TGF-β1 System in Leydig Cells. Part I: Effect of hCG and Progesterone

Transforming growth factor beta 1 (TGF-beta 1) modulates male reproductive function. Genetically modified mice overexpressing alpha/beta subunits of hCG (hCG+) show Leydig cell hyperplasia / hypertrophy at prepuberty that disappears as the mice approach adulthood. In this study we analyzed the gene expression of TGF-beta 1, its specific receptors, type II (TGF-beta RII) and type I (activin receptor-like kinase 1 and 5: ALK1 and ALK5), and co-receptor endoglin (CD105) in purified Leydig cells from hCG+ and wild-type mice at 3 and 8 weeks of age and the occurrence of TGF-beta 1, ALK1 and ALK5 by immunohistochemistry. The expression of TGF-beta 1 was higher in hCG+ mice at both ages studied, and no changes were observed in TGF-beta RII. ALK5 diminished with age in wild-type mice, whereas ALK1 decreased in hCG+ mice at 8 weeks of age. Endoglin expression showed a marked increase in 3-week-old hCG+ animals. In vitro incubation of Leydig cells from wild-type animals with hCG (10 IU/ml) increased TGF-beta 1 and ALK5 expression. Progesterone (10(-6) M) induced endoglin expression. These studies provide novel evidence for differential gene and protein expression of ALK1 and ALK5 at different ages and endoglin expression and hormonal, in purified Leydig cells.