Dehydroepiandrosterone secretion

Dehydroepiandrostemne (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are the most abundant steroids secreted by the adrenal cortex under pituitary ACTH control (B5). Very little plasma DHEA(S) appears to be of testicular or ovarian origin. Physiologically, the concentration of DHEA(S) in the blood oscillates coincidentally with cortisol, consistent with the response of adrenal... 

Chemically, androstenol and dehydroepiandrosterone sulfate, found in male axillary secretion (Brooksbank etal, 1974), occur in active samples. Aliphatic acids with 2 to 18 carbon members may also contribute to the axillary odor (Preti etal, 1987). 

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. 

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). 

The adrenal glands play an important role in pubertal development. Termed adrenarche, the maturation of a prominent zona reticularis, the innermost layer of the cortex, begins around age six to eight in girls, resulting in increased secretion of the adrenal androgens, dehydroepiandrosterone (DHEA) and DHEA sulfate (Beckman Feuston, 2003). The rise in these hormones leads to the development of pubic and axillary hair. Recent evidence suggests... 

Fig. 10. Hypothesis for the interaction of the A-kinase (A-K) system activated by ACTH with the C-kinase system (C-K) in the long-term regulation of the enzymes of steroidogenesis throughout the adrenal cortex. The primary determinant of zonation of A-kinase and C-kinase activities, via zonation of cell surface receptors or other mechanisms, is hypothesized to be a gradient (e.g., of steroids) created by the pattern of blood flow in the adrenal cortex. The resultant levels of induction of steroidogenic enzymes are indicated by to show particular elevation and by to show particular lack of induction or suppression of induction. Other enzymes involved in steroidogenesis are shown in parentheses. SCC=cholesterol side-chain cleavage enzyme 3/3=3/3-hydroxysteroid dehydrogenase 17a=17a-hy-droxylase 21 =21-hydroxylase 11/3= 11/3-hydroxylase CMO= corticosterone methyl oxidase activity of 11/3-hydroxylase. Secreted steroids are indicated as B=corticosterone Aldo=aldosterone F=cortisol DHEA(S)= dehydroepiandrosterone (sulfate).

I) Consider three structurally similar Cis steroids —testosterone, an-drostenedione, and dehydroepiandrosterone. Each of these compounds is secreted into the blood stream by glands, and after provoking its biochemical effect, is metabolized and excreted. If the only source of the plasma pool were provided by the glandular secretion of the hormone, then the secretion rate would be used to calculate the plasma concentration. However, the picture in the case of the three Ci steroids is complicated by the fact that the three compounds are peripherally interconvertible. Since both glandular secretion and peripheral conversion of precursors contribute to the plasma pool, the production rate is used to... 

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. 

According to the classical view of metabolism the hormones are synthesized as free steroids in endocrine tissues and prepared for excretion in urine by peripheral metabolism and conjugation. This view had to be modified upon the isolation of dehydroepiandrosterone sulfate from adrenal tumor [307]. Thus dehydroepiandrosterone sulfate, a steroid conjugate, was shown to be secreted by the adrenal tissue. Isotopic methods also pointed in the same direction. Lieberman et al. [304], using... 

However, the validity of the model used by Gurpide el al. [174,175, 176,306] for the determination of the secretion and interconversion of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstene-dione, and testosterone was criticized by Baulieu et al. [404] and Migeon etal. [405]. 

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.

Testosterone and oestradiol are known as the sex steroid hormones. Testosterone is the principal androgen and is synthesized by the testes in the male. Oestradiol. which is secreted by the ovaries, varies w idely in concentration in plasma throughout the female menstrual cycle. Steroids with oestradiol-like action arecalledoestrogens. Progesterone is a product ofthe ovary and is secreted when a corpus lutcum forms after ovulation. Normal female plasma also contains testosterone, about half of which comes from the ovary and half from peripheral conversion of androstenedione and dehydroepiandrosterone (DHA) sulphate which are secreted by the adrenal cortex. Some oestradiol is present in low concentration in normal male plasma. 

As shown in Figure 5.3, pregnenolone (I) is oxidised to progesterone (II) and thence converted via 17a-hydroxyprogesterone (III) into testosterone (V). Testosterone is the most active of the naturally occurring androgens [9, 10]. Androstenedione (VI) and dehydroepiandrosterone (DHA) (IV) form less potent but quantitatively more significant secretion products. 

The development of the various adrenal enzymes in the fetal adrenal may also be of considerable significance in interpreting the lack of activity observed after birth. jS-Hydroxysteroid dehydrogenase is low in fetal liver thus, the pathway prevails (pregnenolone— dehydroepiandrosterone), and cortisol synthesis is low. The relatively large adrenals found in utero may result from compensatory hyperplasia in response to low cortisol secretion. In early embryonic life, 21- and 11-hydroxylase activities are low, but they increase with the age of the fetus. 

The discovery of dehydroepiandrosterone sulfate secretion gave a new incentive to the whole study of conjugation, and it soon became evident that dehydroepiandrosterone sulfate could not only be biosynthesized from sulfo conjugated percursors along a direct biosynthetic pathway, but could also undergo further metabolism, with or without hydrolysis of the sulfate moiety (i.e., indirect or direct metabolism) and act as a privileged precursor of active steroids. 

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