Adrenocortical Hormones

Abnormalities of Adrenocortical Secretion

1. Hypoadrenalism (Adrenal Insufficiency)—Addison's Disease Inability of the adrenal cortices to produce sufficient adrenocortical hormones. In about 80 percent of the cases, the atrophy is caused by autoimmunity against the cortices. Adrenal gland hypofunction may also be caused by tuberculous destruction of the adrenal glands or invasion of the adrenal cortices by cancer. In some cases, adrenal insufficiency is secondary to impaired function of the pituitary gland, which fails to produce sufficient ACTH.

Physiological Regulation of Aldosterone Secretion

1. Increased potassium ion concentration in the extracellular fluid greatly increases aldosterone secretion. 2. Increased angiotensin II concentration in the extracellular fluid also greatly increases aldosterone secretion. 3. Increased sodium ion concentration in the extracellular fluid very slightly decreases aldosterone secretion. Note: Potassium ion concentration and the renin-angiotensin system- most potent in regulating aldosterone secretion. A small percentage increase in potassium concentration can cause a several fold increase in aldosterone secretion. Activation of the renin-angiotensin system, usually in response to diminished blood flow to the kidneys or to sodium loss, can increase aldosterone secretion several fold. The aldosterone acts on the kidneys (1) to help them excrete the excess potassium ions and (2) to increase the blood volume and arterial pressure, thus returning the renin-angiotensin system toward its normal level of activity.

The Adrenal Cortex Has Three Distinct Layers

1. The zona glomerulosa: aldosterone The secretion of these cells is controlled mainly by the extracellular fluid concentrations of angiotensin II and potassium, both of which stimulate aldosterone secretion. 2. The zona fasciculata (the middle and widest zone): secretes the glucocorticoids cortisol and corticosterone and small amounts of adrenal androgens and estrogens The secretion is controlled in large part by the hypothalamic-pituitary axis via adrenocorticotropic hormone (ACTH) 3. The zona reticularis (the inner zone of the cortex): secretes the adrenal androgens dehydroepiandrosterone and androstenedione, as well as small amounts of estrogens and some glucocorticoids ACTH also regulates secretion of these cells, although other factors such as cortical androgen-stimulating hormone, released from the pituitary, may also be involved

When large amounts of cortisol are secreted or injected into a person, the glucocorticoid has two basic anti-inflammatory effects:

1. it can block the early stages of the inflammation process before noticeable inflammation even begins, or 2. if inflammation has already begun, it causes rapid resolution of the inflammation and increased rapidity of healing.

Cortisol is Important in Resisting Stress and Inflammation

Almost any type of stress, whether physical or neurogenic, causes an immediate and marked increase in ACTH secretion by the anterior pituitary gland, Increased adrenocortical secretion of cortisol. The following list details some of the different types of stress that increase cortisol release: 1.Trauma; 2.Infection; 3.Intense heat or cold 4.Injection of norepinephrine and other sympathomimetic drugs; 5.Surgery; 6.Injection of necrotizing substances beneath the skin; 7.Restraining an animal so it cannot move 8.Debilitating diseases

Adrenocortical Hormones Are Bound to Plasma Proteins.

Approximately 90 to 95 percent of the cortisol in the plasma binds to plasma proteins- a globulin called cortisol-binding globulin or transcortin and, to a lesser extent, to albumin. Only about 60 percent of circulating aldosterone combines with the plasma proteins, so about 40 percent is in the free form Binding of adrenal steroids to the plasma proteins may serve as a reservoir to lessen rapid fluctuations in free hormone concentrations This reservoir function may also help to ensure a relatively uniform distribution of the adrenal hormones to the tissues.

Physiological Functions of Glucocorticoids

At least 95 percent of the glucocorticoid activity of the adrenocortical secretions results from the secretion of cortisol (hydrocortisone).

Cellular Mechanism of Aldosterone Action

Because of its lipid solubility in the cellular membranes, aldosterone diffuses readily to the interior of the tubular epithelial cells In the cytoplasm of the tubular cells- aldosterone combines with a highly specific cytoplasmic mineralocorticoid receptor (MR) protein The aldosterone-receptor complex diffuses into the nucleus Finally inducing one or more specific portions of the DNA to form one or more types of messenger RNA (mRNA) related Leads to the formation of the specific intracellular substances required for sodium transport

Glucocorticoids

Cortisol (very potent; accounts for about 95 percent of all glucocorticoid activity) Corticosterone (provides about 4 percent of total glucocorticoid activity, but is much less potent than cortisol) Cortisone (almost as potent as cortisol) Prednisone (synthetic; four times as potent as cortisol) Methylprednisone (synthetic; five times as potent as cortisol) Dexamethasone (synthetic; 30 times as potent as cortisol)

Abnormalities of Adrenocortical Secretion

Glucocorticoid Deficiency. Difficulty to maintain normal blood glucose concentration between meals because he or she cannot synthesize significant quantities of glucose by gluconeogenesis. Reduces the mobilization of both proteins and fats from the tissues, thereby depressing many other metabolic functions of the body. Lack of adequate glucocorticoid secretion also makes a person with Addison's disease highly susceptible to the deteriorating effects of different types of stress, and even a mild respiratory infection can cause death.

Physiological Functions of the Mineralocorticoids—Aldosterone

Mineralocorticoid Deficiency Causes Severe Renal Sodium Chloride Wasting and Hyperkalemia. The mineralocorticoids are said to be the acute "lifesaving" portion of the adrenocortical hormones Aldosterone Is the Major Mineralocorticoid Secreted by the Adrenals.

Abnormalities of Adrenocortical Secretion

Mineralocorticoid Deficiency. Decreases renal tubular sodium reabsorption and consequently allows sodium ions, chloride ions, and water to be lost into urine in great profusion. Decreased extracellular fluid volume. Hyponatremia, hyperkalemia, and mild acidosis develop because of failure of potassium and hydrogen ions to be secreted in exchange for sodium reabsorption. Plasma volume falls, red blood cell concentration rises markedly, cardiac output and blood pressure decrease, Patient dies in shock, with death usually occurring in the untreated patient 4 days to 2 weeks after complete cessation of mineralocorticoid secretion

Effects of Cortisol on Fat Metabolism

Mobilization of Fatty Acids: increases the concentration of free fatty acids in the plasma

Adrenal Androgens

Moderately active male sex hormones called adrenal androgens Most important- dehydroepiandrosterone Continually secreted by adrenal cortex, especially during fetal life progesterone and estrogens (female sex hormones)- secreted in minute quantities

Effects of Cortisol on Protein Metabolism

Reduction in Cellular Protein: the muscles become weak

Effects of Cortisol on Carbohydrate Metabolism

Stimulation of Gluconeogenesis by the liver: the formation of carbohydrate from proteins and some other substances Decreased Glucose Utilization by Cells: to decrease translocation of the glucose transporters GLUT 4 to the cell membrane, especially in skeletal muscle cells, leading to insulin resistance Elevated Blood Glucose Concentration and "Adrenal Diabetes."

Adrenal Glands

The two adrenal glands, each of which weighs about 4 grams, lie at the superior poles of the two kidneys. Each gland is composed of two major parts, the adrenal medulla and the adrenal cortex. Secretes epinephrine and norepinephrine in response to sympathetic stimulation. The adrenal cortex secretes an entirely different group of hormones - corticosteroids.

Corticosteroids: Mineralocorticoids, Glucocorticoids, and Androgens

Two major types of adrenocortical hormones: the mineralocorticoids and the glucocorticoids. Secreted by the adrenal cortex. The mineralocorticoids have gained this name because they especially affect the electrolytes (the "minerals") of the extracellular fluids, especially sodium and potassium. The glucocorticoids have gained their name because they exhibit important effects that increase blood glucose concentration. They have additional effects on both protein and fat metabolism that are equally as important to body function as their effects on carbohydrate metabolism. Aldosterone- principal mineralocorticoid. Cortisol- principal glucocorticoid.

Anti-inflammatory Effects of High Levels of Cortisol

When tissues are damaged by trauma, by infection with bacteria, or in other ways, they almost always become "inflamed." In some conditions, such as in rheumatoid arthritis, the inflammation is more damaging than the trauma or disease itself. Administration of large amounts of cortisol can usually block this inflammation or even reverse many of its effects once it has begun.

Abnormalities of Adrenocortical Secretion

2. Hyperadrenalism—Cushing's Syndrome Cushing's syndrome- hypersecretion by the adrenal cortex Amounts of cortisol + excess secretion of androgens Causes: (1) adenomas of the anterior pituitary that secrete large amounts of ACTH, which then causes adrenal hyperplasia and excess cortisol secretion; (2) abnormal function of the hypothalamus that causes high levels of corticotropin-releasing hormone, which stimulates excess ACTH release; (3) "ectopic secretion" of ACTH by a tumor elsewhere in the body, such as an abdominal carcinoma; and (4) adenomas of the adrenal cortex. When Cushing's syndrome is secondary to excess secretion of ACTH by the anterior pituitary, this condition is referred to as Cushing's disease. Cushing's syndrome can also occur when large amounts of glucocorticoids are administered over prolonged periods for therapeutic purposes. For example, patients with chronic inflammation associated with diseases such as rheumatoid arthritis are often treated with glucocorticoids and may experience some of the clinical symptoms of Cushing syndrome. A special characteristic of Cushing's syndrome is mobilization of fat from the lower part of the body, with concomitant extra deposition of fat in the thoracic and upper abdominal regions, giving rise to a buffalo-like torso. The excess secretion of steroids also leads to an edematous appearance of the face, and the androgenic potency of some of the hormones sometimes causes acne and hirsutism (excess growth of facial hair). The appearance of the face is frequently described as a "moon face,"

Excess Cortisol Causes Obesity

A peculiar type of obesity- in many people with excess cortisol secretion, with excess deposition of fat in the chest and head regions of the body, giving a buffalo-like torso and a rounded "moon face." Cause is unclear Obesity results from excess stimulation of food intake, with fat being generated in some tissues of the body more rapidly than it is mobilized and oxidized.

Mineralocorticoids

Aldosterone (very potent; accounts for about 90 percent of all mineralocorticoid activity) Deoxycorticosterone (1/30 as potent as aldosterone, but very small quantities are secreted) Corticosterone (slight mineralocorticoid activity) 9α-Fluorocortisol (synthetic; slightly more potent than aldosterone) Cortisol (very slight mineralocorticoid activity, but a large quantity is secreted) Cortisone (slight mineralocorticoid activity)

Renal and Circulatory Effects of Aldosterone

Aldosterone Increases Renal Tubular Reabsorption of Sodium and Secretion of Potassium. Excess Aldosterone Increases Extracellular Fluid Volume and Arterial Pressure but has only a small effect on plasma sodium concentration. Excess Aldosterone Causes Hypokalemia and Muscle Weakness. Aldosterone Deficiency Causes Hyperkalemia and Cardiac Toxicity. Excess Aldosterone Increases tubular hydrogen ion Secretion and Causes Alkalosis.