STUDIES ON REGULATION OF STEROID HORMONE SYNTHESIS AND METABOLISM IN FETO-PLACENTAL UNIT

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We had identified 16-dehydropregnenolone sulfate (16-DHPS) as a novel steroid in serum from neonate. We also revealed that this steroid is synthesized according to the following process : Pregnenolone sulfate (PregS)→16-hydroxy-PregS (16-OH-PregS) →16-DHPS. However, the physiological significance of 16-DHPS is unclear. The aim of this study is to investigate whether this metabolic pathway regulate the known steroid pathway, PregS→17-hydroxy-PregS (17-OH-PregS)→dehydroepiandrosterone sulfate (DHEAS)→16-OH-DHEAS, because these pathways use common substrate, PregS. Firstly, we developed methods for the measurement of these steroids : PregS, 16-OH-PregS, 16-DHPS, 17-OH-PregS, DHEAS and 16-OH-DHEAS by GC/MS. Methods for the measurement of their unconjugated steroids by EIA were also established (Biol. Pharm. Bull. 24,867 (2001). Using these methods, serum concentrations of these steroids were determined in the samples from pregnant women. Key step of the above two pathways is 17-hydroxylation and 16-hydroxylation of Preg(S). 17- and 16-hydroxylase activities were obtained by the ratio of product/substrate concentration that is 17-OH-Preg(S)/Preg(S) ratio and 16-OH-Preg(S)/Preg(S) ratio, respectively. As a result, the 17-hydroxylase activities were decreased according to the course of pregnancy. Inversely, the 16-hydroxylase activities were increased at term compared with those at the first trimester of pregnancy. There were no significant changes of the product/substrate ratios for the other steroids in the above pathway. Present data suggest that 17-hydroxylation of Preg(S) is to be regulated by 16-hydroxylation of Preg(S).