Steroid biosynthesis

About: Steroid biosynthesis is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 58977 citations.

Interleukin-1α and -β modulation of luteinized human granulosa cell oestrogen and progesterone biosynthesis

Abstract: This study was designed to test the hypothesis that interleukin-1 alpha (IL-1 alpha) and beta directly affect progesterone, and oestradiol production in cultures of purified human granulosa cells. Luteinized granulosa cells were obtained from women during in-vitro fertilization cycles. Granulosa cells with and without associated white blood cells were cultured in the presence of IL-1 alpha and IL-1 beta (0.5-50 ng/ml) for 48 h. Media were changed at 24 h intervals and assayed for progesterone and oestradiol. In separate experiments, granulosa cell viability was assessed with the tetrazolium salt reduction assay, haemocytometer cell counts, and Trypan blue dye exclusion. Our results indicate that progesterone synthesis by basal and human chorionic gonadotrophin (HCG)-stimulated granulosa cells co-cultured with white blood cells was inhibited by 5.0 ng/ml of IL-1 alpha and IL-1 beta at 48 h of culture. In the presence of white blood cells, granulosa cell oestradiol synthesis was inhibited by IL-1 beta but not IL-1 alpha. Oestradiol was inhibited after both 24 and 48 h of culture and was maximally affected by 5.0 ng/ml of IL-1 beta. In contrast, basal and HCG-stimulated oestradiol production by granulosa cells cultured free of white blood cells was inhibited only by IL-1 alpha. IL-1 alpha at 5.0 ng/ml produced maximal inhibition of basal oestradiol (57%) and HCG-stimulated oestradiol (41%) production at 48 h of culture. Gonadal steroid inhibition by IL-1 alpha and IL-1 beta was not mediated through cytotoxic or antiproliferative effects on granulosa cells. Specificity of the granulosa cell response to IL-1 alpha and IL-1 beta was demonstrated by abrogation of steroid inhibition with anti-IL-1 alpha and IL-1 beta neutralizing antibodies. In conclusion, IL-1 alpha directly inhibited the production of oestradiol by human ovarian granulosa cells. IL-1 alpha and IL-1 beta also exerted indirect effects on steroid production via white blood cells that are usually present in granulosa cell cultures if steps are not taken to remove them. These data support the hypothesis that cytokines play an important role in intra-ovarian regulation of steroid biosynthesis.

Functional gains in energy and cell metabolism after TSPO gene insertion.

Abstract: Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions. To examine whether overexpression of the TSPO protein alters the cellular bioenergetic profile, Jurkat cells with low to absent endogenous expression were transfected with a TSPO construct to create a stable cell line with de novo expression of exogenous TSPO protein. Expression of TSPO was confirmed by RT-qPCR, radioligand binding with [3H]PK11195 and immunocytochemistry with a TSPO antibody. We demonstrate that TSPO gene insertion causes increased transcription of genes involved in the mitochondrial electron transport chain. Furthermore, TSPO insertion increased mitochondrial ATP production as well as cell excitability, reflected in a decrease in patch clamp recorded rectified K channel currents. These functional changes were accompanied by an increase in cell proliferation and motility, which were inhibited by PK11195, a selective ligand for TSPO. We suggest that TSPO may serve a range of functions that can be viewed as downstream regulatory effects of its primary, evolutionary conserved role in cell metabolism and energy production.

eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia

Abstract: Nitric oxide (NO) plays a role in a wide range of physiological processes. Aside from its widely studied function in the regulation of vascular function, NO has been shown to impact steroidogenesis in a number of different tissues. The goal of this review is to explore the effects of NO on steroid production and further, to discern its source(s) and mechanism of action. Attention will be given to the regulation of NO synthases in specific endocrine tissues including ovaries, testes, and adrenal glands. The effects of hypoxia on generation of NO and subsequent effects on steroid biosynthesis will also be examined. Finally, a potential model for the interaction of hypoxia on NO synthesis and steroid production is proposed.