Pregnenolone

About: Pregnenolone is a research topic. Over the lifetime, 3539 publications have been published within this topic receiving 126444 citations. The topic is also known as: (3b)-3-hydroxy-Pregn-5-en-20-one & 3-Hydroxypregn-5-en-20-one.

A Study of a Pregnancy with Low Estrogen Production Due to Placental Sulfatase Deficiency

Abstract: A pregnancy has been investigated in which maternal urinary excretion of estrogens was abnormally low. The excretion of estrone, estradiol and estriol was, respectively, 15%, 15% and 5% of levels found in normal pregnancy. Urinary pregnanediol excretion was within the normal range. There was no evidence of either fetal abnormality or growth retardation. A normal male baby was delivered by cesarian section at 39 weeks gestation. Both in vivo and in vitro the placenta was shown to have a normal potential for metabolism of 3β-hydroxy-androst-5-en- 17-one (DHEA) to estrogens, but lacked ability to hydrolyze androst-5-en-17-one-3β-yl sulfate (DHEAS). In vitro incubation experiments with the substrates pregnenolone-7-3H sulfate, estrone- 4-14C sulfate and nitrocatechol sulfate indicated that the placenta was also deficient in sulfatase activity with respect to these substrates. Cord plasma levels of l6α-hydroxyandrost-5-en-17-one- 3β-yl sulfate (160HDHEAS) and pregn-5-en-2O-one-3β-yl sulfate (PS) were in the ra...

The effects of hydrogen peroxide on steroidogenesis in mouse Leydig tumor cells

Abstract: It has previously been reported that treatment of rat luteal cells and human granulosa luteal cells with hydrogen peroxide (H2O2) results in a significant inhibition of steroid production. The mechanism of inhibition in the former was found to be at the level of cholesterol transport into the mitochondria, whereas in the latter it was found to be a result of inhibition of one or more enzymes in the steroidogenic pathway. In the present study we examined the effects of H2O2 on hormone-stimulated steroid production in another steroidogenic cell type, the Leydig cell. Our results demonstrate that treatment of either LH- or cAMP analog [(Bu)2cAMP]-stimulated MA-10 mouse Leydig tumor cells with H2O2 results in a dose-dependent inhibition of the production of progesterone (the major steroid produced in MA-10 cells). It was also observed that similar concentrations of H2O2 resulted in a significant inhibition of protein synthesis, a finding which could in part be responsible for the observed decrease in steroid production. Furthermore, although H2O2 resulted in a dose-dependent inhibition of (Bu)2cAMP-stimulated pregnenolone production, addition of the hydroxylated intermediate 22R-hydroxycholesterol and inhibitors of further pregnenolone metabolism demonstrated that cholesterol side-chain cleavage complex activity was unaffected by H2O2. Conversely, incubation of H2O2-treated cells in the presence of pregnenolone resulted in a very significant inhibition of progesterone synthesis. These data indicate that H2O2 inhibits steroidogenesis in Leydig tumor cells primarily by inhibiting the activity of the 3 beta-hydroxysteroid dehydrogenase, but that other effects of H2O2 such as inhibition of protein synthesis and the transfer of cholesterol to the cholesterol side-chain cleavage complex may also be involved.