Located at the top of each kidney, they are responsible for releasing different kinds of hormones.
The outer part of the gland, called the adrenal cortex, produces the hormones cortisol and aldosterone. The inner part of the gland, called the adrenal medulla, stimulates the hormones adrenaline and noradrenaline.
The adrenal cortex, the outer part of the gland, produces hormones that are vital to life, such as cortisol (which helps regulate metabolism and helps the body respond to stress) and aldosterone (which helps control blood pressure ).
The adrenal cortex comprises three zones: the glomerular, fascicular, and reticular zones.
Aldosterone, the most crucial bioactive mineralocorticoid in humans, is synthesized in the outermost zone of the glomerular.
This region of the adrenal cortex is regulated by the circulation of sodium, potassium, and angiotensin. The fascicular and reticular zone produce both cortisol and corticosterone. These adrenal regions, and to a much lesser extent of the glomerular area, are regulated by ACTH released from the anterior pituitary.
Hormones of the adrenal cortex
Cortisol and its synthetic analogs have had wide clinical use to treat a variety of disorders for more than 50 years.
Since its first clinical application, intensive research has broadened our understanding of steroids’ physiology, biochemistry, and pharmacology. It has led to a large body of literature addressing corticosteroids’ therapeutic use and harmful side effects.
This chapter reviews the pharmacology and physiology of corticosteroids, discusses the use of these hormonal agents in the treatment of neoplasms, and presents the mechanism of action currently known for corticosteroids in their therapeutic efficacy.
In the mid-nineteenth century, it was observed that the lack of functional adrenal glands was incompatible with life. Subsequent research classified the effects of adrenal insufficiency into two distinct groups: those due to electrolyte imbalance and those due to alterations—in the metabolism of carbohydrates.
The hypercritical syndrome was described by Cushing in 1932. In the 1940s and 1950s, the adrenocorticotropic hormone (ACTH) was identified in the anterior part of the pituitary gland and was described as a stimulator of the adrenal cortex.
Several bioactive steroids, including cortisol and aldosterone (the main active corticosteroids in humans), were isolated from the adrenal cortex and characterized.
In 1949, Hench reported the efficacy of cortisol and ACTH in the treatment of rheumatoid arthritis for the first time. This observation quickly extended to therapeutic applications in a wide variety of diseases.
This broad clinical interest stimulated the intense investigation of these compounds. In the following decade, most of the biochemistry involved in the synthesis and metabolism of adrenocortical steroids was elucidated.
During this period, the field of corticosteroid therapy progressed rapidly since most of the currently available synthetic corticosteroid analogs were developed, and practical methods of determining cortisol in plasma were identified.
In the intervening years, analogs of synthetic corticosteroids were developed to separate anti-inflammatory and electrolyte balance effects.
However, despite the continuous effort, the successful separation of clinical efficacy from harmful side effects has not been achieved.
Consequently, the chronic use of these powerful drugs is limited by their slow and cumulative profile of side effects. The damage associated with corticosteroid therapy may not be apparent until catastrophic consequences.
Five steroid hormones are produced in the adrenal cortex: glucocorticoids, mineralocorticoids, progestins, androgens, and estrogens.
However, the amount of progestin, androgen, and estrogen produced by the adrenal gland is a smaller fraction of the total amount of these steroids produced in the body.
In contrast, glucocorticoids and mineralocorticoids occur almost exclusively in the adrenal cortex.
Glucocorticoids have a broad physiological role that includes both the regulation of the metabolic pathways of glucose and the modulation of the immune system. Mineralocorticoids are critical regulators of the water and mineral balance.
Corticosteroid biosynthesis has been well characterized. Cholesterol, the precursor of all steroid biosynthetic pathways, becomes a variety of steroid molecules in reactions catalyzed by several cytochrome P450 enzymes (cyp 450).
While some cholesterol can be synthesized in the adrenal cortex, most of the cholesterol used in steroid biosynthesis is taken from a set of circulating cholesterol bound to low-density lipoproteins in the plasma.