Prohibitin-1 is an ACTH-Regulated Protein in Human and Mouse Adrenocortical Cells and Plays a Role in Corticosteroid Production

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Authors

  • Suresh Mishra
     Department of Internal Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3P4 ,CA
  • Simarjit Kaur Sidhu
     1Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, R3E 3P4 ,CA
  • Geetika Bassi
     Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, R3E 3P4 ,CA

DOI:

https://doi.org/10.18311/jer/2023/34993

Keywords:

Adrenal Cortex, Adrenocorticotrophic Hormone, Cholesterol, Corticosterone, Mitochondria

Abstract

Cell-intrinsic early events involved in different trophic hormone-induced steroidogenesis in their respective steroidogenic cell type are very similar. For example, the activation of the cAMP-PKA signaling pathway in response to trophic hormone stimulation and, subsequently, cholesterol transport to the mitochondria to initiate steroidogenesis is common to them. Recently, we have found that an evolutionarily conserved protein, prohibitin-1 (PHB1), is regulated by Luteinizing Hormone (LH) in murine Leydig cells and plays a role in interconnected cell signaling and mitochondrial steps pertaining to testosterone production. Among the primary steroidogenic tissues, PHB1 expression levels are highest in the adrenal cortex (The Human Protein Atlas); however, its regulation and role in adrenocortical cells are virtually unknown. We investigated the regulation and the role of PHB1 in adrenocortical cells in vitro using human HAC15 and mouse Y-1 cell culture models. It was found that Adrenocorticotrophic Hormone (ACTH) stimulation upregulates PHB1 levels in adrenocortical cells in a time-dependent manner. A similar effect on PHB1 levels was also observed in response to dibutyryl-cAMP stimulation, a cell-permeable analogue of cAMP (the second messenger for ACTH action). Moreover, manipulating PHB1 levels in adrenocortical cells affected mitochondria, lysosomes, and lipid droplet characteristics, modulated phospho-PKA and phospho-ERK1/2 levels, and altered corticosteroid production. This finding suggests that ACTH regulates PHB1 in adrenocortical cells and plays a role in corticosteroid production, which was previously unknown.

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Published

2023-09-12

How to Cite

Mishra, S., Sidhu, S. K., & Bassi, G. (2023). Prohibitin-1 is an ACTH-Regulated Protein in Human and Mouse Adrenocortical Cells and Plays a Role in Corticosteroid Production. Journal of Endocrinology and Reproduction, 27(3), 199–210. https://doi.org/10.18311/jer/2023/34993

Issue

Volume 27, Issue 3, September 2023

Section

Research Article Presented at SRBCE 2023
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