Steroid biosynthesis

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

Current knowledge on the acute regulation of steroidogenesis.

Abstract: How rapid induction of steroid hormone biosynthesis occurs in response to trophic hormone stimulation of steroidogenic cells has been a subject of intensive investigation for approximately six decades. A key observation made very early was that acute regulation of steroid biosynthesis required swift and timely synthesis of a new protein whose role appeared to be involved in the delivery of the substrate for all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane where the process of steroidogenesis begins. It was quickly learned that this transfer of cholesterol to the inner mitochondrial membrane was the regulated and rate-limiting step in steroidogenesis. Following this observation, the quest for this putative regulator protein(s) began in earnest in the late 1950s. This review provides a history of this quest, the candidate proteins that arose over the years and facts surrounding their rise or decline. Only two have persisted-translocator protein (TSPO) and the steroidogenic acute regulatory protein (StAR). We present a detailed summary of the work that has been published for each of these two proteins, the specific data that has appeared in support of their role in cholesterol transport and steroidogenesis, and the ensuing observations that have arisen in recent years that have refuted the role of TSPO in this process. We believe that the only viable candidate that has been shown to be indispensable is the StAR protein. Lastly, we provide our view on what may be the most important questions concerning the acute regulation of steroidogenesis that need to be asked in future.

The effects of growth factors and phorbol esters on steroid biosynthesis in isolated human theca interna and granulosa-lutein cells in long term culture.

Abstract: In this report we examined the effects of growth factors and phorbol esters on steroid hydroxylase activity in cultured human thecal and granulosa-lutein cells Treatment of thecal cells with epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF beta), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17 alpha-hydroxylase activity and 17 alpha-hydroxyprogesterone and dehydroepiandrosterone production In contrast, cAMP-stimulated 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity was enhanced by FGF and TGF beta, and treatment with EGF enhanced cAMP-stimulated progesterone production cAMP stimulated 3 beta HSD activity was unaffected by TPA (10 nmol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone production Basal 3 beta HSD activity and progesterone production were inhibited by TPA In contrast to the inhibitory actions of EGF, FGF, and TGF beta on 17 alpha-hydroxylase expression, insulin and insulin-like growth factor-I enhanced forskolin-stimulated 17 alpha-hydroxylase activity In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA TGF beta had no effect on forskolin-stimulated aromatase activity EGF, FGF, and TGF beta did not affect forskolin-stimulated progesterone production, whereas treatment with TPA inhibited cAMP-stimulated progesterone secretion These data suggest that growth factors may differentially regulate cAMP-dependent processes in human thecal and granulosa cells of the developing follicle

Molecular mechanisms of environmental organotin toxicity in mammals.

Abstract: Organotins such as tributyltin are suspected of having multiple toxic effects in mammals, in addition to their endocrine-disrupting function. Endogenous organotin concentrations in human blood range from a few to a few hundred nM. In this review, we summarize recent findings on the mechanisms of toxicity of environmental organotins such as tributyltin (TBT) and triphenyltin (TPT) in mammals. TBT and TPT are potent inhibitors of mitochondrial ATP synthase, and a recent study suggests that TBT binds directly to ATP synthase. Organotins disturb steroid biosynthesis and degradation. TBT and TPT are dual agonists of retinoid X receptor (RXR) and peroxisome proliferator-activated receptor γ (PPARγ); they also induce the differentiation of adipocytes in vitro and in vivo, probably through PPARγ activation, suggesting that they may work as obesogens. Environmental organotins are also neurotoxic; they induce behavioral abnormality and are toxic to the developing central nervous system. In vitro studies have shown that organotins induce intracellular Ca(2+) elevation and glutamate excitotoxicity. Recently, it was reported that endogenous levels of TBT decrease expression of 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA) receptor subunit GluR2, leading to neuronal vulnerability. Most of the experimental studies have employed organotins at concentrations of µM order, and it remains important to clarify the molecular mechanisms of events induced by endogenous levels of environmental organotins.

The seminal vesicle of the African catfish, Clarias gariepinus. A histological, histochemical, enzyme-histochemical, ultrastructural and physiological study.

Abstract: The seminal vesicle of the African catfish, Clarias gariepinus, consists of 36–44 fingerlike lobes built up of tubules in which a fluid is secreted containing acid polysaccharides, acid-, neutral- and basic proteins, and phospholipids. In this fluid sperm cells are stored. The seminal vesicle fluid immobilizes the sperm cells. After ejaculation, it prolongs the period of sperm activity. The seminal vesicle fluid is secreted by the epithelium lining the tubules. The tubules in the proximal part of the lobes are predominantly lined by a simple cylindrical and those of the distal part by a simple squamous epithelium. These epithelial cells contain enzymes involved in energy-liberating processes, the enzyme activites being proportional to the height of the cells. Interstitial cells between the tubules have enzyme-histochemical and ultrastructural features indicative of steroid biosynthesis. Similar characteristics are found in testicular interstitial cells. The most rostral seminal vesicle lobes and the most caudal testicular efferent tubules form a network of tubules that opens at the point where the paired parts of the sperm ducts fuse with each other. The tubules of most seminal vesicle lobes, however, form a complex system that fuses with the unpaired part of the sperm duct.