Steroid biosynthesis

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

Steroid Biosynthesis by Human Ovarian Granulosa and Thecal Cells

Abstract: The separation of granulosa cells from thecal elements of the human ovarian follicle has been described. The 2 cell types were incubated in vitro with progesterone-4-14C and pregnenolone-7-3H. Steroid metabolites were isolated with each of the cell types and crystallized to constant specific activity. In the granulosa experiment, pregnenolone-7-3H was converted to progesterone, 17-hydroxyprogesterone and estrone, and progesterone-4-14C was converted to 17-hydroxyprogesterone and estrone. In the theca experiment pregnenolone-7-3H was converted to progesterone, 17-hydroxyprogesterone, androstenedione and estradiol, and progesterone-4-14C was converted to the last 3 compounds. The conversion of pregnenolone to progesterone was much more active with the granulosa than the theca, while indications of an alternate pathway via Δ5 compounds were more apparent with thecal cells.

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

Abstract: The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus The human placenta forms at the interface of maternal and fetal circulation It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment This review outlines the mechanisms of human placental handling of steroid compounds Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1 Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1) Maternal-fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1 This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored The structure and the cellular composition of the human placental barrier are introduced While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes With regard to placental structure and function, significant differences exist between species To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory

Diazepam binding inhibitor is a paracrine/autocrine regulator of Leydig cell proliferation and steroidogenesis: action via peripheral-type benzodiazepine receptor and independent mechanisms

Abstract: Previous studies demonstrated that the polypeptide diazepam binding inhibitor (DBI) and its receptor, the peripheral-type benzodiazepine receptor (PBR), are involved in the regulation of steroid biosynthesis and that one site of PBR action resides in mitochondria. In the present investigation, evidence is presented that a functional form of PBR is also present at the cell surface. First, PBR was immunolocalized in the rat testis using biotin-streptavidin peroxidase immunocytochemistry, and results revealed that PBR was present exclusively in the interstitial Leydig cells. Next, the distribution of PBR in MA-10 Leydig cells was further examined using confocal microscopy. MA-10 cells were either fixed and immunostained or fixed/permeabilized and immunostained for PBR, followed by generation of confocal microscope optical sections, three-dimensional reconstructions of these sections, and then generation of vertical confocal sections of the three-dimensional reconstruction. In the fixed/unpermeabilized cells, PBR immunostaining at the cell surface was clearly evident, whereas in the fixed/permeabilized cells, intracellular PBR distribution was more robust. These results suggest that the plasma membrane fraction of the receptor could mediate the action of extracellular PBR ligands on Leydig cell function. Next, we examined whether DBI, the naturally occurring PBR ligand, is secreted by testicular cells and whether it could activate the cell surface PBR. Immunolocalization of DBI demonstrated that it was present in both Leydig and Sertoli cells. Further, using an immunoblot assay, we demonstrated that DBI is present in rat testicular interstitial fluid. Metabolic labeling of cultured immature rat Sertoli cells and MA-10 mouse tumor Leydig cells, followed by immunoprecipitation of the secreted proteins with an anti-DBI antiserum, demonstrated that both Leydig and Sertoli cells secrete DBI and could serve as a cell source for the interstitial fluid DBI. Then, we partially purified the DBI present in conditioned medium and interstitial fluid by reverse phase chromatography and demonstrated it to be bioactive, based on displacement of a radiolabeled benzodiazepine (Ro5-4864)-specific ligand for PBR; pronase treatment of different preparations eliminated all bioactivity. We then examined the effects of DBI on Leydig cell function. DBI added to MA-10 cells affected DNA synthesis and cell growth in a biphasic manner; at low concentrations (1 nM), DBI was mitogenic, increasing [3H]thymidine incorporation and cell numbers by 30-40%, while at high concentrations (1 microM), DBI inhibited cell growth (30-40%). Similar effects on cell growth were obtained using the benzodiazepine Ro5-4864.

Linkage of 11 beta-hydroxylase mutations with altered steroid biosynthesis and blood pressure in the Dahl rat.

Abstract: In Dahl salt-hypertension sensitive (S) and resistant (R) strains fed a high NaCI diet, 11β-hydroxylase polymorphisms cosegregate with the adrenal capacity to synthesize 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) and blood pressure. The R rat carries an 11β-hydroxylase allele that: (i) differs from those of 12 other rat strains; (ii) is associated with a uniquely reduced capacity to synthesize 18-OH-DOC; and (iii) encodes 5 amino acid substitutions in the 11β-hydroxylase protein. The robust salt-resistance of the Dahl R rat may be due in part to reduced synthesis of the mineralocorticoid 18-OH-DOC stemming from mutations in the 11β-hydroxylase gene. 11β-hydroxylase, located on rat chromosome 7, is the first candidate gene identified in an animal model in which coding sequence mutations have been linked to the regulation of blood pressure.