The Endocrine System / The Adrenal Glands

submitted by Dr. Gary Farr Last Updated June, 28, 2003

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What is it?

The adrenal glands which are also called the suprarenal glands, are small, triangular glands located on top of both kidneys. An adrenal gland is made of two parts: the outer region is called the adrenal cortex and the inner region is called the adrenal medulla. Both parts of the adrenal glands -- the adrenal cortex and the adrenal medulla -- perform very separate functions.

The adrenal glands work interactively with the hypothalamus and pituitary gland in the following process:

• the hypothalamus produces corticotropin-releasing hormones, which stimulate the pituitary gland.
• the pituitary gland, in turn, produces corticotropin hormones, which stimulate the adrenal glands to produce corticosteroid hormones.

We'll describe each part individually:

The Adrenal Cortex

Anatomy

The outer covering (adrenal cortex) is derived from the fetal mesodermal ridge, a structure that also gives rise to the kidneys so that the juxtaposition of the two organs is not surprising. Within the adrenal cortex are three zones known as the outer (zona glomerulosa), the middle (zona fasciculata), and the inner (zona reticularis). Under the microscope the cells are rather typical endocrine cells; the distinction between zones is made by differing staining characteristics.

Adrenal Cortex Functions

The adrenal cortex, the outer portion of the adrenal gland, secretes hormones that have an effect on the body's metabolism, on chemicals in the blood, and on certain body characteristics. The adrenal cortex secretes corticosteroids and other hormones directly into the bloodstream. The hormones produced by the adrenal cortex include:

• corticosteroid hormones

• hydrocortisone hormone - this hormone, also known as cortisol, controls the body's use of fats, proteins, and carbohydrates.
• corticosterone - this hormone, together with hydrocortisone hormones, suppresses inflammatory reactions in the body and also affects the immune system.

• aldosterone hormone - this hormone inhibits the level of sodium excreted into the urine, maintaining blood volume and blood pressure.
• androgenic steroids (androgen hormones) - these hormones have minimal effect on the development of male characteristics

Hormones

Adrenocortical cells synthesize and secrete chemical derivatives (steroids) from cholesterol, the major animal sterol. While cholesterol can be synthesized in many body tissues, further differentiation into steroid hormones takes place only in the adrenal cortex and in its embryological cousins, the ovaries and the testes.

The adrenal cortex is capable of synthesizing all of the steroid hormones produced by the body, including the progestogens and estrogens (see the ovary), androgens (see the testis), mineralocorticoids (which are secreted from the zona glomerulosa), and glucocorticoids (which are synthesized and released from the zona fasciculata and zona reticularis of the adrenal cortex). Although upwards of 60 steroids are manufactured in the adrenal cortex, only a few members of these three major categories are important in body functioning.

Aldosterone

The biologic effect of aldosterone, the principal mineralocorticoid, is to set in motion a set of reactions at the cell surface of all body tissues in order to enhance the uptake and retention of sodium in all cells and the extrusion of potassium from them. It also has a major impact on kidney function, to retain sodium within the circulation while increasing the excretion of potassium into the urine. At the same time, aldosterone tends to decrease the acidity of body fluids.

Cortisol

Cortisol (hydrocortisone) is the major human glucocorticoid. It exerts multiple and varied effects. It also serves as a mineralocorticoid but is considerably less effective than aldosterone. Cortisol plays a major role in the body's response to stress. In fasting, for example, it sustains the blood sugar concentration by blocking the egress of glucose into all tissues other than the critically important brain and spinal cord, while it simultaneously increases the breakdown of protein from muscle and other organs and hastens the conversion of newly generated amino acids to glucose to replenish the supply constantly being consumed by the brain.

Cortisol, along with more potent and longer-acting synthetic derivatives like prednisone, methylprednisolone, and dexamethasone exerts powerful anti-inflammatory effects. Physicians take advantage of these properties in treating patients with serious inflammatory illnesses such as rheumatoid arthritis, disseminated lupus erythematosus, and multiple sclerosis. If, however, the inflammation has a bacterial or viral origin, the steroids may do more harm than good because the spread of the infection is facilitated while the signs of inflammation are masked (see immune system). Finally, corticosteroids in large doses impair the functioning of the immune system so that the production of harmful antibodies, such as those produced in allergic diseases, may be suppressed. It is important to note that these beneficial effects are offset by serious side effects of large-dose, long-term corticosteroid therapy, effects that closely mimic many of the symptoms of Cushing's syndrome (see below).

Adrenal androgens

Adrenal androgens are not as potent as testosterone, the major steroid secreted by the testis, but a number of them, including androstenedione, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) may be converted to stronger androgens such as testosterone. Although little androgen is secreted before puberty, the output increases dramatically at puberty so that the adrenal cortex makes a significant contribution, known as the adrenarche, to developmental changes in both sexes.

Regulation of hormone secretion

The three classes of corticosteroids (the mineralocorticoids, the glucocorticoids, and the adrenal androgens) are regulated largely by separate mechanisms. Glucocorticoids are regulated by way of the classical hypothalamic-hypophyseal feedback system. Within the family of glucocorticoids, the cortisol level is the one most closely guarded. Furthermore, the ongoing feedback control is modulated by hypothalamic biorhythmic activity illustrated in the case of cortisol in the figure to the left. When the individual is exposed to physical or emotional stress, the self-regulating mechanism is interrupted and plasma cortisol is increased to deal with the stress. Adrenal androgen secretion is controlled primarily by ACTH, although there is evidence that prolactin stimulates the secretion of adrenal androgens as well.

Aldosterone secretion is modulated directly by serum electrolyte levels. Lowered serum sodium concentrations enhance aldosterone secretion, but a far more potent stimulus is a high serum potassium level.

Aldosterone increases the reabsorption of sodium (and the excretion of potassium) by the distal tubules in the kidney. The reabsorption of sodium results in an increased reabsorption of water which can result in hypertension. Low blood aldosterone levels are seen in {addisons} Addison's disease and toxemia of pregnancy. Higher levels can be seen in {cushings} Cushing's syndrome, primary hyperaldosteronism, malignant hypertension, severe swelling in congestive heart failure, and nephrotic syndrome.

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