Related Experiment Video
Updated: Apr 23, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis
Houssein S Abdou1, Francis Bergeron1, Jacques J Tremblay2
1Reproduction, Mother and Child Health, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, Québec, Canada.
Abstract:
Steroid hormones regulate essential physiological processes, and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by luteinizing hormone (LH) via its receptor leading to increased cyclic AMP (cAMP) production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Steroidogenesis then passively decreases with the degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP-to-AMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis, including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutively steroidogenic R2C cells. We have also determined that maximum AMPK activation following stimulation of steroidogenesis in MA-10 Leydig cells occurs when steroid hormone production has reached a plateau. Our data identify AMPK as a molecular rheostat that actively represses steroid hormone biosynthesis to preserve cellular energy homeostasis and prevent excess steroid production.
Related Concept Videos
Amplifying Signals via Enzymatic Cascade
cAMP-dependent Protein Kinase Pathways
Intracellular Signaling Cascades
GPCRs Regulate Adenylyl Cylase Activity
MAPK Signaling Cascades
Regulation of Nuclear Protein Sorting

