Steroid biosynthesis

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

Phenotypic variations in lipoid congenital adrenal hyperplasia.

Abstract: Congenital lipoid adrenal hyperplasia (lipoid CAH) is an autosomal recessive disorder characterized by severe adrenal insufficiency and male sex reversal. Lipoid CAH is caused by mutations in two proteins that are essential for all steroid biosynthesis, the steroidogenic acute regulatory (StAR) protein and cytochrome P450scc. In this review, we discuss the clinical presentation and mechanisms behind the pathology of this fatal disorder.

3β-Hydroxysteroid Dehydrogenase/Δ5→4-Isomerase Activity Associated with the Human 17β-Hydroxysteroid Dehydrogenase Type 2 Isoform1

Abstract: The type 2 isoform of human 17β-hydroxysteroid dehydrogenase (17βHSD2) efficiently catalyzes the oxidative metabolism of androgens and estrogens, and it is expressed in a large series of human peripheral tissues. To obtain a better understanding of the regulation of local steroid biosynthesis and metabolism in human tissues, we have established a dual steroidogenic activity of the 17βHSD2 enzyme after transfection of human 17βHSD2-transfected human embryonic kidney (293) cells. After transient transfection, the metabolism of testosterone, pregnenolone, and dehydroepiandrosterone (DHEA) in intact transfected 293 cells was evaluated by TLC-based radiometric assays. 17βHSD2-transfected cells converted 91% of testosterone (1 μmol/L) into androstenedione in a 2-h incubation period. In addition, pregnenolone (1 μmol/L) was converted to progesterone (18.5%), whereas DHEA (1 μmol/L) was metabolized to androstenedione (8.3% conversion) in a 15-h incubation period. The kinetics of the 3β-hydroxysteroid dehydrogenas...

The role of arachidonic acid on LH-stimulated steroidogenesis and steroidogenic acute regulatory protein accumulation in MA-10 mouse Leydig tumor cells.

Abstract: Metabolic pathways leading to the production of arachidonic acid (AA) and its metabolites have been reported to have modulatory effects on steroidogenesis in a number of cell types. To examine the importance of the arachidonic acid pathway in steroid production and steroidogenic acute regulatory (StAR) protein expression, luteinizing hormones (LH) or N 6-2-o-dibutyryl-adenosine-3∶5-cyclic monophosphate-(Bt2cAMP) stimulated MA-10 mouse Leydig tumor cells were treated with various concentrations of quinacrine (an inhibitor of arachidonic acid production). Incubation of the cells with quinacrine resulted in dose-dependent decreases in steroid production and StAR protein. Twenty micromolars quinacrine inhibited 92 and 91% of LH-induced progesterone and StAR protein, respectively, and 98 and 90% of Bt2cAMP-induced progesterone and StAR protein. Reversal of this inhibition was obtained by incubation of quinacrine-treated cells with various levels of AA, which resulted in a dose-dependent increase in both steroid and StAR protein levels. Two hundred micromolars of AA rescued 57 and 60% of the LH-induced steroid production and StAR protein, respectively, and 52 and 89% of Bt2cAMP-induced steroid production and StAR protein. These results suggest that the effect of AA on LH- and cAMP-stimulated steroidogenesis is associated with the modulation of StAR protein expression.

Functional and Physiological Consequences of StAR Deficiency: Role in Lipoid Congenital Adrenal Hyperplasia

Abstract: The steroidogenic acute regulatory (StAR) protein is essential for all hormone-stimulated steroid biosynthesis. Accordingly, its absence gives rise to the most severe form of congenital adrenal hyperplasia (CAH), lipoid CAH. This life-threatening condition typically manifests itself in the perinatal period. Partial loss-of-function StAR mutations incompletely manifest the condition later in life and are a cause of familial glucocorticoid deficiency type 3. Here, we discuss StAR, its expression pattern and the clinical consequences of the loss of its activity.