Heat shock-induced inhibition of acute steroidogenesis in MA-10 cells is associated with inhibition of the synthesis of the steroidogenic acute regulatory protein.
The synthesis of heat shock proteins (HSPs) rapidly increases in cells under a broad range of stress conditions in addition to heat shock. Previous studies have shown that the induction of HSPs severely impairs the ability of steroidogenic cells to synthesize steroids in response to acute stimulation. De novo synthesis of the steroidogenic acute regulatory (StAR) protein has been shown to be indispensable for acute steroid hormone biosynthesis; however, the effect of HSP induction on the synthesis of the StAR protein has not yet been studied. In the present study we investigated whether HSP induction might influence the steroidogenic activity of MA-10 mouse Leydig tumor cells, and whether this effect may involve the synthesis of StAR protein. MA-10 cells exposed to 45 C for 10 min and allowed to recover for 2 h at 37 C displayed a 6-fold increase in HSP-70 at 3 h postrecovery and a 20-fold increase in this protein at 6 h postrecovery. This heat shock regimen also acutely inhibited both progesterone production and StAR protein synthesis in MA-10 cells in response to LH and cAMP analog stimulation. The activity and quantity of cytochrome P450 side-chain cleavage and 3beta-hydroxysteroid dehydrogenase were not affected by this heat shock treatment, indicating that the loss of steroidogenic capacity was not a result of inhibition of the enzymes involved in the conversion of cholesterol to progesterone. The results suggest that the previously observed antisteroidogenic effects of heat shock treatment may be due mainly to the acute inhibition of StAR protein synthesis.
Liu
Z
Z
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Stocco
D M
DM
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011374:Progesterone / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D000098682:Steroidogenic Acute Regulatory Protein
D018840:HSP70 Heat-Shock Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme