Endocrine System

Type I Diabetes - % diabetics - Age of onset - Pathogenesis - Plasma insulin - Family history - Obesity

- 10% - Usually < 30 years - Presence of islet cell antibodies, Autoimmune, decreased insulin secretion - Usually none - Usually none - Uncommmon

Type II Diabetes - % diabetics - Age of onset - Pathogenesis - Plasma insulin - Family history - Obesity

- 90% - Usually > 30 years - Resistance to insulin, Increased hepatic glucose production - Low, normal, or high; Etiology dependent - Strong - Common

Thyroid hormones characteristics

- T3 is five times more potent than T4 - T4 and T3 are transported via plasma proteins. Approximately 99.5% of these hormones are bound to proteins, but only an unbound hormone is able to enter a cell and elicit a cellular response - All of the T4 in the body is formed and secreted by the thyroid gland; however, only 20% of T3 is produced by the thyroid gland. - The majority of T3 is produced by the conversion of T4 to T3 by the enzyme 5'-monodeiodase, found primarily in the peripheral tissues.

EPO causes...

- stimulation of the stem cells to differentiate into rubrilblasts (least mature erythrocytes) - increased rate of mitosis - increased release of reticulocytes from the bone marrow - increased hemoglobin (HgB) formation, which results in the critical HgB concentration necessary for RBC maturity to be reached at a more rapid rate.

Antidiuretic Hormone (ADH: vasopressin)

ADH increases the permeability of the nephron's collecting duct to water, thereby promoting water reabsorption and increasing blood volume, which subsequently increases blood pressure. ADH is secreted when plasma osmolarity increases, as sensed by osmoreceptors in the hypothalamus, or when blood volume decreases, as sensed by baroreceptors in the circulatory system.

Calcitonin

Calcitonin decreases plasma Ca concentration by inhibiting the release of Ca from bone. Calcitonin secretion is regulated by plasma Ca levels. Calcitonin is antagonistic to parathyroid hormone.

Glucagon

Glucagon stimulates protein and fat degradation, the conversion of glycogen to glucose, and gluconeogenesis, all of which serve to increase blood glucose levels. Glucagon's actions are largely antagonistic to those of insulin.

Glucocorticoids

Glucocorticoids, such as cortisol and cortisone, are involved in glucose regulation and protein metabolism. Glucocorticoids raise blood glucose levels by promoting protein breakdown and gluconeogenesis and decreasing protein synthesis. Glucocorticoids increase plasma glucose levels and are antagonistic to the effects of insulin. Glucocorticoids release amino acids from skeletal muscle as well as lipids from adipose tissue. They also promote the peripheral use of lipids and have anti-inflammatory effects.

Mechanism of Hormone Action

Hormones are classified on the basis of their chemical structure into two major groups: peptide hormones and steroid hormones. There are two ways in which hormones affect the activities of their target cells: via extracellular receptors or intracellular receptors

Interactions with the anterior pituitary

Hypothalamic releasing hormones stimulate or inhibit the secretions of the anterior pituitary. For example, GnRH stimulates the anterior pituitary to secrete FSH and LH. Releasing hormones are secreted into the hypothalamic-hypophyseal portal system. In this circulatory pathway, blood from the capillary bed in the hypothalamus flows through a portal vein into the anterior pituitary, where it diverges into a second capillary network. In this way, releasing hormones can immediately reach the anterior pituitary. A complicated feedback system regulates the secretions of the endocrine system. For example, when the plasma levels of adrenal cortical hormones drop, hypothalamic (via a negative feedback mechanism) release corticotropin-releasing factor (CRF) into the portal system, which signals the pituitary cells to release ACTH. ACTH then acts on the adrenal cortex to increase glucocorticoid levels. When the plasma concentration of corticosteroids exceeds the normal plasma level, the steroids themselves exert an inhibitory effect on the hypothalamus.

How is hyperthyroidism treated?

Hypothyroidism is often treated with supplementation of thyroid hormones via synthetic or animal derived products. Hyperthyroidism can be treated by antithyroid medications that suppress the thyroid's release of excess hormone or ablation of the thyroid with radiation. After ablation, the thyroid no longer produces thyroid hormone, and the patient must take thyroid supplementation for the rest of his or her life.

Cortical sex hormone

In both men and women, the adrenal cortex secretes small quantities of androgen (male sex hormone) like androstenedione and dehydroepinandrosterone. In men, most of the androgens are produced by the testes, so the physiologic effect of the adrenal androgens is quite small. In women, however, overpopulation of the adrenal androgens may have masculinizing effects, such as excessive facial hair.

Hyperthyroidism

In hypothyroidism, thyroid hormones are undersecreted or not secreted at all. Common symptoms of hypothyroidism include a slowed heart rate and respiratory rate, fatigue, cold intolerance, and weight gain. Hypothyroidism in newborn infants, called cretinism, is characterized by mental retardation and short stature. In hyperthyroidism, the thyroid is overstimulated, resulting in the oversecretion of thyroid hormones. Symptoms often include increased metabolic rate, feelings of excessive warmth, profuse sweating, palpitations, weight loss, and protruding eyes. In both disorders the thyroid often enlarges, forming a bulge in the neck called a goiter.

Adrenal Cortex

In response to stress, adrenocorticotropic hormone (ACTH), which is produced by the anterior pituitary, stimulates the adrenal cortex to produce more than two dozen different steroid hormones, collectively known as adrenocortical steroids, or simply corticosteroids. In the bloodstream, these corticosteroids are bound to transport proteins called transcortins. Corticosteroids exert their action by determining which genes are transcribed in the nuclei of their target cells and at what rate. The subsequent changes in the nature and concentration of the proteins produced in the target cells will affect metabolism and other cellular functions. The three major classes are glucocorticoids, mineralocorticoids, and cortical sex hormones.

Gastrointestinal Hormones

Ingested food stimulates the stomach to release the hormone gastrin. Gastrin is carried to the gastric glands and stimulates the glands to secrete HCL in response to food in the stomach. Secretion of pancreatic juice, the exocrine product of the pancreas, is also under hormonal control. The hormonse secretin is released by the small intestine when acidic chyme enters from the stomach. Secretin stimulates the secretion of an alkaline bicarbonate solution from the pancreas that neutralizes the acidity of the chyme. The hormone cholecystokinin is released by the small intestine in response to the presence of fats and causes the contraction of the gallbladder and release of bile into the small intestine. Bile, which is not a hormone, is involved in the emulsification and digestion of fats.

Insulin

Insulin is a protein hormone secreted in response to a high blood glucose concentration. It stimulates the uptake of glucose by muscle and adipose cells and the storage of glucose by muscle and adipose cells and the storage of glucose as glycogen in muscle and liver cells, thus lowering blood glucose levels. It also stimulates the synthesis of fates from glucose and the uptake of amino acids. Insulin's actions are antagonistic to those of glucagon and the gluticocorticoids. Underproduction of insulin, or insensitivity to insulin, leads to diabetes mellitus, which is characterized by hyperglycemia (high blood glucose levels). Diabetes is the most common endocrine disorder and, if not treated, can lead to long-term complications involving the eyes, nerves, kidneys, and blood vessels.

Mineralocorticoids

Mineralocorticoids, particularly aldosterone, regulate plasma levels of sodium and potassium and, consequently, the total extracellular fluid volume. Aldosterone causes active reabsorption of sodium and passive reabsorption of water in the nephron of the kidney. This results in an increase in both blood volume and blood pressure. Excess production of aldosterone results in excess retention of water with resulting hypertension (high blood pressure). The mineralocorticoids are stimulated by angiotensin II and inhibited by ANP (atrial natiuretic peptide)

Interactions with the posterior pituitary

Neurosecretory cells in the hypothalamus synthesize both oxytocin and ADH and transport them via their axons into the posterior pituitary for storage and secretion.

Oxytocin

Oxytocin, which is secreted during childbirth, increases the strength and frequency of uterine muscle contractions. Oxytocin secretion is also induced by suckling; oxytocin stimulates milk secretion in the mammary glands.

Peptides

Peptide hormones range from simple short peptides (amino acid chains), such as ADH, to complex polypeptides, such as insulin. Peptide hormones act as first messengers. When they bind to specific receptors on the surface of their target cells, they trigger a series of enzymatic reactions within each cell, the first of which may be the conversion of ATP to cyclic adenosine monophosphate (cyclic AMP); this reaction is catalyzed by the membrane bound enzyme adenylate cyclase. Cyclic AMP acts as a second messenger, relaying messages from the extracellular peptide hormone to cytoplasmic enzymes and initiating a series of reactions in the cell. This is an example of a cascade effect; with each step, the hormone's effects are amplified. Cyclic AMP activity is inactivated by the cytoplasmic enzyme phosphodiesterase.

Steroids

Steroid hormones, such as estrogen and aldosterone, belong to a class of lipid-derived molecules with a characteristic ring structure. They are produced by the testes, ovaries, placenta, and adrenal cortex. Because they are lipid soluble, steroid hormones cross the phospholipid bilayer and enter their target cells directly in order to bind to specific receptor proteins in the cytoplasm. This receptor-hormone complex enters the nucleus and directly activates the expression of specific genes by binding to receptors on the chromatin. This induces a change in mRNA transcription and protein synthesis.

Adrenal medulia

The adrenal medulia produces epinephrine (adrenaline) and norepinephrine (nonadrenaline), both of which belong to a class of amino acid derived compounds called catecholamines. Epinephrine increases the conversion of glycogen to glucose in the liver and muscle tissue, causing an increase in blood glucose levels and an increase in the basal metabolic rate. Both epinephrine and norepinephrine increase the rate and strength of the heartbeat and dilate and constrict blood vessels in such a way as to increase the blood supply to the skeletal muscles, heart, and brain, while decreasing the blood supply to the kidneys, skin, and digestive tract. Both epinephrine and norepinephrine will also promote the release of lipids by adipose tissue. These effects are known as the fight or flight response and are elicited by sympathetic nervous stimulation in response to stress.

Anterior Pituitary

The anterior pituitary synthesizes both direct hormones, which directly act on their target organs, and tropic hormones, which stimulate other endocrine glands to release hormones. The hormonal secretions of the anterior pituitary are regulated by hypothalamic hormones called releasing/inhibiting hormones or factors.

Direct Hormones

The direct hormones of the anterior pituitary gland include: - Prolactin: Prolactin stimulates milk production in female mammary glands - Endorphins: These are neurotransmitters that have pain relieving properties - Growth hormone (GH, somatotropin): GH promotes bone and muscle growth. GH also promotes protein synthesis and lipid metabolism and catabolism. In children, a GH deficiency can lead to stunted growth (dwarfism), while overproduction of GH results in gigantism. Overproduction of GH in adults causes acromegaly, a disorder characterized by a disproportionate overgrowth of bone, especially in the skull, jaw, feet, and hands. - Melanocyte stimulating hormone (MSH): MSH is secreted by the intermediate lobe of the pituitary. In mammals, the function of MSH is unclear, but in frogs, MSH causes darkening of the skin via the induced dispersion of molecules of pigment in melanophore cells.

Hypothalamus

The hypothalamus is part of the forebrain and is located directly above the pituitary gland. The hypothalamus receives neural transmissions from other parts of the brain and from peripheral nerves that trigger specific responses from its neurosecretory cells. The neurosecretory cells regulate pituitary gland secretions via negative feedback mechanisms and through the actions of inhibiting and releasing hormones.

Pancreas

The pancreas is both an endocrine and exocrine organ. The exocrine function is performed by the cells the secrete digestive enzymes into the small intestine via a series of ducts. The endocrine function is performed by small glandular structures called the islets of Langerhans, which are composed of alpha and beta cells. Alpha cells produce and secrete glucagon; beta cells produce and secrete insulin. The endocrine hormones secreted by the pancreas is glucagon and insulin.

Parathyroid Glands

The parathyroid glands are four small, pea-shaped structures embedded in the posterior surface of the thyroid. These glands synthesize and secrete parathyroid hormone (PTH), which regulates plasma Ca concentration. PTH raises the Ca concentration in the blood by stimulating Ca release from the bone and decreasing Ca excretion in the kidneys. Calcium in bone is bonded to phosphate, and breakdown of the bone releases phosphate as well as calcium. Parathyroid hormone compensates for this by stimulating excretion of phosphate by the kidneys.

Pineal Gland

The pineal gland is a tiny structure at the base of the brain that secretes the hormone melatonin. The role of melatonin in humans is unclear, but is believed to play a role in the regulation of circadian rhythms - physiological cycles lasting approximately 24 hours. Melatonin secretion is regulated by light and dark cycles in the environment. In primitive vertebrates, melatonin lightens the skin by concentrating pigment granules in melanophores (melatonin is an antagonist to MSH)

Pituitary Gland

The pituitary (hydrophysis) is a small, trilobed gland at the base of the brain. The two main lobes, anterior and posterior, are functionally distinct. Specifically, the pituitary gland hangs below the hypothalamus and is connected to it by a slender cord known as the infundibulum

Posterior Pituitary

The posterior pituitary (neurohypohysis) does not synthesize hormones; it stores and releases the peptide hormones oxytocin and antidiuretic hormone, which are produced by the neurosecretory cells of the hypothalamus. Hormone secretion is stimulated by action potentials descending from the hypothalamus.

Thyroid hormones thyroxine and triiodothyronine

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are formed from the glycoprotein thyroglobulin, which is synthesized in thyroid cells. Because of the specific tertiary structure of this glycoprotein, iodinated tyrosine residues present in thyroglobulin are able to bind together to form active thyroid hormones.

Thyroid

Thyroid hormones affect the function of nearly every organ system in the body. In children, thyroid hormones are essential for growth and neurological development; in adults, thyroid hormones increase the rate of metabolism throughout the body and are essential for maintenance of metabolic stability.

Tropic Hormones

Tropic hormones of the anterior pituitary gland include: - Follicle stimulating hormone (FSH): In women, FSH causes maturation of ovarian follicles, which in turn secrete estrogen; in men, FSH stimulates maturation of the seminiferous tubules and sperm production - Luteinizing hormone (LH): In women, LH stimulates ovulation and maintenance of the corpus luteum. LH is also responsible for regulating progesterone secretion in women. In men, LH stimulates the interstitial cells of the testes to synthesize testosterone. - Thyroid-stimulating hormone (TSH): TSH stimulates the thyroid gland to synthesize and release thyroid hormones, including thyroxine.

Kidneys

When blood volume falls, the kidneys produce renin - an enzyme that converts the plasma protein angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II, which stimulates the adrenal cortex to secrete aldosterone. Aldosterone helps restore blood volume by increasing sodium reabsorption by the kidneys, leading to an increase in fluid retetion. This removes the initial stimulus for renin production. The kidneys also produce erythropoietin (EPO). EPO is a glycoprotein that stimulates red blood cell production; it is normally produced in the kidneys.