Steroid biosynthesis

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

Crucial Role Reported for TSPO in Viability and Steroidogenesis is a Misconception. Commentary: Conditional Steroidogenic Cell-Targeted Deletion of TSPO Unveils a Crucial Role in Viability and Hormone-Dependent Steroid Formation.

Abstract: Recent reports on Leydig cell-specific Tspo conditional knockout TspocΔ/Δ mice (1), viable global Tspo knockout (Tspo−/−) mice from two independent laboratories (2, 3), and clones of CRISPR/Cas9-mediated Tspo-deleted MA-10 Leydig cells (MA-10TspoΔ/Δ) (4) established that TSPO is not essential for steroid hormone biosynthesis or viability [reviewed in Ref. (5, 6)]. These reports refuted 25 years of dogma that described TSPO as a mitochondrial cholesterol transport protein, indispensable for steroidogenesis. In response, the research group involved in most of the early studies linking TSPO and steroidogenesis investigated Leydig cell-specific and adrenocortical cell-specific TspocΔ/Δ mice (7) and presented results that seem to repudiate the recent findings and revive the old model. In this commentary, we would like to point out that interpretations made in the manuscript by Fan et al. (7) are seriously flawed.

The intermediary role of 5-pregnene-3β,20β-diol in the biosynthesis of 16-unsaturated C19 steroids in boar testis

Abstract: 1. The possible involvement of 5-pregnene-3beta,20beta-diol in 16-unsaturated C(19) steroid biosynthesis has been investigated. 2. 5,16-Androstadien-3beta-ol (andien-beta) formation from [4-(14)C]pregnenolone (3beta-hydroxy-5-pregnen-20-one), 5-pregnene-3beta,20alpha-diol and 5-pregnene-3beta,20beta-diol was studied in homogenates of boar testis and the mean yields obtained were 25.6, 2.7 and 16.0% respectively. 3. Short-term kinetic studies with pregnenolone and 5-pregnene-3beta,20beta-diol separately and together suggested that the latter compound might be an intermediate in the biosynthesis of andien-beta. 4. In agreement with this interpretation, radioactive 5-pregnene-3beta,20beta-diol has been isolated during andien-beta biosynthesis from [4-(14)C]pregnenolone in the presence of NADPH, more radioactivity being trapped under limiting conditions of andien-beta formation with NADH present as cofactor. 5. Further, 5-pregnene-3beta,20beta-diol and andien-beta have been shown to inhibit the formation of the 16-unsaturated C(19) steroid from [4-(14)C]pregnenolone, the yield of radioactive 5-pregnene-3beta,20beta-diol increasing in the presence of added unlabelled andien-beta. 6. It is concluded that there may be two pathways leading to 16-unsaturated C(19) steroid formation from pregnenolone, one of these involving 5-pregnene-3beta,20beta-diol as an intermediate. Possible mechanisms are presented and discussed.

Met-Enkephalin Inhibits Mineralocorticoid Production in Isolated Human Aldosteronoma Cells

Abstract: In vitro application of the morphinomimetic met-enkephalin resulted in inhibition of mineralocorticoid production by aldosterone-producing adenomas. Aldosterone, deoxycorticosterone, and corticosterone production by adrenocortical cells isolated from aldosteronomas has been studied under basal conditions and after stimulation with ACTH-(1-24). The blocking effect of met-enkephalin on the rate of aldosterone, deoxycorticosterone, and corticosterone release was significant at a concentration as low as 10(-11) M (P less than 0.001, P less than 0.01, and P less than 0.001, respectively). Dose-dependent inhibition of steroid biosynthesis became more apparent with increasing amounts of met-enkephalin in the incubation medium (10(-11)-10(-5) M); at a concentration of 10(-5) M, met-enkephalin decreased the production of aldosterone by 45%, that of deoxycorticosterone by 51%, and that of corticosterone by 44%. Increased steroid biosynthesis stimulated by ACTH-(1-24) was also significantly blocked by met-enkephalin. In a concentration of 10(-5) M, met-enkephalin produced significant decreases in aldosterone (P less than 0.001), deoxycorticosterone (P less than 0.05), and corticosterone (P less than 0.001) production compared to the peak values obtained after stimulation with 0.85 X 10(-10) M ACTH-(1-24). These data allow us to conclude that the inhibitory effect of met-enkephalin on mineralocorticoid production exerted at the level of the adrenals might be complementary to the factor(s) thought to be involved in the regulation of adrenal steroid production, playing a role similar to that of the biogenic amines originating in the adrenal medulla and regulating the adrenal cortex by a peripheral neurohumoral paracrine mechanism.

Angiotensin II receptors of human and primate adrenal fasciculata and glomerulosa: correlations of binding and steroidogenesis.

Abstract: Subcellular fraction and collagenase-dispersed isolated adrenal fasciculata and glomerulosa cells from human and primate adrenal glands and cortisol-producing tumors have been utilized to study angiotensin II (Ang II) receptors and steroid biosynthesis. The receptor density of glomerulosa was threefold higher than that of fasciculata. A benign cortisol-producing adenoma did not differ from normal fasciculata, but a malignant tumor had significantly lower affinity binding. Agonist and antagonist analogues of Ang II competed for binding sites commensurate with known biologic activity. The Kd of binding to fasciculata (2 nmol/L) correlated well with the ED50 of cortisol biosynthesis in normal and adenomatous tissue. Analogue binding also had corresponding changes in cortisol biosynthesis. The ED50 for aldosterone biosynthesis by glomerulosa cells was significantly lower at 55 pmol/L. Fewer receptors in human fasciculata as compared to glomerulosa and a less sensitive response to Ang II are consistent with previous in vitro observations in other species. These studies suggest that there may be a biologically relevant Ang II receptor of human and primate adrenal fasciculata that share many characteristics with the receptor of the glomerulosa.