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

16-脱氢孕烯醇酮硫酸盐(16-DHPS)是新生儿血清中的一种新的类固醇。我们还揭示了该类固醇的合成过程如下：孕烯醇酮硫酸盐(PregS)→16-羟基-PregS(16-OH-PregS)→16-DHPS。然而，16-DHPs的生理意义尚不清楚。本研究的目的是研究这一代谢途径是否调节已知的类固醇途径，→17-羟基-孕酮(17-OH-孕酮)→脱氢表雄酮硫酸酯(→16-OH-DHEAS)，因为这些途径使用共同的底物。首先，我们建立了孕激素、16-羟基-孕酮、16-二氢呋喃、17-羟基-孕酮、DHEAS和16-OH-DHEAS的GC/MS测定方法。药。胡说八道。24,867(2001)。使用这些方法，在孕妇的样本中测定了这些类固醇的血清浓度。以上两条途径的关键步骤是孕激素的17-羟化和16-羟化(S)。产物/底物浓度的比值，即17-羟基-孕激素(S)/孕激素(S)和16-羟基-孕激素(S)/孕激素(S)的比值分别获得了17-羟基酶和16-羟基酶活性。结果表明，17-羟基酶活性随孕期的延长而降低。相反，16-羟基酶活性在足月时比妊娠早期升高。在上述途径中，其他类固醇的产物/底物比例没有明显变化。目前的数据表明，孕激素(S)的17-羟基化可能受孕激素(S)的16-羟基化调控。

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).