Androstenedione secretion

The ceUular source of the various ovarian steroids has been difficult to unravel, but a transfer of substrates between two cell types is involved. Theca cells are the source of androstenedione and testosterone. These are converted by the aromatase enzyme in granulosa cells to estrone and estradiol, respectively. Progesterone, a precursor for all steroid hormones, is produced and secreted by the corpus luteum as an end-product hormone because these cells do not contain the enzymes necessary to convert progesterone ro other steroid hormones (Figure 42-8). 

Testosterone, the major androgenic hormone, accounts for 95% of the androgen concentration. The primary source of testosterone is the testes however, 3% to 5% of the testosterone concentration is derived from direct adrenal cortical secretion of testosterone or C-19 steroids such as androstenedione.17,18... 

The follicular phase covers the development of the follicle, which involves an increase in its size due to an increase in follicular fluid, growth of the ovum (i.e. an increase in the contents of RNA and protein) and an increase in the number of cells that surround the ovum. These cells are of two types, the granulosa and the thecal cells. The role of these cells is to synthesise and secrete the steroid hormones oestrogens (mainly oestradiol). The precursor molecule for their synthesis is cholesterol. There is a division of labour between these cells the thecal cells convert cholesterol into the male sex hormones androstenedione and testosterone, which are released into the blood to be taken up by the granulosa cells where they are converted to the oestrogens (Figure 19.8). For details of pathways, see Appendix 19.1. 

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... 

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. 

The ovary normally ceases its gametogenic and endocrine function with time. This change is accompanied by a cessation in uterine bleeding (menopause) and occurs at a mean age of 52 years in the USA. Although the ovary ceases to secrete estrogen, significant levels of estrogen persist in many women as a result of conversion of adrenal and ovarian steroids such as androstenedione to estrone and estradiol in adipose and possibly other nonendocrine tissues. 

In men, approximately 8 mg of testosterone is produced daily. About 95% is produced by the Leydig cells and only 5% by the adrenals. The testis also secretes small amounts of another potent androgen, dihydrotestosterone, as well as androstenedione and dehydroepiandrosterone, which are weak androgens. Pregnenolone and progesterone and their 17-hydroxylated derivatives are also released in small amounts. Plasma levels of testosterone in males are about 0.6 mcg/dL after puberty and appear to decline after age 50. Testosterone is also present in the plasma of women in concentrations of approximately 0.03 mcg/dL and is derived in approximately equal parts from the ovaries and adrenals and by the peripheral conversion of other hormones. 

Dehydroepiandrosterone (DHEA) is a precursor hormone secreted by the adrenal cortex and to a lesser extent by the central nervous system (Chapter 40 The Gonadal Hormones Inhibitors). It is readily converted to androstenedione, testosterone, and androsterone. In peripheral tissues, aromatase converts DHEA to estradiol. In the plasma, DHEA is converted to DHEA sulfate (DHEAS). 

It has been shown that hormones are not exclusive products of the glands but are also formed in metabolizing organs. These hormones, however, contrary to the classical hormones, are not secreted into the blood. It has been established that testosterone formed in the liver from androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate does not enter the blood [305,323,388]. It has also been established that secreted and metabolically produced testosterone do not have the same metabolism [169, 311]. 

Furthermore Tait and co-workers [322] pointed out the marked difference in the urinary and blood production rates of testosterone obtained in women after injection of radioactive testosterone. He concluded that steroids produced from dehydroepiandrosterone contribute little to the blood production rate of androstenedione and testosterone in normal subjects [403]. According to Tait [324], all the blood production rate of androstenedione in the female and testosterone in the male is due to the same secreted steroid, while the blood production rate of testosterone in the female and androstenedione in the male is due about one-half to the same secreted steroid and one-half to converted precursor. The normal male secretes a ratio of testosterone to androstenedione of about 10 1 and the normal female secretes a ratio of androstenedione to testosterone of about 25 1. 

Testosterone is primarily produced by the interstitial ceils ihetestes,. synthesized largely from cholesterol made in leitoli cells. DHT is also secreted by the testes, as well as hang produced in other tissues. Tlie ovaries and adrenal AOc.xsynlhesizx androstenedione and DHEA. which can be... 

Figure 50-8 The regulatory feedback loop of the hypothalamic-pituitary-adrenal axis. CRH under the influence of neural factors and other modifiable factors that control its pulsatile and circadian secretion acts on the pituitary to produce hormone (ACTH). ACTH in turn stimulates the adrenal gland to form cortisol, aldosterone, dehydroepiandrosterone (DHEA), and androstenedione. Corticosteroids and gamma amino butyric acid (GABA) are inhibitory to CRH and ACTH release, and AVP stimulates ACTH release.

The adrenal cortex also secretes small quantities of the estrogenic steroids (Cis steroids)." However, 17P-estradiol and estrone are largely derived from the gonads and from peripheral conversion of testosterone and androstenedione by the aromatase enzyme located in other tissues, such as fat and the liver. 

Age and familial factors in both men and women influence both plasma adrenal androgens (DHEA and DHEA-S). Adrenal androgen secretion starts to rise about the age of 9, peaks at about age 25, and declines after age 30. In the seventh decade of fife, the adrenal androgen concentrations fall to prepubertal concentrations. Thus in the elderly, the circadian variation in plasma DHEA is relatively blunted and dissociated from the circadian variation in cortisol. The adrenal contribution of serum androstenedione declines with age. DHEA and DHEA-S responses to stimulation with exogenous ACTH are... 

The responses of adrenal androgen secretion to ACTH stimulation are variable. Plasma DHEA and androstenedione increase threefold to fourfold after 90 minutes of stimulation with ACTH (i0 lg/m ). DHEA-S, on the other hand, increases 30% to 50% with ACTH administration. ACTH stimulation studies are not considered useful in evaluating hypoandrogenic disorders. 

Concentrations of androstenedione, DHEA, and DHEA-S begin to increase as early as 6 to 7 years of age, several years before maturation of the hypothalamic-pituitary-gonadal axis. The onset of puberty is associated with nocturnal surges in LH and, to a lesser extent, FSH secretion. The overall changes associated with puberty reflect the theory that the hypothalamic-pituitary system becomes less sensitive to feedback inhibition by circulating androgens, resulting in... 

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