Endocrinology - 2 Content

Endocrinology-2 Content Endocrinology • Posterior Pituitary • Oxytocin • Anti diuretic Hormone • Thyroid Gland • Parathyroid Gland Posterior Pituitary • Does not synthesize hormones but stores and releases them. • Composed of axons and axon terminals from hypothalamic neurosecretory cells. • Neurosecretory cell bodies are in the paraventricular and supraoptic nuclei of the hypothalamus. • Axons form the hypothalamic-hypophyseal tract. • Synthesizes oxytocin (OT) and antidiuretic hormone (ADH or vasopressin). Pituicytes • Specialized neuroglia in the posterior pituitary. • Have a supporting role similar to astrocytes. Blood Supply • Inferior hypophyseal arteries supply blood to the posterior pituitary. • Inferior hypophyseal arteries drain into the capillary plexus of the infundibular process. • Hormones (oxytocin and ADH) pass into hypophyseal veins for distribution to target cells. Posterior Pituitary Posterior Pituitary Secretion Posterior Pituitary Secretion 1. Neurosecretory cells in the paraventricular and supraoptic nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH). 2. The hormones are then packaged into vesicles. 3. The vesicles move by fast axonal transport along the hypothalamic–hypophyseal tract to the axon terminals in the posterior pituitary. 4. When the appropriate stimulus excites the hypothalamus, nerve impulses trigger exocytosis and release of oxytocin or ADH into the bloodstream (inferior hypophyseal artery, capillary plexus of the infundibular process, and hypophyseal vein). 5. The released oxytocin or ADH then travels to its target tissues in the body. Oxytocin (Love hormone) • During and after delivery of a baby, oxytocin affects two target tissues: the mother’s uterus and breasts. • During delivery, stretching of the cervix of the uterus stimulates the release of oxytocin and enhances contraction of smooth muscle cells in the wall of the uterus. • After delivery, it stimulates milk ejection (“letdown”) from the mammary glands in response to the mechanical stimulus provided by a suckling infant. • The function of oxytocin in males and in non-pregnant females is not clear. • It may also be responsible, in part, for the feelings of sexual pleasure during and after intercourse. Antidiuretic hormone (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH₂) Function of ADH • ADH decreases urine production by causing the kidneys to reabsorb more water, resulting in decreased urine volume. • In the absence of ADH, urine output increases significantly. • Alcohol inhibits ADH secretion, leading to frequent urination and dehydration. Effects on Blood Pressure • ADH also constricts arterioles (small arteries), increasing blood pressure. • Its other name, vasopressin, reflects this effect on blood pressure regulation. Stimuli for ADH Secretion • Rise in blood osmolarity: Detected by osmoreceptors in the hypothalamus. • Decrease in blood volume: Detected by volume receptors in the heart atria and baroreceptors in blood vessel walls. Target Tissues • ADH acts on the kidneys, promoting water reabsorption. • It also affects smooth muscle in arterioles, leading to vasoconstriction. Other Factors Affecting ADH Secretion • Pain, stress, trauma, anxiety, acetylcholine, nicotine, and certain drugs can stimulate ADH release. Vedemy Capsule Parameter Oxytocin Vasopressin Hormone Target Site Uterus, mammary glands Kidneys, blood vessels Target Receptor Oxytocin receptor (OTR)/GPCR Vasopressin receptor (V1aR)/V2 receptor (GPCR) Regulation • Positive feedback • During childbirth, oxytocin initiates uterine contractions and increases as contractions intensify, leading to delivery. It also facilitates milk ejection during breastfeeding. Oxytocin is linked to social bonding, released during positive interactions, promoting trust, empathy, and emotional connection. Negative feedback • Blood osmolality rises → Hypothalamus detects → Stimulates posterior pituitary to release vasopressin → Vasopressin acts on kidneys → Promotes water reabsorption, reduces urine volume → Vasopressin secretion decreases as osmolality normalizes. • Low blood pressure → Increased vasopressin secretion → Vasoconstriction → Maintains blood pressure. • High blood pressure → Decreased vasopressin secretion. Molecular Weight ~1007 Da ~1084 Da Function Milk ejection, social bonding Water reabsorption, vasoconstriction Activating Cascade Phospholipase C (PLC) pathway Phospholipase C (PLC) pathway Mechanism of Action Oxytocin binds to OTR, leading to uterine contractions and milk ejection. It also promotes social bonding. Vasopressin binds to V1aR, causing vasoconstriction and water reabsorption. It also influences social behavior. Vedemy Capsule Endocrine Gland Pituitary (anterior) Hormone Growth hormone (GH) Prolactin (PRL) Thyroidstimulating hormone (TSH) Chemical Class Effects Receptor Types Peptide Promotes growth of body tissues JAK STAT (cytokine receptor) Peptide Promotes milk production JAK STAT (cytokine receptor) Peptide Stimulates thyroid hormone release GPCR (G proteincoupled receptor) Regulation Amino Acid Molecular Sequence Weight Regulated by hypothalamusreleasing 191 amino hormone acids (GHRH) and inhibited by somatostatin Regulated by hypothalamusreleasing 198 amino hormone (PRH) acids and inhibited by dopamine Regulated by hypothalamus- 118 amino releasing acids hormone (TRH) ~22 kDa ~23 kDa ~28 kDa Pituitary (posterior) Adrenocorticot ropic hormone (ACTH) Peptide Follicle stimulating hormone (FSH) Peptide Luteinizing hormone (LH) Peptide Antidiuretic hormone (ADH) Peptide Oxytocin Peptide Regulated by Stimulates GPCR hypothalamu hormone (melanocortin s-releasing 39 amino acids ~4.5 kDa release by receptor) hormone adrenal cortex (CRH) Regulated by 111 amino acids Stimulates GPCR hypothalamu (alpha subunit) gamete (gonadotropin s-releasing + 89 amino ~30 kDa production receptor) hormone acids (beta (GnRH) subunit) Regulated by 121 amino acids Stimulates GPCR hypothalamu (alpha subunit) androgen (gonadotropin s-releasing + 89 amino ~30 kDa production by receptor) hormone acids (beta gonads (GnRH) subunit) Stimulates Regulated by water V2 receptor osmotic 9 amino acids ~1 kDa reabsorption by (GPCR) changes and kidneys blood volume Stimulates Regulated by uterine Oxytocin uterine contractions receptor stretching 9 amino acids ~1 kDa during (GPCR) and suckling childbirth reflex Thyroid Gland Location and Structure • The thyroid gland is butterfly-shaped and located just inferior to the larynx (voice box). • It consists of right and left lateral lobes connected by an isthmus anterior to the trachea. • Some thyroid glands have a small third lobe called the pyramidal lobe. Thyroid Follicles • Thyroid follicles are microscopic spherical sacs that make up most of the thyroid gland. • The wall of each follicle is composed of follicular cells. • A basement membrane surrounds each follicle. Follicular Cells and Hormones • Follicular cells produce two hormones • Thyroxine (T4), which contains four atoms of iodine. • Triiodothyronine (T3), which contains three atoms of iodine. • T3 and T4 are collectively known as thyroid hormones. • Under the influence of TSH (thyroid-stimulating hormone), follicular cells become active and secrete these hormones. Parafollicular Cells (C Cells) • Parafollicular cells lie between follicles. • They produce calcitonin (CT), which helps regulate calcium homeostasis. Thyroid Gland Thyroid Gland Thyroid Hormones Synthesis Thyroid Hormones Formation, Storage, and Release of Thyroid Hormones 1. Iodide trapping • Thyroid follicular cells trap iodide ions (I−) by actively transporting them from the blood into the cytosol. 2. Synthesis of thyroglobulin • Follicular cells are trapping I−, they are also synthesizing thyroglobulin (TGB), a glycoprotein with two large subunits that is produced in the rough endoplasmic reticulum, modified in the Golgi complex, and packaged into secretory vesicles. • The vesicles then undergo exocytosis, which releases TGB into the lumen of the follicle. 3. Oxidation of iodide • Some of the amino acids in TGB are tyrosine that will become iodinated. • However, negatively charged iodide ions cannot bind to tyrosine until they undergo oxidation to iodine. • As the iodide ions are being oxidized, they pass through the membrane into the lumen of the follicle. 4. Iodination of tyrosine • As iodine atoms (I0) form, they react with tyrosine that are part of thyroglobulin molecules. • Binding of one iodine atom yields mono-iodotyrosine (MIT/T1), and a second iodination produces diiodotyrosine (DIT/T2). • The TGB with attached iodine atoms, a sticky material that accumulates and is stored in the lumen of the thyroid follicle, is termed colloid. • (In total containing approximately 120 tyrosyl residues). 5. Coupling of T1 and T2 • 6. 7. 8. During the last step in the synthesis of thyroid hormone, two T2 molecules join to form T4, or one T1 and one T2 join to form T3. Pinocytosis and digestion of colloid • Droplets of colloid re-enter follicular cells by pinocytosis and merge with lysosomes. • Digestive enzymes in the lysosomes break down TGB, cleaving off molecules of T3 and T4. Secretion of thyroid hormones • Because T3 and T4 are lipid soluble, they diffuse through the plasma membrane into interstitial fluid and then into the blood. (MCT transporter). • T4 normally is secreted in greater quantity than T3, but T3 is several times more potent. • Moreover, after T4 enters a body cell, most of it is converted to T3 by removal of one iodine. Transport in the blood • More than 99% of both the T3 and the T4 combine with transport proteins in the blood, mainly thyroxinebinding globulin (TBG). Formation, Storage, and Release of Thyroid Hormones Formation, Storage, and Release of Thyroid Hormones Na+ and I- enter in follicular cell by NIS symporter I0 Bind to TG-MIT and TG-DIT Lysosomes break down TGB I- enter in colloid from follicular cell by pendrin TG synthesized in follicular cell then enter in colloid by exocytosis Thyroid peroxidase convert I- into I0 Form T3 and T4 Droplets of colloid re-enter follicular cells by pinocytosis Merge with lysosomes Cleaving off molecules of T3 and T4 T3 and T4 diffuse into interstitial fluid and then into the blood by MCT transporter Thyroid Hormones Synthesis Actions of Thyroid Hormones Increase Basal Metabolic Rate (BMR) • Thyroid hormones raise BMR, which is the rate of energy expenditure under standard conditions (awake, at rest, and fasting). • Mechanisms for increased BMR: • Synthesis of additional Na+/K+ ATPases, which use ATP to transport sodium ions (Na+) out of cells and potassium ions (K+) into cells. • Increased enzyme concentrations in cellular respiration, leading to greater breakdown of carbohydrates, lipids, and proteins. • Enhanced activity of mitochondria, resulting in more ATP production. • The sarcoplasmic reticulum Ca++ ATPase is increased by T3. • T3 increases ryanodine Ca++ channels in the sarcoplasmic reticulum. • The calorigenic effect leads to increased heat production and helps maintain normal body temperature. Enhance Actions of Catecholamines • Thyroid hormones up-regulate β-adrenergic receptors. • Catecholamines (epinephrine and norepinephrine) bind to these receptors, promoting sympathetic responses. • Excess thyroid hormone levels can cause increased heart rate, stronger heartbeats, and elevated blood pressure. Actions of Thyroid Hormones Nervous System Development • Thyroid hormones promote • Synapse formation: Enhancing communication between nerve cells. • Myelin production: Supporting nerve cell insulation. • Growth of dendrites: Expanding nerve cell connections. Skeletal System Growth • Thyroid hormones play a role in • Formation of ossification centers in developing bones. • Synthesis of bone proteins. • Secretion of growth hormone (GH) and insulin-like growth factors (IGFs). Consequences of Thyroid Hormone Deficiency • Insufficient thyroid hormones during fetal development, infancy, or childhood lead to • Severe mental retardation. • Stunted bone growth. Regulation of secretion and actions of thyroid hormones TRH = thyrotropin-releasing hormone TSH = thyroidstimulating hormone T3 = triiodothyronine T4 = thyroxine (tetraiodothyronine) Control of Thyroid Hormone Secretion Thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid-stimulating hormone (TSH) from the anterior pituitary stimulate secretion of thyroid hormones. 1. Low blood levels of T3 and T4 or low metabolic rate stimulate the hypothalamus to secrete TRH. 2. TRH enters the hypothalamic–hypophyseal portal system and flows to the anterior pituitary, where it stimulates thyrotrophs to secrete TSH. 3. TSH stimulates virtually all aspects of thyroid follicular cell activity, including iodide trapping, hormone synthesis and secretion, and growth of the follicular cells. 4. The thyroid follicular cells release T3 and T4 into the blood until the metabolic rate returns to normal. 5. An elevated level of T3 inhibits release of TRH and TSH (negative feedback inhibition). 6. Conditions that increase ATP demand; cold environment, hypoglycemia, high altitude, and pregnancy, increase the secretion of the thyroid hormones. Calcitonin • Calcitonin is a hormone produced by the C-cells (also known as parafollicular cells). • Its primary role is to regulate calcium levels in the blood by decreasing them. • Function of Calcitonin • Inhibits Osteoclast Activity • Calcitonin blocks the activity of osteoclasts, which are cells responsible for breaking down bone. • By temporarily inhibiting osteoclasts, calcitonin reduces the release of calcium from bones into the bloodstream. • Kidney Regulation • Calcitonin also decreases the amount of calcium reabsorbed by the kidneys, leading to lower blood calcium levels. • Miacalcin, a calcitonin extract derived from salmon that is 10 times more potent than human calcitonin, is prescribed to treat osteoporosis. • Salmon is the common name for several commercially important species of euryhaline ray-finned fish from the genera Salmo and Oncorhynchus of the family Salmonidae. Summary Parathyroid Glands Location and Structure • Parathyroid glands are partially embedded in the posterior surface of the lateral lobes of the thyroid gland. • Each parathyroid gland has a mass of about 40 mg (0.04 g). • Typically, there is one superior and one inferior parathyroid gland attached to each lateral thyroid lobe. Microscopic Composition • Parathyroid glands contain two types of epithelial cells: • Chief cells (Principal cells): These cells produce parathyroid hormone (PTH). • Oxyphil cells: Their function is not fully understood in normal parathyroid glands, but they aid in histological identification due to unique staining characteristics. • In parathyroid cancer, oxyphil cells may secrete excess PTH. Parathyroid Glands Parathyroid Glands Parathyroid Hormone Regulation of Blood Ions • PTH regulates calcium (Ca²⁺), magnesium (Mg²⁺), and phosphate (HPO₄²⁻) levels in the blood. • It increases the number and activity of osteoclasts, leading to bone resorption. • This releases Ca²⁺ and HPO₄²⁻ into the bloodstream. Kidney Actions • PTH acts on the kidneys • Slows the loss of Ca²⁺ and Mg²⁺ from blood into urine. • Increases the loss of HPO₄²⁻ from blood into urine. • Overall, this decreases blood HPO₄²⁻ levels and increases Ca²⁺ and Mg²⁺ levels. Calcitriol Formation • PTH promotes the formation of calcitriol (active vitamin D). • Calcitriol enhances absorption of Ca²⁺, HPO₄²⁻, and Mg²⁺ from the gastrointestinal tract into the blood. Control of Secretion of Calcitonin and Parathyroid Hormone Control of Secretion of Calcitonin and Parathyroid Hormone The blood calcium level directly controls the secretion of both calcitonin and parathyroid hormone via negative feedback loops that do not involve the pituitary gland. 1. A higher-than-normal level of calcium ions (Ca2+) in the blood stimulates parafollicular cells of the thyroid gland to release more calcitonin. 2. Calcitonin inhibits the activity of osteoclasts, thereby decreasing the blood Ca2+ level. 3. A lower-than-normal level of Ca2+ in the blood stimulates chief cells of the parathyroid gland to release more PTH. 4. PTH promotes resorption of bone extracellular matrix, which releases Ca2+ into the blood and slows loss of Ca2+ in the urine, raising the blood level of Ca2+. 5. PTH also stimulates the kidneys to synthesize calcitriol, the active form of vitamin D. 6. Calcitriol stimulates increased absorption of Ca2+ from foods in the gastrointestinal tract, which helps increase the blood level of Ca2+. Summary CSIR NET practice problem Q. Which of the following is a hormone as well as a neurotransmitter? (June 2001) (a) Adrenaline (b) Acetylcholine (c) Thyroxine (d) Glucagon Answer; a CSIR NET practice problem Q. Which hormone is secreted by both, hypothalamus and intestinal tract? (June 2002) (a) Somatostatin (b) Epinephrine (c) Vasopressin (d) Secretin Answer; a CSIR NET practice problem Q. Hormone which controls the amount of water reabsorbed from the collecting ducts and tubules in the kidney is (Dec 2004) (a) ACTH (b) Insulin (c) Antidiuretic hormone (ADH) (d) Oxytocin Answer; c CSIR NET practice problem Q. Insulin dependent glucose uptake by muscles and adipose tissue is mediate by (Dec 2004) (a) Endocytosis (b) Pinocytosis (c) Phagocytosis (d) Facilitated diffusion Answer; d CSIR NET practice problem Q. Endocrine signaling is analogous to- (June 2005) (a) Making a telephone call (b) Radio transmission (c) Talking to self (d) Talking to partner over walky-talky Answer; b CSIR NET practice problem Q. Which statement is FALSE about animal hormones? (Dec 2005) (a) They are secreted by many specialized cells. (b) They can influence through humoral route. (c) They can bind to more than one type of receptors. (d) They are required in large amount to elicit their response Answer; d CSIR NET practice problem Q. The mechanism of action of steroid hormone is (Dec 2006) (a) Binding to membrane receptor and activating secondary messenger. (b) Binding to nuclear receptor and hormone-receptor complex activates target gene expression. (c) Hormone moves to nucleus and starts transcription. (d) Hormone mainly target protein synthesis. Answer; b CSIR NET practice problem Q. Among the following which is smallest hypothalamic neuro-peptide hormone? (June 2007) (a) GnRH (b) CRH (c) TRH (d) GH-RH Answer; c CSIR NET practice problem Q. Which one of the following is responsible for the ejection of milk from mammary glands in mammals? (Dec 2012) (a) Oxytocin (b) Prolactin (c) Serotonin (d) Melatonin Answer; a CSIR NET practice problem Q. Vasopressin secretion does NOT increase with (Dec 2016) (a) Exercise (b) An increase in extracellular fluid volume (c) Standing (d) Vomiting Answer; b CSIR NET practice problem Q. Mammillary bodies are present in (Dec 2017) (a) Thalamus (b) Epithalamus (c) Hypothalamus (d) Midbrain Answer; c CSIR NET practice problem Q. Hypophysiotropic hormones are secreted into blood at (Dec 2019) (a) Posterior lobe of pituitary (b) Median eminence (c) Mammillary bodies (d) Anterior lobe of pituitary Answer; b CSIR NET practice problem Q. Certain statements made on the mechanisms of action of a neuro-hormone, vasopressin (VP) are given below: (Dec 2019) A. VP acts on collecting ducts of kidney to concentrate urine by binding to V2 receptors and activating CAMP cascade. B. VP acts on collecting ducts of kidney to concentrate urine by binding to V2 receptors and activating CAMP cascade. C. VP acts on blood vessels to produce constriction by binding to V2 receptors and activating CAMP cascade. D. VP acts on blood vessels to produce constriction by binding to V2 receptors and activating phosphatidylinositol cascade. Which one of the following options represents a combination of correct statements? (a) A and B (b) C and D (c) B and D (d) A and D Answer; C CSIR NET practice problem Q. Given below are some statements about pituitary hormones: (Sep 2022) A. Oxytocin and vasopressin are synthesized in posterior pituitary. B. Prolactin is synthesized from anterior pituitary. C. α and β MSH are secreted from intermediate lobe of pituitary in adult humans. D. Growth hormone secretion from anterior pituitary is stimulated by hyperglycemia. E. Prolactin secretion is markedly increased by sleep. Choose the INCORRECT combination of statements from below: (a) A, C and D (b) A, B and D (c) C, D and E (d) B, C and E Answer; a CSIR NET practice problem Q. Prolactin is an anterior pituitary hormone which is lactogenic and helps milk production in mammals. The statements below are made regarding the mechanism of action of prolactin: (June 2023) A. The receptors that bind to prolactin lack intrinsic tyrosine kinase activity. B. Upon prolactin binding, the receptors dimerize, and associated kinase is activated. C. Prolactin binding to receptors leads to activation of its intrinsic kinase activity. D. STAT plays a role in mediating prolactin action. It dimerizes after its phosphorylation to elicit the response. E. There is no involvement of STAT in prolactin action mechanisms. Which one of the following options represents the combination of all correct statements? (a) A, B and D (b) B, C and D (c) A and E only (d) A, E, D Answer; a CSIR NET practice problem Q. Which one of the following amino acids is present in vasopressin at position 3? (Dec 2023) (a) Tyrosine (b) Phenylalanine (c) Glutamine (d) Asparagine Answer; b CSIR NET practice problem Q. Which one of the following is used in organification of tyrosine residues in thyroglobulin protein, during thyroid hormone biosynthesis? (a) Iodine (b) Reduced iodine (c) Oxidized iodine (d) Hydrogen iodide Answer; c CSIR NET practice problem Q. What would be effect on serum concentration of TSH if thyroxine is injected to a person? (Dec 2010) (a) Remain unchanged. (b) First increase and then come to normal. (c) Initially decrease but after short time will be normal. (d) Remain high for prolonged period of time. Answer; c CSIR NET practice problem Q. Thyroid hormone (T3) increases the heart rate and the force of contraction of cardiac muscles. The mechanisms of these effects of T3 have been explained by a researcher in the following statements: (Dec 2019) A. T3 inhibits the expression of gene for α-myosin heavy chain gene for β-myosin heavy chain. and enhances the expression B. The expression of gene for Na+-Ca++ antiporter is enhanced by T3. C. The sarcoplasmic reticulum Ca++ ATPase is increased by T3. D. T3 increases ryanodine Ca++ channels in the sarcoplasmic reticulum. E. The number of β-adrenergic receptors in heart muscles is inhibited by T3. Which one of the following combinations contains both correct explanations? (a) A and B (b) B and C (c) C and D (d) D and E Answer; c of CSIR NET practice problem Q. Synthesis of thyroid hormones (T3 and T4) takes place in a highly intricate manner in the thyroid gland. Following statements are made regarding synthesis of these hormones. (Dec 2023) A. Iodine enters the thyroid follicular cells through a transporter. B. Thyroid hormone synthesis takes place outside the follicular cells in the follicular colloid. C. Thyroglobulin glycoprotein is composed of four large subunits. D. Thyroglobulin glycoprotein is composed of two large subunits. Which one of the following options has the combination of correct statements? a. A and C b. B and D c. B and C d. A and D Answer; b Your future is created by what you do today, not tomorrow