METABOLISM OF 20β-Hydroxy-4-Pregnen-3-One IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO

Abstract

In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20\g=b\-hydroxysteroid-oxidoreductase which catalyzes the conversion of 20\g=b\-hydroxy-4\x=req-\ pregnen-3-one to progesterone.Since a hepatic 20\g=b\-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20\g=b\-hydroxy-4-pregnen-3-one in these animals.Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20\g=b\-hydroxy-4-pregnen-3-one with uterine tissue: 20\g=b\-hydroxy-5\g=a\-pregnan-3-one, 20\g=b\-hydroxy-5\g=b\-pregnan-3-one, 5\g=a\-pregnane-3\g=a\,20\g=b\-diol,4-pregnene-3\g=a\,20\g=b\-diol and 4-pregnene-3\g=b\,20\g=b\-diol. The conversion of 20\g=b\-hydroxy-4-pregnen-3-one to progesterone permits This work was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungs¬ bereich -Endokrinologie 34. This paper is abstracted from a thesis submitted by M. Holtermann in partial fulfilment of the requirements for the degree of Doctor of Medicine in the Medical School of the University of Hamburg. Trivial names and abbreviations used in the text Progesterone = 4-pregnene-3,20-dione, 17a-hydroxyprogesterone = 17a-hydroxy-4-pregnene-3,20-dione, cortisol = 11/?,17, 21-trihydroxy-4-pregnene-3,20-dione, cortisone = 17,21-dihydroxy-4-pregnene-3,11,20-trione, tetrahydrocortisone = 3a,17,21-trihydroxy-5/?-pregnane-ll,20-dione, /i-cortolone = 3a, 17a,20/5,21-tetrahydroxy-5/?-pregnan-11-one, tK = relative retention time (to chole¬ stane). RGC = radio gas chromatography, GCC = gel column chromatography. TLC = thin-layer chromatography, TMSi = trimethylsilylether, MoTMSi = methoxime-trimethylsilylether.

Relationships of circulating pregnanolone isomers and their polar conjugates to the status of sex, menstrual cycle, and pregnancy

“…Both enzymes show significant activity in the tissues associated with pregnancy (Lisboa & Holtermann 1976, Milewich et al 1979, Sheehan et al 2005; they catalyze the formation of 5a-and 5b-dihydroprogesterone (P5a and P5b) respectively. The subsequent metabolism of dihydroprogesterone epimers to individual PI is catalyzed by stereospecific 3a-or 3b-hydroxysteroid oxidoreductases (Okuda & Okuda 1984, Melcangi et al 1994, Corpechot et al 1997, Ottander et al 2005.…”