Unit 3 Study Guide NU 545 Hormonal Regulation PDF

Unit 3 Study Guide NU 545 **CHAPTER 21- Mechanisms of Hormonal Regulation** **Know which hormones are water soluble and which are lipid soluble.** +-----------------------------------+-----------------------------------+ | **WATER SOLUABLE HORMONES:** | **LIPID SOLUBLE HORMONES** | +=...

Unit 3 Study Guide NU 545 **CHAPTER 21- Mechanisms of Hormonal Regulation** **Know which hormones are water soluble and which are lipid soluble.** +-----------------------------------+-----------------------------------+ | **WATER SOLUABLE HORMONES:** | **LIPID SOLUBLE HORMONES** | +===================================+===================================+ | 1. Peptides | 1. Thyroxine (an amine but lipid | | | soluble)  | | a. Growth hormone | | | | a. Thyroxine (both thyroxine | | b. Insulin | \[T4\] and | | | triiodothyronine \[T3\]) | | c. Leptin | | | | 2. Steroids (cholesterol is a | | d. Parathyroid hormone | precursor for all steroids) | | | | | e. Prolactin | b. Estrogens | | | | | 2. Glycoproteins  | c. Glucocorticoids | | | (cortisol) | | f. Follicle-stimulating | | | hormone | d. Mineralocorticoids | | | (aldosterone) | | g. Luteinizing hormone | | | | e. Progestins (progesterone) | | h. Thyroid-stimulating | | | hormone | f. Testosterone | | | | | 3. Polypeptides  | 3. Derivatives of arachidonic | | | acid (autocrine or paracrine | | i. Adrenocorticotropic | action) | | hormone | | | | g. Leukotrienes | | j. Antidiuretic hormone | | | | h. Prostacyclins | | k. Calcitonin | | | | i. Prostaglandins | | l. Endorphins | | | | j. Thromboxanes | | m. Glucagon | | | | | | n. Hypothalamic hormones | | | | | | o. Lipotropins | | | | | | p. Melanocyte-stimulating | | | hormone | | | | | | q. Oxytocin | | | | | | r. Somatostatin | | | | | | s. Thymosin | | | | | | t. Thyrotropin-releasing | | | hormone | | | | | | 4. Amines  | | | | | | u. Epinephrine | | | | | | v. Norepinephrine | | +-----------------------------------+-----------------------------------+ **Know how protein hormones are transmitted in the blood.** 1. Once hormones are released into the circulatory system, they are distributed throughout the body. a. **Peptide or protein hormones** are **water-soluble and circulate in free (unbound) forms**. b. Water-soluble hormones i. have a short half-life because they are catabolized by circulating enzymes. ii. Insulin has a half-life of 3-5 minutes and is catabolized by insulinases. c. Lipid-soluble hormones (cortisol and adrenal androgens) are iii. transported bound to a carrier or transport protein iv. can remain in the blood for hours to days 2. Only free hormones can initiate changes within a target cell. d. Because equilibrium exists between the concentrations of free hormones and hormones bound to plasma proteins, a significant change in the concentration of binding proteins can affect the concentration of free hormones in the plasma. e. When a hormone is release into circulatory system, it is distributed throughout the body, but only those cells with appropriate hormone receptors for that hormone are affected. The target cell hormone receptors have two main functions v. To recognize and bind with high affinity to their particular hormones vi. To initiate a signal to appropriate intracellular effectors **What is oxytocin? How does it relate to the pituitary gland? Where is it secreted and what are its effects?** 1. Origin: Oxytocin is a polypeptide hormone synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. 2. Define: a. Oxytocin is implicated in behavior responses, especially in women b. Plays role in brains responsiveness to stressful stimuli, especially in the pregnant and postpartum states. 3. Relation to pituitary gland: the posterior pituitary secretes and stores oxytocin. c. Once synthesized, it is packaged in secretory vesicles along with its neurophysin and moved down the axons of the pituitary stalk to the pars nervosa for storage. d. Release of oxytocin is mediated by cholinergic and adrenergic neurotransmitters, and the major stimulus for release is glutamate. 4. Effects: Oxytocin is responsible for the contraction of the uterus and milk ejection in lactating women and may affect sperm motility in men. 5. Secreted in response to suckling and mechanical distention of female reproductive tract. e. Suckling Oxytocin bind to its receptors on myoepithelial cells in the mammary tissues and causes contract of those cells increases intramammary pressure and milk expression = "let down" reflex f. Distention of the uterus oxytocin stimulates contractions (functions as positive feedback loop to further increase oxytocin secretion); functions near the end of labor to enhance effectiveness of contractions, promote delivery of placenta, and stimulate postpartum uterine contractions (preventing excessive bleeding) **Know ADH. Where is it secreted? Where does it act?** **Major homeostatic function** of the posterior pituitary is the control of osmolality, which is regulated by ADH. 1. **Acts on** vasopressin 2 (V2) receptors of the renal tubular cells to increase their permeability, which leads to increased water absorption into the blood, concentrating the urine and reducing serum osmolality. a. Effects may be inhibited by hypercalcemia, prostaglandin E, and hypokalemia. **Causes of secretion of ADH** 1. The **secretion of ADH** (polypeptide hormone) is regulated by the osmoreceptors of the **hypothalamus**, located near or in the supraoptic nuclei. 2. **ADH secretion is increased**: a. **Plasma osmolality increases** osmoceptors are stimulated b. rate of ADH secretion increases c. more water is absorbed from kidney d. plasma is diluted to its set-point osmolality (approx. 280 mOsm/kg) i. ADH has no direct effect on electrolytes, but with *increased water absorption* *serum electrolytes may decrease* due to a dilutional effect. e. **Changes in intravascular volume**: ii. monitored by baroreceptors in the left atrium and in the carotid arteries and aortic arch volume loss of 7-25% stimulates receptors f. **Stress, trauma, pain, exercise, nausea, nicotine, exposure to hea**t, and **drugs** (**morphine**) **ADH secretion decreases** with a decrease in plasma osmolality, an increase in intravascular volume, hypertension, an increase in estrogen, progesterone, and angiotensin II levels, and alcohol ingestion. ADH does not affect vessel tone however, pathophysiological **high serum levels of ADH** acts on vasopressin I (V1) receptors vasoconstriction **increase in arterial blood pressure**. 1. Ex. Vasopressin may be given during hemorrhage to achieve homeostatic and raise blood pressure in shock states **Where are the target cells for each hormone located?** 1. Hypothalamus located at the base of the brain and contain connections that are vital to the functioning of the hypothalamic-pituitary system: a. Infundibulum pituitary gland b. Hypophysial portal blood vessels anterior pituitary c. Hypothalamohypophysial tract (nerve tract) posterior pituitary (ADH / oxytocin travel this way) 2. Hypothalamus contains neurosecretory cells synthesize & secrete hypothalamic-releasing hormones regulate release of hormones on the anterior pituitary and synthesize the hormones ADH and oxytocin (stored and released from the posterior pituitary gland) 3. Also synthesized in the hypothalamus are releasing/inhibitory hormones: PIH, PRH, TRH, GnRH, hypothalamic somatostain, GHRH, CRH, and substance P (See table 21.4 and 21.5) A diagram of the human body AI-generated content may be incorrect. Hormone Action ---------------------------------------------- -------------------------------------------------------------------------------------------------------------------------- Target the Anterior Pituitary for Release Thyrotropin-releasing hormone (TRH) Stimulates release of thyroid-stimulating hormone (TSH); modulates prolactin secretion Gonadotropin-releasing hormone (GnRH) Stimulates release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Somatostatin Inhibits release of growth hormone (GH) and TSH Growth hormone--releasing hormone (GHRH) Stimulates release of GH Corticotropin-releasing hormone (CRH) Stimulates release of adrenocorticotropic hormone (ACTH) and β-endorphin Substance P Inhibits synthesis and release of adrenocorticotropic hormone (ACTH); stimulates secretion of GH, FSH, LH, and prolactin Prolactin-inhibiting hormone (PIH, dopamine) Inhibits synthesis and secretion of prolactin Prolactin-releasing hormone (PRH) Stimulates secretion of prolactin Travel to Posterior Pituitary for Release Antidiuretic hormone (ADH) Increases water reabsorption through the renal collecting ducts to reduce plasma osmolarity Oxytocin Stimulates contraction of the uterus and milk ejection in lactating women +-----------------------+-----------------------+-----------------------+ | Tropic Hormones of | | | | the Anterior | | | | Pituitary and Their | | | | Functions | | | +=======================+=======================+=======================+ | Hormone | Target Organs | Functions | +-----------------------+-----------------------+-----------------------+ | Corticotropin-Related | | | | Hormones | | | +-----------------------+-----------------------+-----------------------+ | Adrenocorticotropic | Adrenal gland | Increased | | hormone (ACTH) | (cortex) | steroidogenesis | | | | (cortisol and | | | | androgenic hormones); | | | | synthesis of adrenal | | | | proteins contributing | | | | to maintenance of | | | | adrenal gland | +-----------------------+-----------------------+-----------------------+ | Melanocyte-stimulatin | Anterior pituitary | Promotes secretion of | | g | | melanin and | | hormone (MSH) | | lipotropin by | | | | anterior pituitary; | | | | makes skin darker | +-----------------------+-----------------------+-----------------------+ | Somatotropic Hormones | | | +-----------------------+-----------------------+-----------------------+ | Growth hormone (GH) | Muscle, bone, liver | Regulates metabolic | | | | processes related to | | | | growth and adaptation | | | | to physical and | | | | emotional stressors, | | | | muscle growth, | | | | increased protein | | | | synthesis, increased | | | | liver glycogenolysis, | | | | increased fat | | | | mobilization | +-----------------------+-----------------------+-----------------------+ | Liver | Induces formation of | | | | somatomedins, or | | | | insulin-like growth | | | | factors (IGFs) that | | | | have actions like | | | | insulin | | +-----------------------+-----------------------+-----------------------+ | Prolactin | Breast | Milk production | +-----------------------+-----------------------+-----------------------+ | Glycoprotein Hormones | | | +-----------------------+-----------------------+-----------------------+ | Thyroid-stimulating | Thyroid gland | Increased production | | hormone (TSH) | | and secretion of | | | | thyroid | | | | hormoneIncreased | | | | iodide uptake; | | | | promotes hypertrophy | | | | and hyperplasia of | | | | thymocytes | +-----------------------+-----------------------+-----------------------+ | Luteinizing hormone | In women: granulosa | Ovulation, | | (LH) | cells | progesterone | | | | production | | | In men: Leydig cells | | | | | Testicular growth, | | | | testosterone | | | | production | +-----------------------+-----------------------+-----------------------+ | Follicle-stimulating | In women: granulosa | Follicle maturation, | | hormone (FSH) | cells | estrogen production | | | | | | | In men: Sertoli cells | Spermatogenesis | +-----------------------+-----------------------+-----------------------+ | β-Lipotropin | Adipose cells | Fat breakdown and | | | | release of fatty | | | | acids | +-----------------------+-----------------------+-----------------------+ | β-Endorphins | Adipose cells; brain | Analgesia; may | | | opioid receptors | regulate body | | | | temperature, food and | | | | water intake | +-----------------------+-----------------------+-----------------------+ **What is the role of calcitonin?** **Controlled by Thyroid gland (secreted by C cells);** also called *thyrocalcitonin*, it acts to **lower serum calcium levels by inhibition of** **bone-resorbing osteoclasts**. High levels of calcitonin are required for these effects, and deficiencies of calcitonin do not lead to hypocalcemia. 1. The metabolic consequences of calcitonin deficiency or excess do not appear to be significant in humans. 2. **Calcitonin** is used to treat: *osteoporosis*, *osteoarthritis*, *Paget bone disease*, *hypercalcemia*, osteogenesis imperfecta, and metastatic cancer of the bone. 3. Procalcitonin: Precursor molecule to calcitonin, is a stress hormone that is elevated in infectious and inflammatory disorders and its measurement can aid in the diagnosis of these serious diseases. Etiology: produced by parafollicular cells of thyroid. Patho: elevated serum calcium and gastrin are major stimulates for calcitonin. Decreased calcium suppresses calcitonin release. 1. CalcitonIN brings calcium back IN into the bone a. Calcitonin opposes PTH 2. OsteoBLASTS b. take calcium from the blood stream puts it back in the bone 3. OsteoCLASTS c. Calcitonin receptors are on osteoCLASTS d. make the bone crash (take calcium from bone to blood stream) = stopping osteoclasts stops calcium from being put into the blood stream bone breakdown ceases +-----------------------+-----------------------+-----------------------+ | Hormone | Regulation | Functions | +=======================+=======================+=======================+ | Calcitonin | Elevated serum | Lowers serum calcium | | | calcium---major | by opposing | | | stimulant for | bone-resorbing | | | calcitonin | effects of PTH, | | | | prostaglandins, and | | | Other stimulants | calciferols by | | | | inhibiting | | | Gastrin | osteoclastic activity | | | | | | | Calcium-rich foods | Lowers serum | | | (regardless of serum | phosphate levels | | | Ca++ levels) | | | | | May also decrease | | | Pregnancy | calcium and | | | | phosphorus absorption | | | Lowered serum | in GI tract | | | calcium---suppresses | | | | calcitonin release | | +-----------------------+-----------------------+-----------------------+ **What is the role of TSH? Where is it secreted? Know the negative feedback loop.** 1. Define: thyroid stimulating hormone (TSH) is a glycoprotein hormone synthesized and stored within the anterior pituitary a. Anterior pituitary secretes TSH (from cells called thyrotrophs) binds with TSH receptor sites located on plasma membrane of thyroid follicular cells 2. The role of TSH on the thyroid gland include: b. an immediate increase in the release of stored thyroid hormones c. an increase in iodide uptake and oxidation d. an increase in thyroid synthesis e. an increase in the synthesis and secretion of prostaglandins by the thyroid f. increases growth of the thyroid gland by stimulating thymocyte hyperplasia, hypertrophy, and decreasing apoptosis 3. Negative feedback loop: g. Anterior pituitary releases TSH stimulates synthesis of TH thyroid hormone rises negative-feedback effect on the HPA inhibition of TRH release of TSH decrease TH synthesis and secretion  **What is parathyroid hormone? What are the effects of PTH?** 1. **Define:** single most important factor in regulation of serum calcium concentration 2. **Etiology:** produced by parathyroid glands 3. **Role of PTH:** increase serum calcium concentration and decrease the concentration of serum phosphate 4. **Patho:** a decrease in serum serum-ionized calcium level stimulates PTH secretion PTH enters the circulation in unbound form attaches to plasm membrane receptors on target tissues and mediated by activation of the adenylyl cyclase system a. PTH acts directly on bones i. Acute hypocalcemia PTH secreated stimulates osteoblasts to release receptor activator for nuclear factor (NF-kb), receptor activator (RANKL), and macrophage-colony stimulating factor (M-CSF) osteoclast proliferation, maturation, and release of acidic enzymes (capthepsin) mobilize calcium release from bone (bone resorption) ◊ increases serum calcium level 1. Chronic stimulation by PTH results in bone remodeling b. PTH acts directly on kidney = increase calcium reabsorption while phosphate reabsorption is decreased ii. PTH acts on plasma membrane receptor in distal tubules of the nephron increase reabsorption of calcium increase in serum calcium concentration inhibits PTH secretion iii. PTH acts on the proximal tubules to decrease reabsorption of phosphorus and bicarbonate A diagram of a complex of vitamins AI-generated content may be incorrect. **Know the relationship between calcium and phosphorus** 1. **Phosphorus** mineral that combines with calcium to form the hard structure of your bones and teeth (comes from food). Phosphate is found in all cells in your body and is absorbed with help from Vitamin D 2. **Calcium** stored in your bones; calcium levels are too low, then your body will take the extra calcium it needs from your bones. 3. **Hyperphosphatemia** leads to hypocalcemia because of calcium phosphate precipitation in soft tissue and bone. Alterations in serum phosphate levels therefore may indirectly influence PTH secretion by affecting serum calcium levels. **Understand the role of insulin, how does insulin affect potassium.** **Role of insulin:** anabolic hormone that promotes glucose uptake primarily in liver, muscle, and adipose tissue and increases the synthesis of proteins, carbohydrates, lipids, and nucleic acids **Etiology:** beta cells of the pancreas synthesize insulin (from the precursor proinsulin) Secretion is regulated by chemical, hormonal, and neural control 1. **Increase in Insulin secretion:** a. Beta cells are stimulated by the parasympathetic nervous system (usually before eating a meal) b. Increased blood levels of glucose, amino acids (leucine, argine, and lysine) and GI hormones (glucagon, gastrin, cholecystokinin, secretin) 2. **Decrease in Insulin secretion:** c. Response to low blood levels of glucose (hypoglycemia) d. High levels of insulin (negative-feedback to the beta cells) e. Sympathetic stimulation of the beta cells in the islets f. Prostaglandins also inhibit insulin secretion **Effect of insulin on potassium:** facilitates the *intracellular transport of potassium (K+)*, phosphate, and magnesium **Insulin Actions** --------------------- ----------------------------------------- ----------------------------- ------------------------------ **Actions** **Sites of insulin-promoted synthesis** **Liver Cells** **Muscle Cells** **Adipose Cells** Glucose uptake Increased Increased Increased Glucose use \-\-- \-\-- Increased glycerol phosphate Glycogenesis Increased Increased \-\-- Glycogenolysis Decreased Decreased \-\-- Other Increased fatty acid synthesis Increased amino acid uptake Increased fat esterification Decreased ketogenesis Increased protein synthesis Decreased lipolysis Decreased urea cycle activity Decreased proteolysis Increased fat storage **What is aldosterone and why do we need it?** **Aldosterone** is the most potent of the naturally occurring mineralocorticoids and acts to conserve sodium by increasing the activity of the sodium pump of the epithelial cells in the nephron. Initial stages of aldosterone synthesis occur in the adrenal zona fasciculata and zona reticularis final conversion of corticosterone to aldosterone occurs in the zona glomerulosa Renin-angiotensin-aldosterone system regulates aldosterone -- activated by: 1. activated by sodium and water depletion 2. increased potassium levels 3. diminished effective blood volume **Angiotensin II (**primary stimulant of aldosterone synthesis and secretion) \*\*however, serum potassium concentration directly stimulates aldosterone secretion and ACTH acutely stimulates aldosterone secretion (secondary to angiotensin II and potassium) **Feedback Mechanisms Regulating Aldosterone Secretion:** 1. When Na+ and K+ levels are WNL approximately 50-250 mg of aldosterone is secreted daily (50% to 75% binds to plasma proteins 2. Aldosterone maintains extracellular volume by acting on distal nephron epithelial cells to increase sodium+ reabsorption, and potassium and hydrogen excretion (renal effect takes 90 minutes -- 6 hours) a. Aldosterone is degraded in the liver and is excreted by the kidney Other effects of aldosterone include: 1. enhancement of cardiac muscle contraction 2. stimulation of ectopic ventricular activity through secondary cardiac pacemakers in the ventricle, stiffening of blood vessels with increased vascular resistance, and decreased fibrinolysis. \*\*Elevated levels of aldosterone implicated in myocardial changes associated with heart failure.  **Understand the roles of epinephrine and norepinephrine.** Adrenal medulla chromaffin cells (pheochromocytes) store and secrete epinephrine and norepinephrine both are synthesized from the amino acid phenylalanine (30% of circulating epinephrine comes from adrenal medulla, 70% is released from nerve terminals; the medulla is only a minor source of norepinephrine) Epinephrine and Norepinephrine are both categorized as water soluble amines [Physiologic stress to the body] 1. In traumatic injury, hypoxia or hypoglycemia Acetylcholine (from preganglionic sympathetic fibers) Triggers release of adrenal catecholamines Depolarizes chromaffin cells Exocytosis of storage granules from the chromaffin cells Release epinephrine and norepinephrine into bloodstream \[therefore, catecholamines from the adrenal medulla are hormones and not neurotransmitters\] a. ACTH and glucocorticoids increase secretion of adrenal catecholamines 2. Catecholamines remain in plasms for seconds -- minutes exert rapid biologic effects after binding to plasma membrane receptor in target cells activates adenylyl cyclase system neurons rapidly remove catecholamines from plasma stored in new cytoplasmic granules or metabolically inactivate and excrete in the urine Catecholamines have diverse effects on the entire body 1. Their release and the body's response have been characterized as the "fight or flight" response 2. Effects of catecholamines activate adrenergic receptors on cell membranes of ALL visceral organs and smooth muscles and promote hyperglycemia [From hormone function chart:] Epinephrine increases heart rate, oxygen intake and blood flow Norepinephrine maintains blood pressure