. Can be either embedded in plasma membrane or reside within cytosol or nucleus of a target cell

Hormone receptor location

Hydrophilic hormones (dissolve) cannot readily cross plasma membrane so generally interact with receptors found embedded in target cell's plasma membrane. Hydrophobic hormones are able to cross through plasma membrane so generally interact with receptors found in cytosol or nucleus.

Aldosterone disorders:

Hypersecretion of aldosterone (hyperaldosteronism) can lead to hypokalemia (low blood potassium ion level), hypernatremia (high blood sodium ion level), and hypertension (high blood pressure)

Adrenal insufficiency

Hyposecretion of both cortisol and aldosterone are characteristic of Addison's disease; render individual susceptible to adrenal crisis. Adrenal crisis results in fluid, electrolyte, and acid-base homeostasis disruptions. Many causes, including abnormal development of adrenal gland, deficiency in certain enzymes required to produce steroid hormones, and destruction of adrenal glands by individual's immune system.

Regulation of calcium ion homeostasis

Involves a negative feedback loop that maintains calcium ions with a normal range (Figure 16.16): Stimulus - blood calcium ion level decreases below range Receptor - chief cells in parathyroid gland detect a low blood calcium ion level. Control center - chief cells increase PTH secretion. Effector/response: Effects of PTH on target cells increase blood calcium ion concentration Blood calcium ion level returns to normal range; negative feedback to chief cells decreases PTH secretion

Functional relationships between the hypothalamus and pituitary gland

Hypothalamic-hypophyseal portal system -specialized blood supply; allows both hypothalamus and pituitary to deliver their hormones directly to their target cells. Tiny capillaries merge in hypothalamus to form larger portal veins that travel through infundibulum. Portal veins lead to a second group of capillaries in anterior pituitary gland. Systems like this, in which capillaries are drained by veins that lead to another set of capillaries, are called portal systems. No hormones are actually made in posterior pituitary; two neurohormones are produced by hypothalamus then stored and released from posterior pituitary (Figure 16.7a): Antidiuretic hormone (ADH) Oxytocin

Functional Relationship of Hypothalamus and Anterior Pituitary. Hypothalamus controls many functions of anterior pituitary

Hypothalamus produces and releases tropic hormones that either stimulate (releasing hormones), or inhibit (inhibiting hormones) release of hormones from anterior pituitary (Figure 16.7b). Tropic hormones travel from hypothalamus to anterior pituitary via hypothalamic-hypophyseal portal system. Many anterior pituitary hormones are also tropic; control secretion of hormones by various endocrine glands in body.

Hypothalamus and the Pituitary Gland

Hypothalamus: Vital to many homeostatic processes including regulation of thirst, hunger, fluid balance, body temperature, sleep/wake cycle, and certain reproductive functions. Anatomical and functional relationship between hypothalamus and pituitary gland is important to homeostatic regulation. Several hypothalamic nuclei and anterior pituitary hormones directly control certain body functions; others are tropic hormones (control secretion of hormones from other endocrine glands). Not to be confused with trophic hormones (induce growth in target cells); note that some hormones have both tropic and trophic effects on target cells. Some hypothalamic functions are performed directly by neurons that terminate in posterior pituitary whereas other hormones target anterior pituitary.

Hormones

Interact with specific target cells and influence their functions in order to maintain fluid, electrolyte, and acid-base homeostasis, promote growth, and regulate metabolic reactions.

Cortisol disorders

Involve either oversecretion of cortisol or long-term administration of corticosteroids (Figure 16.20): Cushing's disease - oversecretion from adrenal cortex, usually from a tumor. Iatrogenic Cushing's syndrome - disorder caused by long-term administration of glucocorticoid-containing products. Lipolysis releases fatty acids from upper and lower limbs, which become slim; deposited in adipose tissue in characteristic places: Trunk, Face (causing a round face called moon facies) Back of neck (producing a "buffalo hump") Breakdown of protein in muscles leads to muscle wasting; released fats and amino acids are converted into glucose, causing hyperglycemia. Slight mineralcorticoid effect causes hypertension; effect on leukocytes causes immunosuppression; effect on osteoblast activity and calcium absorption may cause osteoporosis.

Parathyroid hormone (PTH)

Major factor in maintenance of blood calcium ion concentration; secreted in response to declining calcium ion levels in blood; triggers following effects: Increases release of calcium ions from bone by stimulating osteoclast activity. Increases absorption of dietary calcium ions by small intestine. Acts on kidneys to convert inactive vitamin D into its active form, calcitriol; increases absorption of dietary calcium ions from small intestine. Increases reabsorption of calcium ions from fluid in kidneys.

Multiple factors regulate aldosterone synthesis and secretion:

Major factors increase aldosterone release: elevated blood potassium ion concentration, a decrease in blood pH, and a hormone called angiotensin-II. In HPA axis, corticosteroid-releasing hormone (CRH) from hypothalamus stimulates release of ACTH from anterior pituitary, which then stimulates production and release of aldosterone.

Hormone interactions - maintenance of homeostasis requires multiple hormones

Many hormones have complementary actions; each hormone interacts with a different target cell in order to accomplish a common goal. Some hormones (synergists) can act on same target cell to exert same effect; effect is more pronounced with interaction of multiple hormones than any one individual hormone by itself. Some hormones called antagonists act on same cells but have opposite effects.

Nervous system compared to Endocrine system I

Operates through a series of neurons that directly affect their target cells through release of neurotransmitters; effects are almost immediate but are short-lived unless stimulation is repetitive.

Endocrine system

Organs of this complex system work by synthesizing and secreting chemical messengers called hormones.

Calcitonin

Produced and secreted by parafollicular cells; released when calcium ion level in blood increases above normal: Primary target is osteoclast cells in bone; osteoclast activity is inhibited by presence of calcitonin; allows osteoblast activity. Unopposed osteoblast activity reduces blood calcium ion levels as these ions are incorporated into bone matrix Table 16.2 summarizes hormones of thyroid and parathyroid glands.

Antidiuretic hormone (ADH): Water retention, also known as vasopressin, controls water balance

Produced continually in low amounts by hypothalamic neurons; transported through axons in infundibulum to axon terminals in posterior pituitary; stored in synaptic vesicles. Axon terminals do not have synapses; instead release ADH into blood vessels when stimulated by action potentials. ADH allows for insertion of water channels (aquaporins) into plasma membranes of cells that make up kidney tubules. Water passes into cytosol of these cells, then back into extracellular fluid and finally to blood; would otherwise have been eliminated from body in urine. Diabetes insipidus - disease caused by lack of ADH secretion or activity; causes extreme thirst and signs of dehydration because body is unable to conserve most water consumed.

Hormones of Adrenal Cortex

Production of steroid hormones from three zones of cortex is partially regulated by a multi-tiered negative feedback loop called hypothalamic-pituitary-adrenocortical (HPA) axis (Figures 16.18-16.20). Aldosterone, main mineralocorticoid, regulates concentration of certain minerals (sodium and potassium ions) in body. Maintains concentrations of extracellular sodium and potassium ions within their normal ranges; gradients of sodium and potassium ions across plasma membranes are critical to functioning of muscle cells and neurons. Regulates extracellular fluid volume; effects on sodium and chloride ions in kidney tubule cells create a concentration gradient that favors movement of water by osmosis from fluid in those tubules to extracellular fluid and blood; example of Gradients Core Principle. Maintains blood pressure with other organs through a complex series of interactions called renin-angiotensin-aldosterone system (RAAS); functions to increase blood pressure and to preserve blood flow to heart, brain, and kidneys. Maintains acid-base homeostasis; activates hydrogen ion pumps in certain cells of kidney tubules; pumps transport hydrogen ions from extracellular fluid into fluid of tubules; excreted in urine, lowering hydrogen ion concentration (pH) of blood, preserving slightly alkaline pH.

Effects of thyroid hormone. Almost every cell in body contains thyroid hormone receptors; makes their effects widespread; three main categories of effects are as follows

Regulation of metabolic rate and thermoregulation - thyroid hormones set basal metabolic rate (amount of energy required by body at rest) by increasing rate of ATP consumption, increasing gluconeogenesis, and by initiating energy-requiring reactions in these same target cells; heat is generated, which is critical for core body temperature homeostasis. Promotion of growth and development - thyroid hormones are required for normal bone growth, muscle growth, and nervous system development Synergism with sympathetic nervous system -increases in thyroid hormone levels act on target cells of sympathetic nervous system and increase (up-regulate) receptors for sympathetic neurotransmitters; affects regulation of blood pressure, heart rate, and other sympathetic activities.

Pituitary gland

Small organ that sits in sella turcica of sphenoid bone; composed of following two structurally and functionally distinct components. Anterior pituitary (adenohypophysis) - true gland composed of hormone-secreting glandular epithelium ("adeno") Posterior pituitary (neurohypophysis) - made up of nervous tissue ("neuro")

Effects of hormone actions

Stimulating secretion from an endocrine or exocrine cell. Activating or inhibiting enzymes. Stimulating or inhibiting mitosis and/or meiosis. Opening or closing ion channels in cell's plasma membrane and/or altering its membrane potential. Activating or inhibiting transcription of genes that code for RNA or proteins (gene expression).

Maintaining homeostasis: regulation of hormone secretion by negative feedback loops.

Stimulus - a regulated physiological variable deviates from its normal range. Receptor - receptors on target cells detect deviation of variable. Control center - stimulated control center (often endocrine cell) increases or decreases its secretion of a particular hormone. Effector/response - hormone triggers a response in its target cells that moves conditions toward normal range. Homeostatic range - As variable returns to its normal range, feedback to control center decreases response.

Sequence of events leading to thyroid hormone synthesis (Figure 16.13)

Thyroglobulin - large thyroid hormone precursor protein; secreted by follicle cells into colloid. Iodide ions are secreted into colloid; converted to iodine atoms that attach to thyroglobulin. Iodinated thyroglobulin enters follicle cell by endocytosis and is converted to T4 and T3 by lysosomal enzymes. T4 and T3 are finally released into bloodstream. Many target tissues can convert T4 to more active T3; T4 lasts longer in blood than T3 so acts as a reservoir for potential T3.

Anatomical features of thyroid and parathyroid glands

Thyroid gland - secretes thyroid hormone and calcitonin Located anterior neck, just superficial to larynx. Butterfly-shaped gland consists of right and left lobes connected by isthmus (small band of thyroid tissue). Microscopically, gland is composed of multiple spheres called thyroid follicles; follicle cells found at outer edge of follicles produce and secrete thyroid hormones. Colloid - protein-rich, gelatinous material that contains precursor for thyroid hormone and high concentration of iodine atoms; both important to thyroid hormone synthesis. Parafollicular cells - in spaces between adjacent thyroid follicles; large cells that produce hormone calcitonin.

Chemical structure of thyroid hormone

Thyroid hormone consists of an amino acid core bound to either 3 (triiodothyroxine, T3) or 4 (thyroxine, T4) iodine atoms. Both T3 and T4 are physiologically active but T3 much greater so; T4 is commonly converted to T3 in some target tissues. T3 and T4 are both amino acid-based hormones although they are an exception in that they are more hydrophobic than other amino acid-based hormones; do not interact with plasma membrane-bound receptors. Both T3 and T4 enter target cell nucleus where they bind with receptors that either activate or inhibit specific gene transcription.

Anterior pituitary hormones that affect other glands: Tropic hormones (control secretion of hormones from other endocrine glands) by anterior pituitary include

Thyroid-stimulating hormone (TSH, thyrotropin) - stimulates development of thyroid gland and its secretions, (thyroid hormones); TSH release is stimulated by hypothalamic hormone thyrotropin-releasing hormone (TRH). Adrenocorticotropic hormone (ACTH, corticotropin) - stimulates development of adrenal gland and synthesis of various steroid hormones; ACTH release is stimulated by hypothalamic hormone corticotropin-releasing hormone (CRH). Prolactin (PRL) - stimulates growth of mammary gland tissue, initiates milk production after childbirth, and maintains milk production for duration of breastfeeding; PRL release is stimulated by hypothalamic hormone prolactin-releasing hormone; inhibited by prolactin-inhibiting factor (known to be dopamine). Luteinizing hormone (LH; gonadotropin) Male - stimulates production of hormone testosterone by testes under direction of hypothalamic hormone gonadotropin-releasing hormone (GnRH) Female - stimulates production of estrogen and progesterone from ovaries; triggers release of an oocyte in process of ovulation; also under direction of GnRH.

Number of receptors a target cell displays

Up-regulation - process by which target cells produce and display a greater number of receptors in response to a temporary increase in hormone level in blood. Down-regulation - process by which target cells decrease number of receptors displayed in response to prolonged exposure to a high level of hormone in blood

Understanding Relationship between Negative Feedback Loops and Thyroid Function

When T3 and T4 levels in blood drop, receptors in cells of hypothalamus detect change and secrete more TRH; stimulates anterior pituitary to secrete more TSH. Under normal conditions, elevated TSH will stimulate thyroid gland to produce more T3 and T4; when T3 and T4 levels increase, receptors in both hypothalamus and anterior pituitary gland detect this change, and TRH and TSH levels decrease through negative feedback. However, in hypothyroidism, thyroid gland is unable to produce more T3 and T4; hypothalamus and anterior pituitary don't "know" that thyroid gland is not functioning; all their receptors sense is that T3 and T4 levels are low, so cells continue to secrete more TRH and TSH in an attempt to stimulate thyroid. This leads to characteristic elevated TSH and decreased T3 and T4 levels seen with hypothyroidism.This situation works in reverse with hyperthyroidism; under normal conditions, cells of hypothalamus and anterior pituitary gland decrease production of TRH and TSH when levels of T3 and T4 rise. In case of hyperthyroidism, levels of T3 and T4 are extremely elevated; detected by receptors of hypothalamus; for this reason, production and secretion of TRH and TSH fall to nearly zero. This leads to characteristic decreased TSH with elevated T3 and T4 levels seen in hyperthyroidism.