The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic enzymes in Leydig cells

MATZKIN ME; YAMASHITA S; ASCOLI M

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2013 vol. 370 p. 130 - 137

0303-7207

Adult mice with a Leydig cell specific deletion of MAPK kinase (MEK) 1 and 2 (Mek1f/f;Mek2-/-;Cyp17iCre+) mice display hypergonadotropic hypogonadism.  We used radioimmunoassays and quantitative PCR to evaluate the function and expression of the Leydig cell genes involved in the conversion of cholesterol to testosterone (Star, Cyp11a1, Hsd3b6, Cyp17a1 and Hsd17b3), androgen metabolism (Srda1 and Dhrs9), and three nuclear receptors (Nr5a1, Nr4a1 and Nr0b1) that regulate expression of steroidogenic genes.  We show that Star, Hsd3b6, Cyp17a1 and Hsd17b3 are downregulated in adult Ledyig cells of Mek1f/f;Mek2-/-;Cyp17iCre+ mice whereas Srda1 and Dhrs9are upregulated and Nr5a1, Nr4a1 and Nr0b1 are unchanged or upregulated.  Functionally, all the downregulated genes but none of the upregualted genes contribute to the decrease in testosterone synthesis because decapsulated testes or Leydig cells from Mek1f/f;Mek2-/-;Cyp17iCre+ mice produce low testosterone when stimulated with hCG or when incubated with testosterone precursors such as progesterone or androstenedione.