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Extraadrenal Formation of a Mineralocorticosteroid: Deoxycorticosterone and Deoxycorticosterone Sulfate Biosynthesis and Metabolism^*

Cecil H. and Ida Green Center for Reproductive Biology Sciences, and Departments of Biochemistry and Obstetrics and Gynecology, The University of Texas Southwestern Medical School Dallas, Texas 75235

Correspondence: Address correspondence and requests for reprints to: M. Linette Casey, Ph.D., Cecil H. and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235.

Abstract

EXTRAGLANDULAR steroid hormone formation is now established as a physiological as well as a pathophysiological phenomenon in men, women, and children (1–8). Indeed, it has been demonstrated that most, if not all, estrogen formed in children (9, 10), men (1, 6, 11, 12), and anovulatory (13–15) and postmenopausal (1, 12, 13, 16–21) women arises by the extraglandular aromatization of plasma C₁₉-steroids. Greater than normal extraglandular estrogen formation can give rise to feminization in men (1, 3–6, 8, 9, 22–25) and to uterine bleeding (1, 13–15, 17, 19, 21, 26, 27) and possibly to endometrial carcinoma in women (17, 19, 21, 26). It also is known that the biologically potent androgen testosterone can be produced in extraglandular tissues from circulating precursors (28–33). In fact, most of the testosterone produced in young women arises by this mechanism (28, 29, 31, 32).

In addition to the extraglandular formation of biologically active steroid hormones, it now is known that potent steroid hormones are synthesized from circulating precursors in tissue sites in which the hormone product acts. The classical example of this process is the formation of 5-dihydrotestosterone, the biologically active androgen, from testosterone in androgen-responsive tissues (34). Indeed, deficiencies in steroid 5-reductase activity in androgen-responsive tissues give rise to androgen resistance and, in consequence, male pseudohermaphroditism (35). There are other examples of the in situ formation of biologically active steroid hormones in tissue sites of action, e.g. 17β-estradiol formation from testosterone in the hypothalamus (36), as well as catechol estrogen biosynthesis in this tissue (37).

Footnotes

^* These investigations were supported in part by USPHS Grants 5-P50-HD11149 and 2-P01-AG00306.

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