Hypothalamus-Pituitary-Adrenal Axis PDF

Hypothalamus –pituitary- adrenal gland axis HPA  The HPA axis is a major neuroendocrine system that controls reactions to stress Stress, generally defined as any stimulus that disrupts the body’s internal balance (i.e., physiological homeostasis) The HPA stress...

Hypothalamus –pituitary- adrenal gland axis HPA  The HPA axis is a major neuroendocrine system that controls reactions to stress Stress, generally defined as any stimulus that disrupts the body’s internal balance (i.e., physiological homeostasis) The HPA stress response is driven primarily by corticotrophin releasing hormone (CRH) release from hypothalamic paraventricular nucleus (PVN). the HPA axis mobilizes energy reserves to insure that the organism has the resources needed to meet stress  The paraventricular nucleus of the hypothalamus synthesize and secrete corticotropin-releasing hormone (CRH). CRH is transported to the anterior pituitary through the portal blood vessel system of the hypophyseal stalk stimulate the secretion of stored ACTH from corticotrope cells ACTH is transported by the blood to the adrenal cortex of the adrenal gland  CRH CRH is a 41-amino-acid peptide hormone CRH binds to G protein-coupled receptors on the corticotropic cell membrane and stimulates cAMP production Corticotrophs are the cells in the anterior pituitary that produce prohormone “pro-opiomelanocortin” (POMC) which undergoes cleavage to release adrenocorticotropic hormone (ACTH), also melanocyte-stimulating hormone (MSH),  Adrenocorticotropic hormone (ACTH) ACTH, a 39 amino acid peptide hormone ACTH stimulates secretion of glucocorticoid steroid hormones and androgen from adrenal cortex cells ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a G protein–coupled receptor by activating adenylyl cyclase which increase intracellular cAMP and subsequent activation of protein kinase A.  Action ACTH stimulate cholesterol delivery by steroidogenic acute regulatory (StAR) protein into the mitochondria where the P450scc enzyme is located. P450scc catalyzes the first step of steroidogenesis. ACTH also stimulates lipoprotein uptake into cortical cells. This increases the bioavailability of cholesterol in the cells of the adrenal cortex. ACTH also stimulate the transcription of the genes coding for steroidogenic enzymes, especially P450scc Adrenal gland  A small gland that makes steroid hormones, adrenaline, and noradrenaline. These hormones help control heart rate, blood pressure, and other important body functions. There are two adrenal glands, one on top of each kidney. Also called suprarenal gland  Anatomy The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: -zona glomerulosa: mineralocorticoids steroid H -zona fasciculate: glucocorticoids steroid H (stress H) -zona reticularis: androgen steroid H adrenal medulla is located in the center of an adrenal gland. The adrenal gland is enveloped by a protective layer of adipose capsule  HPA feedback system is mediated via the circulating level of plasma cortisol in negative feedback on CRH and ACTH Disorders  Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to cortisol Cushing's syndrome refers to excess cortisol of any etiology Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat swelling between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly Women may have more hair and irregular menstruation Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness  caused by either excessive cortisol-like medication or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands Cases due to a pituitary adenoma are known as Cushing's disease A 24-hour free cortisol level greater than 100 micrograms is diagnostic of Cushing's syndrome  Cushing's disease Cases due to a pituitary adenoma excess production of ACTH from a corticotroph cells or due to excess production of hypothalamus CRH Exogenous steroid administration Symptoms of glucocorticoid excess generally occur with the administration of oral steroids; however, occasionally injections of steroids into joints and the use of steroid inhalers can cause Cushing syndrome.  Adrenal Insufficiency (Addison's Disease) The problem may be due to a disorder of the adrenal glands themselves (primary adrenal insufficiency) or to inadequate secretion of ACTH by the pituitary gland (secondary adrenal insufficiency). The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and non-exposed parts of the body.  About 70 percent of reported cases of Addisons disease are due to autoimmune disorder causing the gradual destruction of the adrenal cortex  Etiology of adrenal insufficiency: Primary: autoimmune processes (50 – 65 %); tuberculosis; neoplasm, metastatic carcinoma; inflammatory necrosis; amyloidosis; heamochromatosis; bilateral adrenal hemorrhage or infarction, intra – adrenal hemorrhage bilateral adrenalectomy; Secondary: hypothalamic or pituitary disease (primary injury of these organs leads to insufficiency of ACTH secretion that cause the two – side atrophy of adrenal glands); glucocorticoid therapy.  PHEOCHROMOCYTOMA. It is a tumor of chromaffin cells that secrete catecholamines  Symptoms Signs and symptoms of pheochromocytomas often include: High blood pressure Heavy sweating Headache Rapid heartbeat (tachycardia) Tremors Paleness in the face Shortness of breath (dyspnea)