New insights into signal transduction pathways in adrenal steroidogenesis: role of mitochondrial fusion, lipid mediators, and MAPK phosphatases.

MARIA MERCEDES MORI SEQUEIROS GARCIA ; CRISTINA PAZ ; ANA FERNANDA CASTILLO ; YANINA BENZO ; MATIAS BELLUNO ; ARIANA BALCAZAR MARTINEZ ; PAULA MALOBERTI ; FABIANA CORNEJO MACIEL ; CECILIA PODEROSO

Frontiers in endocrinology

Frontiers in Endocrinology

Año: 2023

Hormone-receptor signal transduction has been extensively studied in adrenalgland. Zona glomerulosa and fasciculata cells are responsible for glucocorticoidand mineralocorticoid synthesis by adrenocorticotropin (ACTH) and angiotensinII (Ang II) stimulation, respectively. Since the rate-limiting step in steroidogenesisoccurs in the mitochondria, these organelles are key players in the process. Themaintenance of functional mitochondria depends on mitochondrial dynamics,which involves at least two opposite events, i.e., mitochondrial fusion and fission.This review presents state-of-the-art data on the role of mitochondrial fusionproteins, such as mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), in Ang IIstimulated steroidogenesis in adrenocortical cells. Both proteins are upregulatedby Ang II, and Mfn2 is strictly necessary for adrenal steroid synthesis. Thesignaling cascades of steroidogenic hormones involve an increase in severallipidic metabolites such as arachidonic acid (AA). In turn, AA metabolizationrenders several eicosanoids released to the extracellular medium able to bindmembrane receptors. This report discusses OXER1, an oxoeicosanoid receptorwhich has recently arisen as a novel participant in adrenocortical hormonestimulated steroidogenesis through its activation by AA-derived 5-oxo-ETE. Thiswork also intends to broaden knowledge of phospho/dephosphorylationrelevance in adrenocortical cells, particularly MAP kinase phosphatases (MKPs)role in steroidogenesis. At least three MKPs participate in steroid production andprocesses such as the cellular cycle, either directly or by means of MAP kinaseregulation. To sum up, this review discusses the emerging role of mitochondrialfusion proteins, OXER1 and MKPs in the regulation of steroid synthesis in adrenalcortex cells.