Endocrine and Reproductive Physiology Lectures 52-66 PDF

ENDOCRINE AND REPRO PHYSIOLOGY -- LECTURES 52-66 ================================================ **[Lecture 52 - Principles of Endocrinology]** - Describe the four classes of hormones and how each is synthesized, stored, secreted and metabolized. - Interpret a chang...

ENDOCRINE AND REPRO PHYSIOLOGY -- LECTURES 52-66 ================================================ **[Lecture 52 - Principles of Endocrinology]** - Describe the four classes of hormones and how each is synthesized, stored, secreted and metabolized. - Interpret a change in a dose-response curve. - Depending on the class of hormone, predict which one will have the longest or shortest half-life. - See above table - Binding leads to a longer half life **[Lecture 53 - Hormones of the Endocrine Pancreas]** - Explain insulin's and glucagon's major metabolic actions. - High blood glucose stimulates insulin, which increase glucose uptake into the cells and converts glucose to glycogen - Insulin is essential for maintaining blood glucose homeostasis. It lowers blood glucose by facilitating its uptake into cells, promoting its storage as glycogen or fat, and inhibiting glucose production. In addition to regulating glucose, insulin also affects fat storage, protein synthesis, and electrolyte balance. - Low blood sugar stimulates glucagon, which converts glycogen to glucose - Glucagon is a critical hormone for increasing blood glucose during fasting or between meals. It does this by stimulating glycogen breakdown, glucose production, and fat breakdown. - List the physiological effects of insulin administration. - Insulin administration plays a crucial role in regulating blood glucose and supporting nutrient storage, particularly during the fed state. It promotes glucose uptake, glycogen storage, lipogenesis, and protein synthesis, while inhibiting processes like glycogen breakdown, gluconeogenesis, and lipolysis. - Increase uptake of glucose in the liver and muscles - Decrease the activity of hormone sensitive lipase - List the effects that insulin deficiency has on glucose, protein and fat metabolism. - Leads to prolonged elevation in plasma glucose due to decreased glucose uptake into the cells - Increases protein catabolism and amino acids in the blood - Increase lipolysis, leading to an increase in glycerol, fatty acids, and consequently, ketoacids **[Lecture 54 - Calcium and Phosphate Regulating Hormones]** - Describe how vitamin D3 is synthesized, stored, secreted, and regulated and explain vitamin D3's major actions. - Synthesized - First, hydroxylation occurs in the liver to lead to the formation of 25(OH)D or calcidiol. - Then, hydroxylation occurs in the kidneys and constitutes calcitriol - This is the primary regulated step - 1α-hydrolylase - Activity is increased by decreased plasma Ca^2+^, decreased plasma phosphate, and increased PTH - Stored in the liver and fat - Secreted in response to decreased plasma Ca^2+^ - Action: Stimulate Ca^2+^ and phosphate absorption in the intestines and kidneys and resorption of old bone mineralization of new bone - Diagnose a disease of calcium-sensing receptor mutation and list the expected effects on blood and urine levels of calcium and phosphate. - Familial Hypocalciuric Hypercalcemia (FHH): Caused by mutations in the CaSR (chief cells), leading to hypercalcemia, hypocalciuria, and normal or slightly elevated phosphate levels. - Increase in PTH, serum Ca^2+^, and urine phosphate - Decrease in serum phosphate and urine Ca^2+^ - Remember PTH is "Phosphate Trashing Hormone" - Know the major actions of all calcium and phosphate regulating hormones and determine the major mode of action for each. - PTH - Stimulate Ca^2+^ and phosphate absorption in the intestines and resorption of old bone, and reabsorption of only Ca^2+^ at the kidneys - Stimulated due to decreased plasma Ca^2+^ - Vitamin D - Stimulate Ca^2+^ and phosphate absorption in the intestines and kidneys and resorption of old bone mineralization of new bone - Stimulated due to decreased plasma Ca^2+^ - Calcitonin - Decreases blood calcium -- "Calci-tone-it-down"; less bone reabsorption - Stimulated due to elevated plasma Ca^2+^ **[Lecture 55 - Hypothalamic Neurohypophyseal Axis]** - Recognize the second messenger systems that are activated when ADH binds to its receptor. - V2 Receptor Activation (cAMP pathway) in the kidneys is responsible for ADH\'s primary effect of increasing water reabsorption and concentrating urine. - KIDNEYS - V1 Receptor Activation (IP3/Ca^2+^ pathway) mediates the vasoconstrictive effects of ADH, which helps regulate blood pressure by constricting blood vessels. - VASCULAR SMOOTH MUSCLE - Thus, the cAMP pathway through V2 receptors is essential for ADH\'s action on water balance, while the IP3/Ca^2+^ pathway through V1 receptors is important for the regulation of vascular tone and blood pressure. - Describe the pathologies associated with hyper- or hyposecretion of ADH and evaluate in a patient where the problem originates. - Hypersecretion of ADH (e.g., SIADH) results in water retention, hyponatremia, and hypoosmolality, with elevated urine osmolality. - Hyposecretion of ADH (e.g., diabetes insipidus) causes polyuria, polydipsia, and hypernatremia, with low urine osmolality. Depending on the etiology, it can be caused by problems with ADH production (central DI) or ADH resistance (nephrogenic DI). - Recognize the consequences of the inability to transport oxytocin and ADH and know the physiologic effects that occur with deficiencies in both. - ADH Deficiency (Diabetes Insipidus): Causes polyuria, polydipsia, hypernatremia, and dehydration due to impaired water reabsorption in the kidneys. Central DI arises from lack of ADH production, while nephrogenic DI results from kidney resistance to ADH. - Oxytocin Deficiency: Causes labor complications, failure of milk let-down, and possible social bonding issues. Oxytocin is essential for uterine contraction during childbirth and milk ejection during lactation. - Both hormones are critical for normal physiological function, and deficiencies can have a profound impact on reproductive health, fluid balance, and social and emotional well-being. **[Lecture 56 - Hypothalamic Adenohypophyseal Axis]** - Recognize how GH is regulated. - The secretion of growth hormone (GH) is tightly regulated by a variety of factors, including hypothalamic control via GHRH and somatostatin, negative feedback from IGF-1, and responses to circadian rhythms, exercise, nutritional status, and stress. - Stimulated by GHRH - Inhibited by Somatostatin and hyperglycemia - Recognize the major actions of prolactin. - Mammogenesis -- Growth and development of the mammary gland - Lactogenesis -- Initiation of lactation; increase synthesis of lactose, casein, and lipids - Define the physiological effects that occur with congenitally low growth hormone levels. - Pituitary Dwarfism - Failure to grow, but proportionate - Mild obesity - Normal IQ - Deficiency can also result in short stature and delayed puberty - NOT Laron Dwarf -- mutation in GH receptor **[Lecture 57 - Hypothalamic-Pituitary-Thyroid Axis]** - Know that propylthiouracil is a thyroid peroxidase inhibitor and list its physiologic effects. - Propylthiouracil (PTU) is an effective antithyroid drug that works by inhibiting thyroid peroxidase and reducing the synthesis of thyroid hormones (T3 and T4). It also inhibits the peripheral conversion of T4 to T3. By reducing thyroid hormone levels, PTU helps to manage hyperthyroidism and its associated symptoms such as tachycardia, weight loss, and heat intolerance. However, PTU is associated with potential adverse effects, including hepatotoxicity, agranulocytosis, and hypothyroidism, making careful monitoring necessary during treatment. - Decrease T3 and T4 formation and decrease T4 to T3 conversion - List the physiologic effects of excess thyrotropin-releasing hormone. - Excess thyrotropin-releasing hormone (TRH) can lead to hyperthyroidism due to the overproduction of TSH and thyroid hormones, resulting in a wide range of symptoms, including weight loss, heat intolerance, tachycardia, goiter, gastrointestinal disturbances, and reproductive issues like infertility. - Determine how exogenous thyroid hormone impacts the hypothalamic-pituitary-thyroid axis. - Exogenous thyroid hormone, such as levothyroxine (T4), levotriiodothyronine (T3), or combination therapies, exerts significant effects on the hypothalamic-pituitary-thyroid axis by suppressing TRH and TSH secretion through negative feedback. This suppression reduces the need for the thyroid to produce its own hormone, and when properly dosed, it helps normalize thyroid function in hypothyroid patients. However, excessive thyroid hormone replacement can suppress TSH too much, leading to potential hyperthyroidism and associated risks, requiring careful monitoring of serum TSH levels during therapy. **[Lecture 58 - Adrenal Cortex - Mineralocorticoids]** - Discuss consequences associated with hyper- or hyposecretion of mineralocorticoids. - The secretion of mineralocorticoids, particularly aldosterone, is critical for maintaining electrolyte balance, fluid volume, and blood pressure. Both hypersecretion and hyposecretion of aldosterone can lead to serious consequences: - Hypersecretion (e.g., Conn\'s syndrome) typically results in hypertension, hypokalemia, and metabolic alkalosis due to excessive sodium retention and potassium excretion. - Hyposecretion (e.g., Addison\'s disease) leads to hypotension, hyperkalemia, hyponatremia, - List the pathophysiologic effects of 21 beta-hydroxylase deficiency and determine which is most life threatening. - Increase in synthesis of adrenal androgens, precocious puberty, early appearance of secondary sex characteristics - Deficiency of cortisol -- hypoglycemia, hypotension, rapid growth, early completion short - Deficiency of aldosterone -- hypovolemia, hypotension, hyperkalemia, metabolic acidosis - List the physiologic effects of 11 beta-hydroxylase deficiency. - 11β-hydroxylase deficiency results in cortisol deficiency, mineralocorticoid excess, and androgen excess. The most prominent clinical features include virilization in females, precocious puberty in males, hypertension, hypokalemia, and metabolic alkalosis due to the accumulation of mineralocorticoid precursors like 11-deoxycorticosterone. Cortisol deficiency also increases the risk of adrenal crisis and hypoglycemia. Early diagnosis and appropriate treatment with glucocorticoids and anti-androgens are critical for managing the condition and preventing long-term complications. **[\ ]** **[Lecture 59 - Adrenal Cortex - Glucocorticoids]** - Describe actions of glucocorticoids. - Cortisol - Stimulation of gluconeogenesis - Inhibition of bone formation - Anti-inflammatory effects - Suppression of the immune response - Maintenance of vascular responses to catecholamines - CNS: decrease REM sleep, increase awake time, can cause insomnia - Predict the negative feedback effects of Cushings syndrome or Cushings disease. - In both Cushing\'s syndrome and Cushing\'s disease, the body\'s normal negative feedback mechanisms are disrupted, leading to persistently elevated cortisol levels. - In Cushing\'s disease (pituitary adenoma), the pituitary tumor produces excess ACTH, which results in high cortisol levels and impaired negative feedback. The pituitary and hypothalamus continue to secrete ACTH and CRH despite high cortisol levels. - In Cushing\'s syndrome, there is low ACTH due to adrenal tumor or excess exogenous glucocorticoids - Interpret results of the dexamethasone suppression test. **[Lecture 60 - Adrenal Medulla - Catecholamines]** - Diagnose pheochromocytoma. - Secretes hormones in bursts, so a 24-hour collection is needed. - Pheochromocytoma should be suspected in patients with episodic hypertension, palpitations, sweating, and other associated symptoms. - The most sensitive test for diagnosis is plasma free metanephrines. - Know what enzyme initiates catecholamine formation. - The initial step in catecholamine synthesis, and the rate-limiting step, is catalyzed by tyrosine hydroxylase, which converts tyrosine to L-DOPA, setting the stage for the production of dopamine, norepinephrine, and epinephrine. - Diagnose pheochromocytoma and name the initial line of therapy to control blood pressure. - Sx: adrenal mass, hot flashes, increase BP - First line treatment is phenoxybenzamine, which is an α~1~-adrenergic antagonist - Second line treatment is propranolol, a β-adrenergic antagonist **[\ ]** **[Lecture 61 - Hypothalamo-Pituitary-Gonadal Axis]** - Identify and discern how sex steroids are synthesized and regulated. - Synthesis of Sex Steroids: - Sex steroids (estrogens, androgens, and progesterone) are synthesized from cholesterol via enzymatic steps, with key enzymes such as cholesterol desmolase, 3β-HSD, 17α-hydroxylase, and aromatase playing major roles. - Regulation: - The synthesis of sex steroids is regulated by the HPG axis, where GnRH from the hypothalamus stimulates the pituitary to release LH and FSH, which in turn regulate the gonads to produce testosterone, estradiol, and progesterone. - Distinguish between primary and secondary pathologies related to hyper- and hypogonadism. - A close-up of a text Description automatically generated - Identify and discern how the sex steroids (testosterone, estrogen, progesterone) are synthesized, stored, secreted, and regulated. - Testosterone, estrogen, and progesterone are synthesized from cholesterol via enzymatic pathways involving cholesterol desmolase, 3β-HSD, 17α-hydroxylase, and aromatase. - Testosterone is primarily synthesized in the Leydig cells of the testes and adrenal glands, estradiol in the granulosa cells of the ovaries, and progesterone in the corpus luteum (ovaries). - Secretion occurs in response to GnRH, LH, and FSH secreted by the pituitary gland. - Regulation of these hormones is controlled by negative feedback loops and, in females, positive feedback during the menstrual cycle. - Their physiological effects are essential for reproduction, sexual development, and maintenance of bone and metabolic health. **[\ ]** **[Lecture 62 - Sexual Differentiation]** - Recognize general steps in sexual differentiation during embryonic development, recognize hormonal control in development of reproductive system. - Presence of the SRY gene leads to the testes - Sertoli cells produce anti-müllerian hormone - Leydig cells produce testerone - Wolfian ducts develop into male external genitalia due to testosterone - Dihydrotestoestrone leads to the devolpment of penis, scrotum, and prostate - Absence of the SRY gene leads to formation of the ovaries - Mullerian ducts develop into the fallopian tube and uterus - Determine the consequences of improper sexual differentiation and predict the outcome of the gonads, and internal and external genitalia. Predict result of abnormal hormone production during development. Determine the specific pathology associated with improper sexual differentiation given a clinical scenario. - Determine the consequences of improper sexual differentiation and predict the outcome of the gonads, and internal and external genitalia and predict result of abnormal hormone production during development. - See PPT **[Lecture 63 - Male Reproductive Physiology]** - Recognize steps of spermatozoa production and identify storage and delivery pathways, function of glands. - Seminiferous tubules produce sperm ( rete testes efferent ducts) - Epididymis and Vas deferns serve as the storage site - Ejaculatory duct prostate gland urethra is the delivery pathway - Identify how the ANS controls erection and ejaculation. - PNS -- erection - SNS -- ejaculation - Recognize the sequence of events involved in fertilization. - Fusion of egg and sperm in ampulla of fallopian tube within 24-48 hours of ovulation - Capacitation -- Removal of cholesterol coating that surrounds sperm to enable release of acrosomal enzymes & enhanced motility - Acrosome Reaction -- Release of enzymes from acrosome break down zona pellucida and initiates cortical reaction - Block to Polyspermy -- Fast - sodium influx = temporary depolarization, prevents additional sperm from binding. Slow - calcium influx = permanent initiates cortical reaction - Cortical Reaction -- inactivation of sperm-binding receptors on zona pellucida and hardening of zona pellucida, mediated by enzymes released from egg by exocytosis. Stops sperm from advancing and additional sperm from binding **[Lecture 64 - Female Reproduction I]** - Recognize and interpret hormonal changes during the ovarian cycles. (*Listed twice)* - - Recognize and discern steps in follicle maturation; recognize and interpret hormonal control of follicle maturation. - Follicle Development: - Follicles start as primordial follicles and go through the primary, secondary, and tertiary (antral) stages before becoming the Graafian (mature) follicle. - This process involves proliferation of granulosa cells, the formation of the antral space, and the accumulation of estrogen. - Hormonal Regulation: - FSH stimulates the growth of follicles and granulosa cell activity, leading to estrogen production. - LH contributes to the final maturation of the dominant follicle and triggers ovulation through the LH surge. - Estrogen promotes follicle growth and positive feedback for the LH surge, while also exerting negative feedbackto control hormone levels. - Inhibin and progesterone also play roles in feedback regulation. - Ovulation: The LH surge leads to the rupture of the mature follicle and the release of the oocyte.  **[Lecture 65 - Female Reproduction II]** - Recognize and interpret ovarian and uterine phases/events during the ovarian & menstrual cycles. - - Recall and interpret hormonal control of mammary gland development, lactogenesis, and control of lactation. - - Lactation is inhibited in pregnancy by estrogen and progesterone - Prolactin allows for milk production - Suckling inhibits dopamine, leading to increased prolactin - Oxytocin is responsible for milk letdown (ejection) - Recognize hormonal changes that occur with menopause and discern premenopausal and postmenopausal hormone profiles. - Decrease in estradiol and progesterone - Elevated LH and FSH **[\ ]** **[Lecture 66 - Physiology of Pregnancy]** - Recall the three stages of parturition and explain how parturition is hormonally controlled. - Dilation: Contractions increase in force and number - Expulsion: Lasts about an hour and is the forcing of the fetus from mother's body - Placental: lasts about 10 minutes and is the expulsion of the placenta - Estrogen starts the weak/infrequent contractions \~30 weeks; increases oxytocin receptors - Oxytocin has a positive feedback loop to increase uterine contractions - Recognize the placenta as a transient endocrine organ and recall the hormones it can produce. - Secretes estrogens (estriol), progesterone, relaxin, hCG, placental lactogen - hCG is secreted from the trophoblasts, highest in early pregnancy - hCS is also secreted from the trophoblasts - In later pregnancy, prolactin, progesterone, and estriol are higher (in that order) - Placenta must extract DHEA-S from mother or fetus to produce androgens - Recognize events during fertilization and implantation, early embryonic development, development of placenta, including timing of specific events. 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