Merck
  • Home
  • Search Results
  • A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis.

A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis.

Molecular and cellular biology (2014-09-17)
Houssein S Abdou, Francis Bergeron, Jacques J Tremblay
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
フォルスコリン, from Coleus forskohlii, ≥98% (HPLC), powder
Sigma-Aldrich
フォルスコリン, For use in molecular biology applications
Sigma-Aldrich
プロゲステロン, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
AICAR, ≥98% (HPLC), powder
Sigma-Aldrich
テストステロン, ≥98%
Sigma-Aldrich
(−)-アデノシン3′5′-サイクリック一リン酸, ≥98.5% (HPLC), powder
Sigma-Aldrich
(−)-アデノシン3′5′-サイクリック一リン酸 ナトリウム塩 一水和物, ≥98.0% (HPLC), powder
Supelco
テストステロン 溶液, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
テストステロン, purum, ≥99.0% (HPLC)
Supelco
プロゲステロン, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
プロゲステロン 溶液, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
フォルスコリン, analytical standard
Sigma-Aldrich
プロゲステロン, meets USP testing specifications
Sigma-Aldrich
プロゲステロン, γ-irradiated, BioXtra, suitable for cell culture
Supelco
テストステロン, VETRANAL®, analytical standard
USP
プロゲステロン, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
22(R)-ヒドロキシコレステロール, ≥98%
Sigma-Aldrich
アデノシン 3′,5′-環状一リン酸 トリス塩, ≥97% (HPLC), powder
Sigma-Aldrich
Adenosine 2′(3′)-monophosphate mixed isomers
プロゲステロン, European Pharmacopoeia (EP) Reference Standard
テストステロン, European Pharmacopoeia (EP) Reference Standard
Supelco
プロゲステロン, VETRANAL®, analytical standard