Adrenal cortex Androgen

The adrenal cortex is functionally divided into three zones, the zona glomerulosa, fasciculata, and reticularis. Only the outermost zone, the zona glomerulosa, synthesizes aldosterone. The other zones are responsible for the generation of glucocorticoids and androgens. 

The major androgen or androgen precursor produced by the adrenal cortex is dehydroepiandrosterone (DHEA). Most 17-hydroxypregnenolone follows the glucocorticoid pathway, but a small fraction is subjected to oxidative fission and removal of the two-carbon side chain through the action of 17,20-lyase. The lyase activity is actually part of the same enzyme (P450cl7) that catalyzes 17tt-hydroxylation. This is therefore a dual function protein. The lyase activity is important in both the adrenals and... 

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

Primary adrenal insufficiency (Addison s disease) most often involves the destruction of all regions of the adrenal cortex. There are deficiencies of cortisol, aldosterone, and the various androgens. Medications that inhibit cortisol synthesis (e.g., ketoconazole) or accelerate cortisol metabolism (e.g., phenytoin, rifampin, phenobarbital) can also cause primary adrenal insufficiency. 

The interaction between the adrenal cortex of the foetus and the placenta in production of steroid hormones is complex. In outline, the placenta produces progesterone from cholesterol (which is available from the maternal blood) whereas the foetal adrenal cortex produces corticosteroids and androgens from the progesterone produced in the placenta. The placenta then converts some of these androgens into oestrogens. The interplay between the placenta and the foetal adrenal cortex is acknowledged by the use of the term foeto-placental unit to describe steroido-... 

Pharmacology Testosterone, produced by the Leydig cells of the testis, is the primary natural androgen. In women, small amounts are synthesized by the ovary and adrenal cortex. 

Androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S) are other mildly androgenic compounds of secondary importance in males and females. The gonads and the adrenal cortex are capable of secreting androstenedione... 

The secretion of estrogens in females and androgens in males by the adrenal cortex is controlled by ACTH. They are responsible for the development and maintenance of secondary sexual characters in both males and females. They also increase the deposition of protein in muscles and reduce the excretion of nitrogen in males. 

Adrenal cortex also produces small quantities of weak androgens (androstenedione and dehydroepiandrosterone) which are partially converted to testosterone in peripheral tissues. In females, ovaries also secrete small quantities of testosterone. 

AdrenocorticotrophicAnterior Stimulates adrenal cortex to secrete hormone (ACTH) pituitary glucocorticoids, mineralocorticoids, and Melanocyte- androgens stimulates melanocytes ... 

Adrenocorticotropin (ACTH) Corticotropin-releasing hormone (CRH)(+) Adrenal cortex Glucocorticoids, mineralocorticoids, androgens... 

Steroid hormones are secreted on demand from their tissues of origin in response to hormonal signals. The corticosteroids and androgens are made in different regions of the adrenal cortex, and are secreted into blood in response to different signals. 

Androgens Both the inner and middle layers of the adrenal cortex produce androgens, primarily dehydroepiandrosterone and androstenedione. Although adrenal androgens themselves are weak, they are converted in peripheral tissues to testosterone—a strong androgen—and to estradiol. 

The primary function of AC. TH is the stimulation of the adrenal cortex to produce its hormones, which have already been discussed. This is evideni from the therapeutic effect of administration of ACTH. which is closely similar to that of Ihese hormones, so that if ihe action of only one of them is sought, its administration is preferable, Moreover. ACTH stimulates secretion of the androgenic substances mentioned as produced by the adrenal cortex. 

The adrenocorticotrophic hormone ACTH (corticotropin) stimulates the adrenal cortex to secrete the glucocorticoids hydrocortisone (cortisol) and corticosterone, the mineralocorticoid aldosterone, and a number of weakly androgenic substances, as well as a small amount of testosterone. Aldosterone synthesis is also regulated by renin and angiotensin. 

Hormones of the Adrenal Cortex. The adrenal cortex synthesizes and secretes two primary groups of steroidal hormones the glucocorticoids and the min-eralocorticoids.41 Small amounts of sex steroids (estrogens, androgens, progesterone) are also produced, but these amounts are essentially insignificant during normal adrenal function. 

This chapter discusses the pharmacology of the steroid hormones that are produced by the adrenal cortex. The two primary types of adrenal steroids are the glucocorticoids and mineralocorticoids. Small amounts of other steroids such as the sex hormones (androgens, estrogens, and progestins) are also produced by the adrenal cortex. These steroids are discussed in Chapter 30. 

Male and female hormones are produced primarily in the gonads. Androgens are synthesized in the testes in the male. In the female, the ovaries are the principal sites of estrogen and progestin production. As discussed in Chapter 29, small amounts of sex-related hormones are also produced in the adrenal cortex in both sexes, which accounts for the fact that small amounts of hormones of the opposite sex are seen in females and males that is, low testosterone levels are seen in females, and males produce small quantities of estrogen. However, under normal conditions, the amounts of sex-related hormones produced by the adrenal cortex are usually too small to produce significant physiologic effects. 

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