Multiple Signaling Pathways Regulating Steroidogenesis and Steroidogenic Acute Regulatory Protein Expression: More Complicated than We Thought

Abstract

Steroid hormone biosynthesis in steroidogenic cells is regulated through trophic hormone activation of protein kinase A (PKA) signaling pathways. However, many examples of the regulation of steroid synthesis via pathways other than the PKA pathway have been documented. In some cases these pathways act independently of PKA activation whereas in other cases, they act synergistically with it. The current understanding of additional signaling pathways and factors, such as the protein kinase C pathway, arachidonic acid metabolites, growth factors, chloride ion, the calcium messenger system, and others capable of regulating/modulating steroid hormone biosynthesis, and in many cases steroidogenic acute regulatory protein expression, are discussed in this review.

Effects of fluorotelomer alcohol 8:2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade

“…This result is consistent with those of the previous study reporting that a 50% decrease in cellular cAMP level significantly reduced aldosterone production by approximately 75% in bovine adrenal glomerulosa cells treated with atrial natriuretic peptide (ANP) (MacFarland et al, 1991). Adenylate cyclase is the enzyme responsible for catalyzing conversion of cellular ATP to cAMP via a G-protein-coupled receptor pathway (Stocco et al, 2005). In the present study, the decreased basal adenylate cyclase activity and absence of effect on ATP levels suggest that 8:2 FTOH could decrease cellular cAMP by depressing basal adenylate cyclase activity.…”

“…cAMP is an important secondary messenger that stimulates steroid hormone biosynthesis in the human adrenal cortex (Sewer and Watermen, 2001;Stocco et al, 2005). The transcriptional profiles of most steroidogenic genes (e.g., StAR, CYP11A, CYP11B, CYP17 and CYP21) are cAMP-dependent (Sewer and Watermen, 2001).…”

Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats

“…1, reviewed in Payne & Hales, 2004;Stocco et al, 2005). The steroidogenic function of Leydig cell is predominantly regulated by pituitary luteinizing hormone (LH) or its placental counterpart human chorionic gonadotropin (hCG).…”

An arachidonic acid generation/export system involved in the regulation of cholesterol transport in mitochondria of steroidogenic cells

“…It is now well established that there are several hormone-regulated proteins necessary in cyclic 3 0 -5 0 -adenosine monophosphate (cAMP) mediated stimulation of cholesterol availability and particularly in the transport of cholesterol from the outer to the inner mitochondrial membrane. Three of them are mitochondrial proteins: the peripheral benzodiazepine receptor (PBR) [2], the steroidogenic acute regulatory protein (StAR) [3] and the acyl-CoA thioesterase (Acot2) [4][5][6].…”