Steroid biosynthesis

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

Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria.

Abstract: Mitochondrial cytochrome P450 systems are an indispensable component of mammalian steroid biosynthesis; they catalyze regio- and stereo-specific steroid hydroxylations and consist of three protein entities: adrenodoxin reductase (AdR), adrenodoxin (Adx), and a mitochondrial cytochrome P450 enzyme, e.g., CYP11A1 (P450 side chain cleavage, P450scc). It is known that the latter two are able to generate reactive oxygen species (ROS) in vitro . In this study, we investigated whether this ROS generation also occurs in vivo and, if so, whether it leads to the induction of apoptosis. We found that overexpression of either human or bovine Adx causes a significant loss of viability in 11 different cell lines. This loss of viability does not depend on the presence of the tumor suppressor protein p53. Transient overexpression of human Adx in HCT116 cells leads to ROS production, to a disruption of the mitochondrial transmembrane potential (DeltaPsi), to cytochrome c release from the mitochondria, and to caspase activation. In contrast, the effect of transient overexpression of human CYP11A1 on cell viability varies in different cell lines, with some being sensitive and others not. We conclude that mitochondrial cytochrome P450 systems are a source of mitochondrial ROS production and can play a role in the induction of mitochondrial apoptosis.

Endothelial nitric oxide synthase activation and nitric oxide function: new light through old windows.

Abstract: The principle mechanisms operating at the level of endothelial nitric oxide synthase (eNOS) itself to control its activity are phosphorylation, the auto-regulatory properties of the protein itself, and Ca(2)(+)/calmodulin binding. It is now clear that activation of eNOS is greatest when phosphorylation of certain serine and threonine residues is accompanied by elevation of cytosolic [Ca2+](i). While eNOS also contains an autoinhibitory loop, Rafikov et al. (2011) present the evidence for a newly identified 'flexible arm' that operates in response to redox state. Boeldt et al. (2011) also review the evidence that changes in the nature of endothelial Ca(2)(+) signaling itself in different physiologic states can extend both the amplitude and duration of NO output, and a failure to change these responses in pregnancy is associated with preeclampsia. The change in Ca(2)(+) signaling is mediated through altering capacitative entry mechanisms inherent in the cell, and so many agonist responses using this mechanism are altered. The term 'adaptive cell signaling' is also introduced for the first time to describe this phenomenon. Finally NO is classically regarded as a regulator of vascular function, but NO has other actions. One proposed role is regulation of steroid biosynthesis but the physiologic relevance was unclear. Ducsay & Myers (2011) now present new evidence that NO may provide the adrenal with a mechanism to regulate cortisol output according to exposure to hypoxia. One thing all three of these reviews show is that even after several decades of study into NO biosynthesis and function, there are clearly still many things left to discover.

Role of follicle wall in meiosis reinitiation induced by insulin in Rana pipiens oocytes.

Abstract: The involvement of the ovarian follicle wall in insulin induction of Rana pipiens oocyte maturation in vitro was examined. Complete removal of the follicle wall significantly decreased, but did not obliterate, oocyte maturation (i.e., germinal vesicle breakdown, GVBD) induced by insulin. Dose-response studies of GVBD induction revealed that oocytes within intact follicles were at least 100 times more sensitive to insulin than denuded oocytes. Addition of cyanoketone, a steroid biosynthesis inhibitor, to intact follicles also suppressed insulin-induced GVBD. Inhibitory effects of either follicle wall removal or cyanoketone were not observed when denuded oocytes were treated with progesterone. Addition of either progesterone or pregnenolone to insulin-treated denuded oocytes augmented the oocyte GVBD response compared to either steroid alone and essentially replaced the effect of the follicle wall. In summary, steroidogenesis in the follicle wall appears to be a major factor contributing to the ability of insulin to induce GVBD. However, whether insulin stimulates follicle wall steroidogenesis or simply augments the biological activity of endogenous basal steroid levels is unresolved. The in vitro results show that oocyte maturation can be modulated by the combined actions of several hormones. Such steroid-insulin interactions may also be relevant to understanding the control of oocyte maturation in amphibians and other vertebrates, including mammals, under physiological conditions in vivo.

Time Course of Steroid Biosynthesis and Metabolism in Haplopappus heterophyllus

Abstract: A single dose of mevalonic acid-2-14C was administered simultaneously to 6 Haplopappus heterophyllus plants. They were harvested at intervals ranging from 3 days to 6 months. Four groups of biosynthetically related sterols were found to be radioactive in each plant, and the changes in radioactivity with time were studied. The most striking finding was a radioactive phenolic material present only in the 6-month plant, which had flowered.

Synthesis of new molecular probes for investigation of steroid biosynthesis induced by selective interaction with peripheral type benzodiazepine receptors (PBR).

Abstract: In the present study, we have synthesized and tested novel pyridopyrrolo- and pyrrolobenzoxazepine derivatives, as novel and selective peripheral type benzodiazepine receptor (PBR) ligands, and their ability to modulate steroid biosynthesis has been investigated. A subset of new ligands bind the PBR (rat brain and testis) with picomolar affinity, representing the most potent ligands that have been identified to date, and elicited effects on endogenous rate of steroidogenesis in MA10 Leydig cells, having similar potency and effect as PK11195. Several compounds, differently substituted at C-7, were used as molecular yardsticks to probe the spatial dimension of the lipophilic pocket L4 in the receptor binding site.