Steroidogenic Enzymes

Abstract

The enzymes and pathways of steroidogenesis are familiar to most endocrinologists, but the biochemistry and molecular biology of these processes are still being studied. This chapter outlines current knowledge about each enzyme. The quantitative regulation of steroidogenesis occurs at the first step, the conversion of cholesterol to pregnenolone. Chronic regulation is principally at the level of transcription of the gene for P450 side chain cleave (P450scc), which is the enzymatically rate-limiting step. Acute regulation is mediated by steroidogenic acute regulatory protein, which facilitates the rapid influx of cholesterol into mitochondria, where P450scc resides. Qualitative regulation, determining the class of steroid produced, is principally determined by P450c17. In the absence of P450c17 in the zona glomerulosa, C21 deoxy steroids are produced, leading to the mineralocorticoid aldosterone. In the presence of the 17alpha-hydroxylase but not the 17,20 lyase activity of P450c17 in the zona fasciculata, C21, 17-hydroxy steroids are produced, leading to the glucocorticoid cortisol. When both the 17alpha-hydroxylase and 17,20 lyase activities of P450c17 are present in the zona reticularis, the androgen precursor dehydroepiandrosterone is produced. The discrimination between 17alpha-hydroxylase and 17,20 lyase activities is regulated by two posttranslational events, the serine phosphorylation of P450c17 and the allosteric action of cytochrome b5, both of which act to optimize the interaction of P450c17 with its obligatory electron donor, P450 oxidoreductase.

Colon cancer cells produce immunoregulatory glucocorticoids

“…Most of these enzymes are transcriptionally regulated by tissue-specific nuclear receptors, such as LRH-1 in the intestine (Miller, 2008). We thus examined the expression of LRH-1 and different steroidogenic enzymes required for GC synthesis in various established CRC cell lines by reverse transcription-PCR.…”

“…The synthesis of GC from cholesterol involves a series of enzymatic steps catalyzed by steroidogenic enzymes of the cytochrome P450 (CYP) and the hydroxysteroid dehydrogenase family (Miller, 2008). In the intestine, steroidogenesis is critically regulated by the nuclear receptor and transcription factor liver receptor homolog-1 (LRH-1, NR5A2; Mueller et al, 2006Mueller et al, , 2007Coste et al, 2007).…”

Insulin and hyperandrogenism in women with polycystic ovary syndrome

“…In humans, the inner parts of the adrenal cortex (zona fasciculata and zona reticularis) produce androgen such as DHEA and androstenedione. The zona fasciculata is relatively less efficient in producing androgen and thus secretes mainly glucocorticoids, namely cortisol [19,20]. The most potent stimulus of adrenocortical cells is unquestionably the adrenocorticotropin hormone (ACTH), which induces a substantial increase in all steroids, both in vivo and in vitro conditions [21].…”

Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1

“…Steroid hormones are synthesized from cholesterol, which is delivered to the inner compartments of mitochondria by steroidogenic acute regulatory protein (StAR) (Papadopoulos and Miller, 2012;Stocco, 1997Stocco, , 2000. Cholesterol is converted to pregnenolone by P450 side chain cleavage enzyme (P450scc/CYP11A1/Cyp11a1), a rate-limiting enzyme in the synthesis of all steroid hormones (Miller, 2008;Papadopoulos and Miller, 2012). Thereafter, tissue-specific P450 hydroxylases and hydroxysteroid dehydrogenases catalyze reactions that produce tissue-specific steroid hormones (Miller, 1988(Miller, , 2008Miller and Auchus, 2011).…”