Dehydroepiandrosterone sulfate secretion

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. 

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... 

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).

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]. 

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]. 

The formation of estrone and estradiol in placental tissues come.s principally from fetal dehj droepiandrosterone sulfate. In 1955, Migeon et al. obsei"ved that more dehydroepiandrosterone is present in the umbilical cord blood than in maternal plasma. These results have been confirmed and since, as indicated previously (Section HI, F, 1, a), the concentration of dehydroepiandrosterone sulfate is higher in the umbilical artery than in the umbilical vein, the fetal compartment must secrete dehydroepiandrosterone sulfatt to the placental compartment. 

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... 

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