TGF-β1 System in Leydig Cells. Part II: TGF-β1 and Progesterone, Through Smad1/5, are Involved in the Hyperplasia/hypertrophy of Leydig Cells

Several reports indicate that transforming growth factor β1 (TGF-β1) participates in the regulation of cell cycle progression. In this work, we analyzed the in vitro effect of TGF-β1 on Leydig cell proliferation markers and the in vivo effect of this cytokine in Leydig cell hyperplasia/hypertrophy. The in vitro effect of TGF-β1 (1 ng/ml) plus progesterone (10-6 M) on purified Leydig cells from 3 week-old mice increased the immunocytochemically detected PCNA and stimulated the phosphorylation of Smad 1/5. Progesterone (10-6 M) in the presence or absence of TGF-β1 diminished the ratio Bax/Bcl-2. Morphometric testicular studies of mice treated with progesterone (s.c.) plus TGF-β1 (intratesticular), showed an increase in interstitial volume and a decrease in tubular volume. Furthermore, the cytoplasmic volume of Leydig cells showed an increment in this experimental group with a diminution in nuclear volume. Thus, it turned out that the administration of progesterone and TGF-β1 augmented the volume of Leydig cells. These results indicate a clear effect of TGF-β1 in the hypertrophy/hyperplasia of Leydig cells.