The adrenal glands are small, cap-shaped organs situated directly on top of the kidneys. Each gland is composed of two parts: an inner core called the medulla and a thick outer shell known as the adrenal cortex. The adrenal cortex is responsible for synthesizing and secreting a variety of steroid hormones derived from cholesterol. These hormones regulate metabolism, manage the body’s response to stress, and maintain electrolyte balance.
Three Distinct Layers of the Cortex
The adrenal cortex is organized into three concentric zones, each specialized for producing a different class of steroid hormones. The outermost layer is the zona glomerulosa. This zone is the site of mineralocorticoid synthesis, with aldosterone being the most prominent hormone, primarily involved in regulating the body’s mineral composition.
Deep to the zona glomerulosa lies the thickest layer, the zona fasciculata. This middle zone is the primary site for the production of glucocorticoids, such as cortisol. Glucocorticoids are important for regulating glucose metabolism and moderating inflammatory responses throughout the body.
The innermost layer, situated adjacent to the adrenal medulla, is called the zona reticularis. This zone is responsible for synthesizing androgens, which are sex hormones. While the ovaries and testes are the major sources of these hormones, the cortex contributes a small amount of precursors.
Essential Hormones and Their Roles
Glucocorticoids
Cortisol is the body’s main glucocorticoid, central to the body’s reaction to physical or psychological strain. Cortisol promotes gluconeogenesis, which is the liver’s process of synthesizing new glucose from non-carbohydrate sources like amino acids and fats. This action ensures that the brain has a continuous supply of energy during times of fasting or increased metabolic demand.
Cortisol also modulates the activity of the immune system. It helps to temper inflammation by suppressing the release of pro-inflammatory substances, preventing an excessive immune reaction. Cortisol influences the cardiovascular system by helping to maintain the responsiveness of blood vessels to vasoconstrictive substances, supporting stable blood pressure.
It also affects bone turnover and connective tissue repair. Cortisol’s broad influence means it affects nearly every tissue and organ system.
Mineralocorticoids
Aldosterone is the primary mineralocorticoid, specialized in maintaining the balance of salts and water in the body. Its main target is the epithelial cells lining the distal convoluted tubules and collecting ducts of the kidneys. Aldosterone stimulates the reabsorption of sodium ions (\(\text{Na}^{+}\)) from the filtrate back into the bloodstream.
The reabsorption of sodium is accompanied by the passive reabsorption of water, which helps to increase the total volume of blood. Simultaneously, aldosterone promotes the secretion of potassium ions (\(\text{K}^{+}\)) into the renal tubule for excretion in the urine.
By managing the movement of these electrolytes, aldosterone directly regulates extracellular fluid volume. Consequently, it plays a significant part in controlling systemic blood pressure.
Adrenal Androgens
The adrenal cortex produces a group of weak androgens, including dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S. These hormones are precursors that can be converted into more potent sex hormones, such as testosterone and estrogen, in peripheral tissues. While their contribution is minor in adult males, adrenal androgens are the main source of androgens in women after menopause.
In both sexes, these hormones contribute to the development of pubic and axillary hair during puberty, a process known as adrenarche. They also influence libido and muscle mass. These hormones serve primarily as a circulating reservoir for sex hormone synthesis elsewhere in the body.
How Hormone Release is Controlled
Glucocorticoid release is primarily governed by the Hypothalamic-Pituitary-Adrenal (HPA) axis. The process begins when the hypothalamus releases corticotropin-releasing hormone (CRH) in response to stressors or circadian rhythms. CRH then travels to the anterior pituitary gland, stimulating the release of adrenocorticotropic hormone (ACTH) into the general circulation.
ACTH acts directly on the cells of the zona fasciculata and zona reticularis, prompting them to synthesize and release cortisol. Once cortisol levels in the blood rise, the hormone feeds back to both the pituitary and the hypothalamus. This negative feedback mechanism inhibits the further release of ACTH and CRH, preventing excessive hormone levels.
Mineralocorticoid secretion is controlled by the Renin-Angiotensin-Aldosterone System (RAAS). This system is activated primarily in response to a drop in blood pressure or a decrease in sodium concentration. Specialized cells in the kidney release the enzyme renin, which initiates a cascade that ultimately leads to the formation of angiotensin II.
Angiotensin II then travels to the adrenal cortex, acting on the zona glomerulosa. This action stimulates the secretion of aldosterone.
Common Clinical Conditions
Disorders of the adrenal cortex involve either an overproduction or an underproduction of its steroid hormones, leading to clinical syndromes. Cushing’s Syndrome results from prolonged exposure to high levels of glucocorticoids, most commonly cortisol. This hypercortisolism can be caused by a pituitary tumor secreting too much ACTH or by a tumor within the adrenal gland itself. Symptoms include weight gain concentrated in the face and trunk, muscle weakness, and easy bruising due to the catabolic effects of excess cortisol.
Conversely, Addison’s Disease is a form of primary adrenal insufficiency where the cortex does not produce enough steroid hormones. This condition often involves the destruction of all three cortical layers, leading to deficiencies in both cortisol and aldosterone. A lack of aldosterone causes the body to lose sodium and retain potassium, which can lead to low blood pressure and dangerous electrolyte imbalances. Patients commonly experience chronic fatigue, unexplained weight loss, and a distinctive darkening of the skin.
Congenital Adrenal Hyperplasia (CAH) represents a group of genetic disorders where an enzyme needed for cortisol synthesis is defective. The resulting lack of cortisol triggers the HPA axis to overproduce ACTH, which stimulates the adrenal gland to grow. This overstimulation shunts precursor hormones into the androgen pathway, which can lead to ambiguous genitalia in newborn girls and premature development of secondary sex characteristics in both sexes.