Extracellular signal-regulated kinases (ERK) 1, 2 are required for luteinizing hormone (LH)-induced steroidogenesis in primary Leydig cells and control steroidogenic acute regulatory (StAR) expression.
The luteinizing hormone (LH) plays a critical role in steroidogenesis, by stimulating cAMP-dependent protein kinase A (PKA) and phospholipase A2 activity, and by mobilizing calcium and chloride ions. In contrast, whether the ERK 1, 2 mitogen-activated protein (MAP) kinases are involved in LH-induced steroidogenesis is less obvious. Here, we sought to clarify this point in rat primary Leydig cells, naturally bearing the LH receptor (LH-R) in male, and in the mouse tumoral Leydig cell line (MLTC 1). Pre-incubation of both cell types with the mitogen-activated protein kinase kinase (MEK) inhibitors U0126 and PD98059 reduced LH-induced steroidogenesis, and tonically enhanced the expression of the StAR protein. Furthermore, ERK1, 2 were inducibly phosphorylated following LH exposure of MLTC 1 cells. Altogether, our results indicate that in primary as well as in tumoral Leydig cells, inhibiting MEK dampened LH-induced steroidogenesis but enhanced basal as well as LH-induced StAR expression, suggesting that ERK1,2 could be involved in these responses.
Martinat
Nadine
N
Institut National de la Recherche Agronomique/Centre National pour la Recherche Scientifique/Université de Tours/Haras Nationaux, UMR 6175, Centre de Recherches de Tours, 37380 Nouzilly, France. martinat@tours.inra.fr
Crépieux
Pascale
P
Reiter
Eric
E
Guillou
Florian
F
D000818:Animals; D045744:Cell Line, Tumor; D015151:Immunoblotting / Q000662:veterinary; D007985:Leydig Cells / Q000201:enzymology / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D011374:Progesterone; D007986:Luteinizing Hormone; D048052:Mitogen-Activated Protein Kinase 3