Hypothalamic Regulation of Hormonal Function PDF

Chapter 17 Hypothalamic Regulation of Hormonal Function BY Dr. Basman Qasim Many of the complex autonomic mechanisms that maintain the chemical constancy and temperature of the internal Introduction...

Chapter 17 Hypothalamic Regulation of Hormonal Function BY Dr. Basman Qasim Many of the complex autonomic mechanisms that maintain the chemical constancy and temperature of the internal Introduction environment are integrated in the hypothalamus. The Hypothalamus also functions with the limbic system as a unit that regulates Emotional and instinctual behavior Relation to the Pituitary Gland The pituitary gland, often called the "master gland," has a unique connection to the hypothalamus, which regulates many of its functions. Structurally, the pituitary gland is divided into two main parts: the anterior and posterior lobes, which differ in origin, structure, and function. The posterior pituitary, or neurohypophysis, develops embryologically as an extension of the hypothalamus itself, forming from the floor of the third ventricle. This lobe is primarily composed of axon terminals from the hypothalamic neurons located in the supraoptic and paraventricular nuclei. These neurons send their axons down the hypothalamohypophysial tract to release hormones directly into the bloodstream from the posterior lobe. The supraoptic nucleus predominantly sends its fibers to the posterior pituitary, while some fibers from the paraventricular nucleus project to the median eminence. The hormones released from the posterior pituitary—oxytocin and vasopressin (antidiuretic hormone, ADH)—are produced in the hypothalamus and travel down these axons to be stored and released as needed. In contrast, the anterior pituitary, or adenohypophysis, arises embryologically from the Rathke’s pouch, which is an invagination of the oral cavity's roof, or pharynx. This part of the pituitary is connected to the hypothalamus via a vascular network rather than direct neural connections. The hypothalamus releases regulatory hormones into this vascular system, specifically the hypophyseal portal system -that is arise from the median eminence- which carries these hormones to the anterior pituitary. There, they stimulate or inhibit the secretion of key hormones like growth hormone, prolactin, ACTH, TSH, FSH, and LH. This indirect connection allows the hypothalamus to exert control over various endocrine functions of the anterior pituitary without direct nerve fibers. The anterior pituitary relies heavily on a specialized blood supply that links it directly to the hypothalamus. This link, called the hypophyseal portal system, allows the hypothalamus to control hormone release from the anterior pituitary without direct nerve connections. 1.Portal Hypophyseal Vessels: Instead of being directly connected by nerves, the hypothalamus communicates with the anterior pituitary through blood vessels called the portal hypophyseal vessels. These vessels carry small amounts of releasing and inhibiting hormones from the hypothalamus down to the anterior pituitary. 2.Primary Capillary Plexus: The hypothalamus has a network of capillaries—called the primary plexus—that forms at its base from arteries near the brain (the carotid arteries and Circle of Willis). This plexus is full of small, permeable blood vessels that allow hormones from the hypothalamus to enter the bloodstream quickly. 3.Direct Vascular Pathway: The blood in this system flows from the hypothalamus to the anterior pituitary without first going to the heart. This allows rapid and direct hormone transfer and makes it a true "portal system." 4.Median Eminence: This area, at the base of the hypothalamus, is where the portal vessels start. Because it’s outside the blood-brain barrier, it can quickly release hypothalamic hormones into the portal system. This setup ensures that hypothalamic hormones reach the anterior pituitary in a highly efficient, direct way, helping regulate vital functions like growth, metabolism, and reproduction. Figure (17-1) Thirst is regulated by multiple systems in the body to ensure proper hydration and electrolyte balance. Thirst Mechanisms of Thirst 3. Additional Thirst Triggers: 1.Osmolality-Related Thirst: When plasma osmolality (the 1. Baroreceptors: Sensors in the heart and concentration of solutes in blood) increases which is associated blood vessels that detect changes in dehydration or high salt intake, the brain senses it, triggering thirst to blood pressure also help trigger thirst help dilute the blood and restore balance. in response to low blood volume. 2. Prandial Drinking: People often drink 2.Blood Volume-Related Thirst: When there’s a drop in extracellular more during meals, a response likely fluid (ECF) volume, like during bleeding (hemorrhage), thirst is also due to a combination of increased triggered, even if plasma osmolality hasn’t changed. This is managed osmolality from absorbed food and through the renin-angiotensin system: hypovolemia (low blood signals from gastrointestinal volume) causes kidneys to release renin, which leads to increased hormones. angiotensin II—a hormone that stimulates thirst centers in the brain, particularly in the subfornical organ and possibly the organum vasculosum of the lamina terminalis OVLT. These brain areas are 3. Damage to brain areas involved in thirst unique in being outside the blood-brain barrier, so they can quickly regulation, such as from hypothalamic injury or detect and respond to blood changes. Figure (17-4) certain psychiatric conditions, can impair the sensation of thirst. This can lead to dehydration Note: drugs that block the action of angiotensin II do not completely or hypernatremia (high blood sodium levels) if block the thirst response to hypovolemia. water intake isn’t adequately maintained. Control of posterior pituitary secretions vasopressin & oxytocin The posterior pituitary releases two main hormones, vasopressin (AVP) and oxytocin, which are small peptides with a stabilizing disulfide ring. Vasopressin regulates water balance by promoting kidney water reabsorption, while oxytocin triggers uterine contractions and milk release. In most mammals, vasopressin contains arginine, but in some species, like hippopotami and pigs, lysine replaces arginine, forming lysine vasopressin. Both hormones are produced in the hypothalamus and stored in the posterior pituitary for release. BIOSYNTHESIS, INTRANEURONAL TRANSPORT, & SECRETION The posterior pituitary hormones, oxytocin and vasopressin, are produced in the cell bodies of large neurons (magnocellular neurons) located in the hypothalamus, specifically in the supraoptic and paraventricular nuclei. Once synthesized, these hormones are transported along the neurons’ axons to their terminals in the posterior pituitary. Here, they are stored and released into the bloodstream in response to electrical signals. These hormones are classified as neural hormones since they are produced by nerve cells and released directly into circulation. Vasopressin & oxytocin in other locations Beyond their primary roles in the hypothalamus and posterior pituitary, vasopressin and oxytocin are found in other parts of the body, suggesting additional, less-understood functions: 1.Vasopressin in the Suprachiasmatic Nucleus: Vasopressin-secreting neurons are present in the suprachiasmatic nucleus (SCN), the brain’s primary circadian clock, hinting at a role for vasopressin in regulating daily physiological rhythms. 2.Cardiovascular Control: Both vasopressin and oxytocin are found in neurons projecting from the paraventricular nucleus to the brainstem and spinal cord, where they may help regulate blood pressure and other aspects of cardiovascular function. 3.Synthesis in Other Organs: Vasopressin and oxytocin are also produced in gonads, adrenal cortex, and thymus. While the exact functions of these hormones in these organs remain unclear, they may play roles in local tissue signaling or developmental processes unique to each organ. Vasopressin Receptors There are at least three kinds of vasopressin receptors: V1A, V1B, and V2. All are G-protein–coupled. The V1A and V1B receptors act through phosphatidylinositol Hydrolysis to increase intracellular Ca2+ concentrations. The V2 receptors act through Gs to increase cyclic adenosine monophosphate levels. Effects of Vasopressin Because one of its principal physiologic effects is the retention of water by the kidney, vasopressin is often called the antidiuretic hormone (ADH). It increases the permeability of the collecting ducts of the kidney so that water enters the hypertonic interstitium of the renal pyramids (Chapter 37). The urine becomes concentrated and its volume decreases. The overall effect is therefore retention of water in excess of solute; consequently, the effective osmotic pressure of the body fluids is decreased. In the absence of vasopressin,1) the urine is hypotonic to plasma,2) urine volume is increased, and there is a net water loss. Consequently, 3) the osmolality of the body fluid rises Effects of Oxytocin In humans, oxytocin acts primarily on the breasts and uterus, though it appears to be Involved in luteolysis as well. A G-protein–coupled oxytocin receptor has been Identified in human myometrium, and a similar or identical receptor is found in Mammary tissue and the ovary. It triggers increases in intracellular Ca2+ levels. Anterior Pituitary Hormones The anterior pituitary secretes six hormones: adrenocorticotropic hormone (corticotropin, ACTH), thyroid-stimulating hormone (thyrotropin, TSH), growth Hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and Prolactin (PRL). An additional polypeptide, β-lipotropin (β-LPH), is secreted with ACTH, but its physiologic role is unknown Nature of Hypothalamic Control Anterior pituitary secretion is controlled by chemical agents carried in the portal Hypophysial vessels from the hypothalamus to the pituitary. These substances used to be called releasing and inhibiting factors, but now they are commonly called Hypophysiotropic hormones. The latter term seems appropriate since they are secreted into the bloodstream and act at a distance from their site of origin. Small amounts escape into the general circulation, but they are at their highest concentration in portal hypophysial blood. Hypophysiotropic Hormones There are six established hypothalamic releasing and inhibiting hormones (Figure17–10): corticotropin-releasing hormone (CRH); thyrotropin-releasing hormone (TRH); growth hormone– releasing hormone (GRH); growth hormone–inhibiting Hormone (GIH, now generally called somatostatin); luteinizing hormone–releasing Hormone (LHRH, now generally known as gonadotropin-releasing hormone [GnRH]); and prolactin-inhibiting hormone (PIH). In addition, hypothalamic Extracts contain prolactin-releasing activity, and a prolactin-releasing hormone(PRH) has been postulated to exist. TRH, VIP, and several other receptors for most of the hypophysiotropic hormones are coupled to G-proteins. In humans, there are two receptors for corticotropin-releasing hormone (CRH): hCRH-RI and hCRH-RII. While hCRH-RI has a clear role in stimulating ACTH release, the function of hCRH-RII remains unclear, though it is present in various brain areas. Additionally, a CRH-binding protein is found in the peripheral blood and within corticotrope cells in the anterior pituitary. This protein may inactivate CRH in circulation and might help internalize CRH receptors in corticotropes, though its precise physiological role is unknown. Unlike CRH, other hormones that control pituitary functions( hypophysiotropic ) don’t have known binding proteins.