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Mechanisms of Hormonal Regulation
- The endocrine system and diverse functions, including sexual differentiation, growth and development, and continuous maintenance of the body’s internal environment.
- Hormones are chemical messengers synthesized by endocrine glands and released into the circulation.
- Hormones have specific negative and positive feedback mechanisms. Most hormone levels are regulated by negative feedback, in which hormone secretion raises the level of a specific hormone, ultimately causing secretion to subside.
- Endocrine feedback is described in terms of short, long, and ultra-short feedback loops.
- Water-soluble hormones circulate throughout the body in unbound form, whereas lipid-soluble hormones (i.e., steroid and thyroid hormones) circulate throughout the body bound to carrier proteins.
- Hormones affect only target cells with appropriate receptors and then act on these cells to initiate specific cell functions or activities.
- Hormones have two general types of effects on cells: (a) direct effects, or obvious changes in cell function, and (b) permissive effects, or less obvious changes that facilitate cell function.
- Receptors for hormones may be located on the plasma membrane or in the intracellular compartment of a target cell.
- Water-soluble hormones act as first messengers, binding to receptors on the cell’s plasma membrane. The signals initiated by hormone-receptor binding are then transmitted into the cell by the action of second messengers.
- Lipid-soluble hormones (including steroid and thyroid hormones) cross the plasma membrane by diffusion. These hormones diffuse directly into the cell nucleus and bind to nuclear receptors. Rapid responses of steroid hormones may be mediated by plasma membrane receptors.
Structure and Function of the Endocrine Glands
- The pituitary gland, consisting of anterior and posterior portions, is connected to the central nervous system through the hypothalamus.
- The hypothalamus regulates anterior pituitary function by secreting releasing hormones and releasing factors into the portal circulation.
- Hypothalamic hormones include prolactin-inhibiting factor (PIF), which inhibits prolactin secretion; thyrotropin-releasing hormone (TRH), which affects release of thyroid hormones; gonadotropin-releasing hormone (GnRH), which facilitates release of adrenocorticotropic hormone (ACTH) and endorphins; and substance P, which inhibits ACTH release and stimulates release of a variety of other hormones.
- The posterior pituitary secretes antidiuretic hormone (ADH), which also is called vasopressin, and oxytocin.
- Hormones of the anterior pituitary are regulated by: (a) secretion of hypothalamic-releasing hormones or factors, (b) negative feedback from hormones secreted by target organs, and (c) mediating effects of neurotransmitters.
- Hormones of the anterior pituitary include ACTH, melanocyte-stimulating hormone (MSH), somatotropic hormones (growth hormone [GH] prolactin, and glycoprotein hormones – follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH).
- ADH controls serum osmolality, increases permeability of the renal tubules to water, and causes vasoconstriction when administered pharmacologically in high doses. ADH also may regulate some central nervous system functions.
- Oxytocin causes uterine contraction and lactation in women and may have a role in sperm motility in men. In both men and women, oxytocin has an antidiuretic effect similar to that of ADH.
- The two-lobed thyroid gland contains follicles, which secrete some of the thyroid hormones, and C cells, which secrete calcitonin and somatostatin.
- Regulation of thyroid hormone (TH) levels is complex and involves the hypothalamus, anterior pituitary, thyroid gland, and numerous biochemical variables.
- Thyroid hormone (TH) secretion is regulated by thyroid-releasing hormone (TRH) through a negative feedback loop that involves the anterior pituitary and hypothalamus.
- Thyroid-stimulating hormone (TSH), which is synthesized and stored in the anterior pituitary, stimulates secretion of TH by activating intracellular processes, including uptake of iodine necessary for the synthesis of TH.
- Once secreted, TH acts the thyroid gland, the anterior pituitary, and the median eminence to regulate further TH production.
- Synthesis of TH depends on the glycoprotein thyroglobulin (TG), which contains a precursor of TH, tyrosine. Tyrosine then combines with iodine to form precursor molecules of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).
- When released into the circulation, T3 and T4 are bound by carrier proteins in the plasma, which store these hormones and provide a buffer for rapid changes in hormone levels. The free form is the active form.
- Thyroid hormones alter protein synthesis and have a wide range of metabolic effects on proteins, carbohydrates, lipids, and vitamins. TH also affects heat production and cardiac function.
- The paired parathyroid glands normally are located behind the upper and lower poles of the thyroid. These glands secrete parathyroid hormone (PTH), an important regulator of serum calcium levels.
- PTH secretion is regulated by levels of ionized calcium in the plasma and by cyclic adenosine monophosphate (cAMP) within the cell.
- In bone, PTH causes bone breakdown and resorption, in the kidney, PTH increases reabsorption of calcium and decreases reabsorption of phosphorus and bicarbonate.
- The endocrine pancreas contains the islets of Langerhans, which secrete hormones responsible for much of the carbohydrate metabolism in the body.
- The islets of Langerhans consist of alpha cells, beta cells, delta cells, and F cells.
- Alpha cells produce glucagon, which is secreted inversely to blood glucose concentrations.
- Delta cells secrete somatostatin, which inhibits glucagon and insulin secretion.
- Beta cells secrete preproinsulin, which is ultimately converted to insulin.
- F cells secrete pancreatic polypeptide.
- Insulin is a hormone that regulates blood glucose concentrations and overall body metabolism of fat, protein, and carbohydrates.
- The paired adrenal glands are situated above the kidneys. Each gland consists of an adrenal medulla, which secretes catecholamines, and an adrenal cortex, which secretes steroid hormones.
- The steroid hormones secreted by the adrenal cortex are synthesized from cholesterol. These hormones include glucocorticoids, Mineralocorticoids, and adrenal androgens and estrogens.
- Glucocorticoids directly affect carbohydrate metabolism by increasing blood glucose concentration through gluconeogenesis in the liver and be decreasing use of glucose. Glucocorticoids inhibit immune and inflammatory responses.
- The most potent naturally occurring glucocorticoids is cortisol, which is necessary for the maintenance of life and for protection from stress. Secretion of cortisol is regulated by the hypothalamus and anterior pituitary.
- Cortisol secretion is related to secretion of adrenocorticotropic hormone (ACTH), which is stimulated by corticotrophin-releasing hormone (CRH). ACTH binds with receptors of the adrenal cortex, which activates intracellular mechanisms (specifically cyclic AMP) and leads to cortisol release.
- Mineralocorticoids are steroid hormones that directly affect ion transport by renal tubular epithelial cells, causing sodium retention and potassium and hydrogen loss.
- Aldosterone is the most potent of the naturally occurring Mineralocorticoids. Its primary roles is to conserve sodium.
- Aldosterone secretion is regulated primarily by the renin-angiotensin system and serum sodium concentration.
- Aldosterone acts by binding to a site on the cell nucleus and altering protein production within the cell. Its principal site of action is the kidney, where it causes sodium reabsorption and potassium and hydrogen excretion.
- Androgens and estrogens secreted by the adrenal cortex act in the same way as those secreted by the gonads.
- The adrenal medulla secretes the catecholamines epinephrine and norepinephrine. Epinephrine is 10 times more potent than norepinephrine in exerting metabolic effects. Their release is stimulated by sympathetic nervous system stimulation, ACTH, and glucocorticoids.
- Catecholamines bind with carious target cells and are taken up by neurons or excreted in the urine. They cause a range of metabolic effects characterizes as the fight-or-flight response and include hyperglycemia and immune suppression.
- The endocrine system acts together with the nervous system to respond to stressors.
- The response to stressor involves (a) activation of the sympathetic division of the autonomic nervous system and (b) activation of the endocrine system.
- Other hormones that are secreted in response to stress include growth hormone (GH), prolactin, testosterone, antidiuretic hormone (ADH), and insulin.
- The adrenal glands and the sympathetic neurons that innervate these glands form the sympathoadrenal axis.
Aging & Its Effects on Specific Endocrine Glands
The general changes in the endocrine glands that occur with older age include atrophy and weight loss with vascular changes, decreased secretion, and clearance of hormones, and variable change in receptor binding and intracellular responses.