FINAL
Describe the regulation of calcitonin release and the cell of origin and target organs for calcitonin action.
Calcitonin is a 32 amino acid peptide hormone derived from procalcitonin, produced by cells of neural crest origin (parafollicular or C cells) in the thyroid gland. Release of calcitonin is regulated by plasma calcium levels through a Ca2 + receptor on the parafollicular cells. Elevations in plasma calcium higher than 9 mg / dL stimulate the release of calcitonin. Calcitonin has a half-life of approximately 5 minutes and is metabolized and cleared by the kidney and the liver. Main physiologic functions to decrease plasma calcium and phosphate concentrations. 2 Target organs bone and kidney: Decreases bone resorption inhibition of osteoclast motility, differentiation, and ruffled border formation. Kidney: increases urinary calcium excretion by inhibition of renal tubular calcium reabsorption.
Identify the consequences of oversecretion and undersecretion of glucocorticoids and mineralocorticoids.
Cushing's syndrome is caused by too high a level of glucocorticoid in the body. This can be caused by taking steroid medication long-term (the common cause) or by the body making too much cortisol (the main glucocorticoid made by the body). Insufficient production of cortisol, often accompanied by an aldosterone deficiency, is called hypoadrenocorticism or Addison's disease. Most commonly, this disease is a result of infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortex. As with Cushing's disease, numerous and diverse clincial signs accompany Addison's disease, including cardiovascular disease, lethargy, diarrhea, and weakness. Aldosterone deficiency can be acutely life threatening due to disorders of electrolyte balance and cardiac function. Hyperaldosteronism is a disease in which the adrenal gland(s) make too much aldosterone which leads to hypertension (high blood pressure) and low blood potassium levels. Primary hyperaldosteronism can be caused by either hyperactivity in one adrenal gland (unilateral disease) or both (bilateral disease). Hypoaldosteronism is a condition characterized by the shortage (deficiency) or impaired function of a hormone called aldosterone. The symptoms of this condition include low sodium (hyponatremia), too much potassium (hyperkalemia), and a condition where the body produces too much acid (metabolic acidosis).
Describe the physiologic functions of the principal components of the male reproductive system.
Epididymis - H+ secretion, decrease the pH of luminal fluid Seminal vesicle - secretion and storage of fructose rich product, prostaglandins, ascorbic acid, fibrinogen and thrombin like proteins. Prostate - secretion & Storage of fluid a rich in acid phosphatase and protease. Cowper glands - mucus upon arrival sertoli cells - form blood-testis barrier, support spermatogonia, Signal spermatogenesis, produce inhibin B leydig cells - in connective tissue, produce testosterone
Understand the nutrient, neural, and hormonal mechanisms that regulate pancreatic hormone release.
Glucose is the principal stimulus for insulin release Glucose enters the beta cell via glucose transporter protein (GLUT 2) undergoes glycolysis leaving to generation of ATP The increased ATP / ADP ratio leads to inhibition and closure of the ATP sensitive potassium channels (the target of sulfonylureas drugs) resulting in plasma membrane depolarization and opening of the voltage dependent calcium channels. The increased calcium influx coupled with mobilization of calcium from intracellular stores leads to the fusion of insulin containing secretory granules with the plasma membrane and the release of insulin and c-peptide into the circulation. Glucose releases inhibited by hyperglycemia and stimulated by hypoglycemia. A meal rich in carbohydrates suppresses glucagon release and stimulates insulin release from the beta cells through intestinal release of glp-1. somatostatin also inhibits glucagon release. High amino acid levels following an amino acid Rich meal stimulate glucagon release. Epinephrine stimulates release of glucagon through a beta2-adrenergic mechanism whereas it suppresses insulin release from beta cells through alpha2-adrenergic mechanism. Vagal (parasympathetic) stimulation increases glucagon release.
Describe gonadotropin control of ovarian function.
Gonadotropin synthesis and release and differential expression are under both positive and negative feedback control by ovarian steroid and peptide hormones. Ovarian hormones can decrease gonadotropin release both by modulating gonadotropinreleasing hormone (GnRH) pulse frequency from the hypothalamus and by affecting the ability of GnRH to stimulate gonadotropin secretion from the pituitary itself Gonadotropin releasing hormone secreted by the hypothalamus controls ovarian and uterine cycle, stimulates the release of FSH and LH from anterior pituitary
Identify the principal hormones secreted from the endocrine pancreas, their cells of origin, and their chemical nature.
HORMONES: Insulin is hypoglycemic - it decreases blood glucose. Beta cells. 51 aa's. Insulin is a peptide hormone synthesized from preproinsulin. Preproinsulin post-translational modified in the ER to form proinsulin. Active insulin is produced by modification of proinsulin via cleavage of the C-peptide. Both released in response to glucose stimulation. Glucagon is hyperglycemic - it increases blood glucose. Glucagon is a 29 amino acid polypeptide hormone secreted by the alpha cells of the islets of langerhans. Glucagon is synthesized as pro-glucagon and then proteolytically processed to yield glucagon. Pancreatic somatostatin inhibits the release of both insulin and glucagon and slows the activity of the digestive tract. Somatostatin is a 14 amino acid peptide hormone produced by the Delta cells of the pancreas. Release is stimulated by high-fat, high-carbohydrate, and particularly protein-rich meals. Inhibited by insulin. Generalized inhibitory effects on virtually all gastrointestinal and pancreatic exocrine and endocrine functions. Pancreatic polypeptide regulates secretion of pancreatic digestive enzymes and inhibits release of bile by the gallbladder. Pancreatic polypeptide is a 36 amino acid peptide hormone that belongs to a peptide family including neuropeptide Y and peptide YY. It is produced in the endocrine type F cells located in the periphery of pancreatic islets and is released into the circulation after a meal, exercise, and vagal stimulation. The effects of pancreatic polypeptide include inhibition of pancreatic exocrine secretion, gallbladder contraction, modulation of gastric acid secretion, and gastrointestinal motility. Pancreatic polypeptide crosses the blood-brain barrier and has been postulated to play a role in regulating feeding Behavior.
Describe the consequences of excess or deficiency of parathyroid hormone and of vitamin D.
Hyperparathyroidism is a condition in which one or more of the parathyroid glands become overactive and secrete too much parathyroid hormone (PTH). This causes the levels of calcium in the blood to rise, a condition known as hypercalcemia. Hypercalcemia is a condition in which the calcium level in your blood is above normal. Too much calcium in your blood can weaken your bones, create kidney stones, and interfere with how your heart and brain work. Hypoparathyroidism is the state of decreased secretion or decreased activity of parathyroid hormone (PTH). This lack of PTH leads to decreased blood levels of calcium (hypocalcemia) and increased levels of blood phosphorus (hyperphosphatemia). Severe symptoms of hypocalcemia include: confusion or memory loss. muscle spasms. numbness and tingling in the hands, feet, and face. The main consequence of vitamin D toxicity is a buildup of calcium in your blood (hypercalcemia), which can cause nausea and vomiting, weakness, and frequent urination. Vitamin D toxicity might progress to bone pain and kidney problems, such as the formation of calcium stones. Vitamin D deficiency can lead to a loss of bone density, which can contribute to osteoporosis and fractures
List the principal target organs for insulin and glucagon action and their major physiologic effects.
INSULIN- target organ The primary targets for insulin are liver, skeletal muscle, and fat. Insulin has multiple actions in each of these tissues, the net result of which is fuel storage. PHYSIOLOGICAL EFFECTS- Immediate within seconds effects include the modulation of potassium ion and glucose transport into the cell. early within minutes include the regulation of metabolic enzyme activity. Moderate within minutes to hours include the modulation of enzyme synthesis. Delayed within hours today's include the effects on growth and cellular differentiation. actions of insulin at Target organs are anabolic and promote the synthesis of carbohydrates fat and protein and these effects are mediated through binding to the insulin receptor. GO TO NOTES MORE INSULIN EFFECTS AT TARGET ORGANS GLUCAGON- the principal Target tissue for glucagon is the liver. Glucagons main physiological effect is to increase plasma glucose concentrations by stimulating de novo hepatic glucose production through gluconeogenesis and glycogen breakdown; overall, these actions counteract the effects of insulin.
Physiological actions adrenal cortical hormones.
Metabolism: Degrades muscle protein and increases nitrogen excretion Increases gluconeogenesis and plasma glucose levels Increases hepatic glycogen synthesis Decreases glucose utilization (anti-insulin action) Decreases amino acid utilization Increases fat mobilization Redistributes fat Permissive effects on glucagon and catecholamine effects
Understand the cellular mechanism of action of adrenal cortical hormones
Mineralocorticoids and glucocorticoids receptors share 57% homologies in the ligand binding domain and 94% homologies in the DNA binding domain. Once GC and MC bind to intracellular receptors, these dimerize prior to nuclear translocation and binding to DNA GC or MC responsive elements increasing or suppressing transcription of specific genes. Cortisol binds with high affinity to the MR and can produce MC like effects such as sodium attention. Cortisol conversion to Cortisone decreases the affinity for the MR receptor. Decreased activity of 11b-HSD2 the leads to decreased conversion of cortisol to Cortizone and increased and MC activity.
Identify the origin, target organs and cell types, and physiologic effects of parathyroid hormone.
Origin- parathyroid hormone made by chief cells (oxyphil cells purpose not fully understood); synthesized as a pre-propeptide - rapidly cleaved to yield pro-PTH and then the mature form of PTH (84 aa). Target organs- The major target end organs for parathyroid hormone (PTH) action are the kidneys, skeletal system (bone), and intestine. The primary response to parathyroid hormone (PTH) by the kidney is to increase renal calcium resorption and phosphate excretion. PHYSIOLOGICAL EFFECTS: Increases plasma calcium levels by increasing calcium renal absorption, calcium mobilization from bone, and intestinal absorption indirectly via D3 activation. Effects are mediated by binding to a cell membrane receptor in target organs. Three types of PTH receptors: PTHR1, PTHR2, PTHR3 (G-protein coupled receptors)
Identify the disease states caused by oversecretion, undersecretion, or decreased sensitivity to insulin, and describe the principal manifestations of each.
Oversecretion - Hypoglycemia (excess insulin), diabetic ketoacidosis (increased ketone bodies) Undersecretion - hyperglycemia Hyperinsulinemia is most often caused by insulin resistance — a condition in which your body doesn't respond well to the effects of insulin. Your pancreas tries to compensate by making more insulin. Insulin resistance may eventually lead to the development of type 2 diabetes (Decreased sensitivity to insulin). This happens when your pancreas is no longer able to compensate by secreting the large amounts of insulin required to keep the blood sugar normal. Rarely, hyperinsulinemia is caused by: A rare tumor of the insulin-producing cells of the pancreas (insulinoma) Excessive numbers or growth of insulin-producing cells in the pancreas (nesidioblastosis)
Describe the regulation of parathyroid hormone secretion and the role of the calcium sensing receptor.
PTH Release is increased by hypocalcemia, hyperphosphatemia, catecholamines PTH Release is suppressed by hypercalcemia, Vitamin D (inhibits gene transcription) Activation of PTH Ca2+ receptor leads to leukotriene production and degradation of performed PTH. Relaxed leads to unimpeded PTH secretion. PTH Release is also under regulatory control by phosphate and magnesium levels. Elevations in plasma phosphate levels increase pth secretion (decreasing phospholipase A2 activity and arachidonic acid formation removing the inhibitory effect on pth secretion). Hypophosphatemia markedly decreases pth mRNA. Plasma magnesium concentrations also regulate pth secretion in a similar manner to that of calcium. Plasma magnesium levels reflect those of calcium most of the time. The balance of magnesium is closely linked to that of calcium. Magnesium depletion or deficiency is frequently associated with hypocalcemia. The extracellular calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that is predominantly expressed in the parathyroids and kidneys, where it allows regulation of parathyroid hormone (PTH) secretion and renal tubular calcium reabsorption appropriate to the prevailing extracellular calcium ..
Describe the endometrial (proliferative and secretory phases) and ovarian events that occur throughout the menstrual cycle and correlate them with the changes in blood levels of pituitary and ovarian hormones.
The follicular phase begins on day 1 of the cycle, the first day of menses, and corresponds to the growth and development of a dominant follicle. During this phase, the dominant follicle produces high concentrations of 17βestradiol and inhibin B. Although initially estradiol exerts negative feedback on FSH and LH release, as concentrations of estradiol increase, toward the end of the follicular phase, a switch from negative to positive feedback occurs. High estradiol levels in the hypothalamus and pituitary lead to lowamplitude, highfrequency pulses (every 90 minutes) of LH, resulting in a midcycle LH surge. The estradiolmediated stimulation of the LH surge results from an increased responsiveness of gonadotropic cells to GnRH (following exposure to increasing estradiol levels), an increase in GnRH receptor number, and a GnRH surge, triggered by the effect on the hypothalamus of increasing estradiol concentrations. Inhibin B levels rise during the follicular phase and decrease immediately before the LH peak, with a brief surge occurring 2 days after ovulation. Inhibin A levels increase in the late follicular phase to reach a peak concentration on the day of the LH and FSH surge. The concentration then falls briefly before rising to reach a maximum concentration during the midluteal phase. The midcycle surge in LH levels induces ovulation, resumption of meiosis, and promotes the formation and survival of the corpus luteum during the luteal phase. During the luteal phase, high circulating concentrations of progesterone (produced by the corpus luteum) suppress the frequency and the amplitude of LH release, resulting in an overall decrease in LH by blocking the surges of GnRH, downregulating pituitary GnRH receptor expression, and decreasing gene expression of the α and βsubunits of both LH and FSH. Thus, negative feedback regulation by progesterone during the luteal phase prevents a second LH surge. The marked suppression of GnRH and LH pulse frequency achieved by high progesterone levels during the luteal phase allows enrichment of gonadotroph FSH levels. Inhibin B levels remain low during the luteal phase. Inhibin A is secreted by the granulosa cells during the luteal phase, and its concentration falls during luteal regression synchronously with estradiol and progesterone, remaining low during the early follicular phase.
Describe the regulation of mineralocorticoid secretion and relate this to the regulation of sodium and potassium excretion.
The main physiologic stimulus for aldosterone release is a decrease in the effective intravascular blood volume. 1- decline in blood volume leads to decreased renal perfusion pressure - sensed by the juxtaglomerular apparatus (baroreceptor) triggering the release of renin. 2- Renin catalyzes the conversion of angiotensinogen (derived from liver) to angiotensin I. 3- Circulating angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE), highly expressed in vascular endothelial cells. 4- Increased circulating angiotensin II produces a. direct arteriolar vasoconstriction, b. stimulates adrenocortical cells of the zona glomerulosa to synthesize and release aldosterone c. stimulates arginine vasopressin release from the posterior pituitary Potassium- also a major physiologic stimulus for aldosterone production, (classic example of hormone regulation by the ion it controls) Aldosterone is critical in maintaining potassium homeostasis by increasing K+ excretion in urine, feces, sweat, and saliva, preventing hyperkalemia during periods of high K+ intake or after K+ release from skeletal muscle during strenuous exercise. In turn, elevations in circulating K+ concentrations stimulate the release of aldosterone from the adrenal cortex. Aldosterone regulates mineral (sodium and potassium) balance - specifically renal potassium excretion and sodium reabsorption.
Describe the endocrine regulation of testicular function by gonadotropinreleasing hormone, follicle stimulating hormone, luteinizing hormone, testosterone, and inhibin.
The primary functions of the testes are to produce spermatozoa and to produce the hormones involved in the regulation of reproductive function and virilization. These functions are regulated by the pituitary gonadotropins FSH and LH. LH and FSH circulate unbound in the plasma and have a halflife of 30 minutes (LH) and 1-3 hours (FSH). LH has higher amplitude fluctuations in plasma than FSH; FSH levels are more stable and show less variability. Gonadotropin release from the anterior pituitary gland is controlled by the hypothalamic gonadotropinreleasing hormone (GnRH) pulse generator. Factors that stimulate GnRH release include norepinephrine (NE), neuropeptide Y (NPY), and leptin. Factors that inhibit GnRH release include βendorphin, interleukin 1 (IL1), γaminobutyric acid (GABA), and dopamine (DA) neurons. The activity of the pulse generator and the release of luteinizing hormone (LH) and folliclestimulating hormone (FSH) are regulated by the gonadal hormones testosterone and inhibin B and by locally produced factors such as activin. Activin interacts with inhibin B, thus increasing FSH βsubunit synthesis. The negative feedback regulation exerted by testosterone is mediated by local conversion to 17β estradiol. LH is the principal regulator of testosterone production by the Leydig cells. FSH plays an important role in the development of the immature testis, particularly by controlling Sertoli cell proliferation and seminiferous tube growth. Because the tubules account for approximately 80% of the volume of the testis, FSH is of major importance in determining testicular size, normally 4.1-5.2 cm in length and 2.5-3.3 cm in width in the adult male. FSH is important in the initiation of spermatogenesis during puberty. It is necessary for the production of androgenbinding protein (APB) by Sertoli cells and for the development of the bloodtestis barrier.
Describe the biological consequences of sympathoadrenal medulla activation (flight or fight response) and identify the target organs or tissues for catecholamine effects along with the receptor types that mediate their actions
The sympathetic nervous systems stimulate the adrenal glands triggering the release of catecholamines, which include adrenaline and noradrenaline. The physiological changes that occur during the fight or flight response are activated in order to give the body increased strength and speed in anticipation of fighting or running. ... Increased blood pressure, heart rate, blood sugars, and fats in order to supply the body with extra energy. catecholamines target alpha and beta- adrenergic receptors, a family of g protein coupled receptors (GPCRs). The physiologic effects of catecholamines are mediated by binding to cell membrane G protein-coupled adrenergic receptors distributed widely throughout the body (do not cross blood-brain-barrier). - differential effects depending on the subtype of G protein to which the receptor is associated with and the signal transduction mechanism linked to that specific G protein
Know the anatomical zones of the adrenal glands and the principal hormones secreted from each zone
The zona glomerulosa contains abundant smooth endoplasmic reticulum and is the unique source of the mineralocorticoid aldosterone. The zona fasciculata contains abundant lipid droplets and produces the glucocorticoids, cortisol and corticosterone, and the androgens, DHEA and DHEA sulfate (DHEAS). The zona reticularis develops postnatally and is recognizable at approximately age 3 years; it also produces glucocorticoids and androgens.
Describe the negative feedback relationship between parathyroid hormone and the biologically active form of vitamin D.
Vitamin D inhibits PTH secretion through decreasing its gene expression. A sudden decrease in Ca2+stimulates the release of PTH from the parathyroid gland. PTH increases the activity of 1α-hydroxylase in the kidney, leading to increased activation of vitamin D. In addition, PTH increases the reabsorption of Ca2+ and decreases the reabsorption of inorganic phosphate (Pi). In bone, PTH stimulates bone resorption, increasing the plasma Ca2+ levels. The elevations in vitamin D and plasma Ca2+ levels exert negative feedback inhibition of PTH release. Elevations in plasma Pi levels stimulate the release of PTH.
Identify the target organs and cellular mechanisms of action of vitamin D.
Vitamin D, synthesized in the skin or obtained from the diet, and PTH, secreted by the parathyroid glands, increase serum Ca2+ concentrations via actions on the gut, kidney and bone. The active form of vitamin D binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription.
