7.15: Adrenal Glands

Adrenal Cortex

In the adrenal cortex, several distinct zones are characterized by layers of lipid-storing cells, each responsible for producing specific hormones.

Mineralocorticoids

The outermost layer of the adrenal cortex, known as the zona glomerulosa, plays a pivotal role in synthesizing a group of hormones called mineralocorticoids. These hormones, primarily exemplified by aldosterone, influence body minerals, particularly sodium and potassium ions, thus contributing significantly to regulating fluid and electrolyte balance.

Aldosterone, the primary mineralocorticoid, is essential for regulating the levels of sodium and potassium ions in bodily fluids. Its secretion is carefully regulated in response to several physiological signals, such as increased blood potassium levels, decreased blood sodium levels, lowered blood pressure, or reduced blood volume. The release of aldosterone is initiated by CRH from the hypothalamus, which triggers the anterior pituitary gland to release ACTH (Figure 26). Moreover, aldosterone plays a pivotal role within the renin-angiotensin-aldosterone system (RAAS), a complex physiological pathway. In response to conditions such as low blood volume or low blood pressure, specialized kidney cells release the enzyme renin. Renin catalyzes the conversion of angiotensinogen, a blood protein synthesized in the liver, into angiotensin I. This precursor hormone, angiotensin I, is subsequently transformed into angiotensin II in the lungs through the action of angiotensin-converting enzyme (ACE). Angiotensin II serves several crucial functions such as inducing vasoconstriction of the arterioles, resulting in decreased blood flow and signaling the adrenal cortex to secrete aldosterone, which enhances fluid retention, subsequently elevating blood volume and blood pressure (Figure 27). While reabsorbing sodium ions and eliminating potassium ions at the renal tubules, aldosterone indirectly stimulates the reabsorption of water contributing to increased blood volume and blood pressure. ACE inhibitors, a class of medications, function by blocking the activity of ACE, thus preventing the conversion of angiotensin I to angiotensin II. By doing so, they effectively inhibit an increase in blood pressure associated with the RAAS pathway.

​Figure 26 | The Aldosterone Feedback Loop | ²⁹

​Figure 27 | Schematic representation of the Renin-Angiotensin-Aldosterone System (RAAS) | ²⁸ This hormonal cascade begins with the release of renin from the juxtaglomerular cells of the kidneys in response to low blood pressure. Renin converts angiotensinogen, produced by the liver, into angiotensin I. Angiotensin I is then converted to angiotensin II by the angiotensin-converting enzyme (ACE) primarily in the lungs. Angiotensin II stimulates vasoconstriction, increases blood pressure, and promotes the release of aldosterone from the adrenal cortex. Aldosterone enhances sodium reabsorption in the kidneys, leading to increased water retention, blood volume, and further elevation of blood pressure. 

Glucocorticoids

Located in the intermediate region of the adrenal cortex, the zona fasciculata derives its name from the distinctive arrangement of its cells, which form small bundles known as fascicles, interspersed with minute blood vessels. The primary hormones synthesized within the zona fasciculata are categorized as glucocorticoids due to their pivotal role in glucose metabolism. Cortisol, also known as hydrocortisone, is a major glucocorticoid. In addition to cortisol, a fraction is converted into cortisone and corticosterone in the liver.

Long-term stressors trigger a cascade of hormonal responses. Initially, the CRH stimulates the anterior pituitary to release ACTH, which, in turn, acts on the adrenal cortex, eliciting the secretion of glucocorticoids, as illustrated in Figure 28.

Cortisol exhibits a diurnal secretion pattern, peaking in the early morning hours, typically before the onset of physical activity. The primary overarching effect of cortisol is to inhibit tissue growth and simultaneously stimulate the breakdown of stored nutrients, ensuring a continuous supply of essential fuel sources. During prolonged stress conditions, cortisol promotes the catabolism of glycogen into glucose, converts stored triglycerides into fatty acids and glycerol, and facilitates the breakdown of muscle proteins into amino acids. These raw materials are then used to synthesize additional glucose and ketones, serving as crucial energy sources for the body. Furthermore, cortisol exhibits immunosuppressive properties by diminishing the activity of key immune cells such as macrophages and T-lymphocytes, resulting in an anti-inflammatory effect. This unique characteristic of cortisol has significant clinical applications, as it is employed to treat inflamed joints, manage severe asthma, and alleviate pruritic skin rashes.

Androgens

Located in the deepest region of the adrenal cortex, the zona reticularis produces trace amounts of androgens, including androstenedione and dehydroepiandrosterone. In response to ACTH secreted by the anterior pituitary, these androgens are synthesized and subsequently converted to testosterone or estrogens within various tissues. While these minimal levels of androgens may play a role in female libido, their significance in adult males is diminished by the substantial testosterone output from the testes. However, in post-menopausal women, when ovarian functions wane, the primary source of estrogens shifts to the androgens produced by the zona reticularis.

Adrenal Medulla

As previously mentioned, the adrenal cortex releases glucocorticoids as part of the response to prolonged stress, such as severe illness. In contrast, the adrenal medulla functions differently, releasing its hormones in response to acute, short-term stress mediated by the sympathetic nervous system.

The adrenal medulla is composed of distinctive postganglionic sympathetic neurons called chromaffin cells. These cells are characterized by their large and irregular shapes and are responsible for producing the neurotransmitters epinephrine and norepinephrine. Epinephrine is produced in higher quantities, maintaining a ratio of approximately 4 to 1 with norepinephrine, and is the more potent hormone of the two. Because chromaffin cells release epinephrine and norepinephrine into the systemic circulation, where they travel extensively to exert their effects on distant cells, they are classified as hormones. The secretion of epinephrine and norepinephrine from the adrenal medulla is regulated by a neural pathway initiated by the hypothalamus in response to threats or stressors. Both hormones signal the liver and skeletal muscle cells to convert glycogen into glucose, increasing blood glucose levels. Additionally, they elevate heart rate and blood pressure, preparing the body for the "fight or flight" response. The neural pathway also dilates airways to enhance blood oxygen levels, promotes vasodilation to oxygenate vital organs such as the lungs, brain, heart, and skeletal muscles, and constricts blood vessels serving less essential organs like the gastrointestinal tract, kidneys, and skin. This response suppresses certain components of the immune system while also inducing effects such as dry mouth, decreased appetite, pupil dilation, and peripheral vision loss. Table 7 provides an overview of the main hormones produced by different regions of the adrenal glands, detailing their chemical characteristics and primary effects on the body.³⁰