MODULATION OF TGF-beta1 AND VEGFA EXPRESSION IN TESTES OF TRANSGENIC MICE OVER-EXPRESSING hCG. IN VITRO EFFECT OF hCG, PROGESTERONE AND TESTOSTERONE IN FVB/N MICE TESTES

CANDELA R. GONZALEZ; BETINA GONZALEZ; SUSANA RULLI; ILPO HUHTANIEMI; RICARDO CALANDRA; SILVIA GONZALEZ-CALVAR

Toronto, Canada

Congreso; The Endocrine Society´s 89th Annual Meeting; 2007

The Endocrine Society

MODULATION OF TGF-b1 AND VEGFA EXPRESSION IN TESTES OF TRANSGENIC MICE OVER-EXPRESSING hCG. IN VITRO EFFECT OF hCG, PROGESTERONE AND TESTOSTERONE IN FVB/N MICE TESTES. Gonzalez C1, Gonzalez B1, Rulli S1, Huhtaniemi I2, Calandra R1,3, Gonzalez Calvar SI1,4 1IBYME, CONICET, Argentina, 2 University of Turku, Finland, 3IMBICE, Argentina, 4 School of Medicine, UBA, Argentina. E-mail: cgonzalez@dna.uba.ar Transgenic male mice (TG) over-expressing a and b subunits of hCG are infertile and show enhanced steroidogenesis with high levels of testosterone (T) and progesterone (P4). The chronic hCG hyper-stimulation leads to Leydig cell hyperplasia and hypertrophy in prepubertal mice, being reduced at adulthood (Rulli et al; Endocrinology, 144: 4980, 2003). Transforming growth factor-b1 (TGF-b1) belongs to a superfamily of growth factors and acts via TGF-b type II and type I receptors to inhibit proliferation. However, in the presence of endoglin, a TGF-b1 co-receptor, this process is stimulated. Several reports indicate that TGF-b1 is involved in vascular endothelial growth factor (VEGFA) expression. The aim of this study was to analyze the expression of TGF-b1, endoglin and VEGFA in the testes of TG at 3 and 8 weeks of age (w). We also analyzed the “in vitro” effect (1 h) of hCG (10 UI/ml), P4 (10-5 M) and T (10-6 M) on TGF-b1, VEGFA and endoglin testicular expression in wild type mice (FVB/n) at both ages, as well as the effect of TGF-b1 on VEGFA and endoglin expression at 8w. VEGF TGF-b TG showed an increase in the expression of: 1) TGF-b1 at 8w (p<0,05); 2) VEGF-A at both ages (p<0,05) and 3) endoglin at 3w (p<0,05). “In vitro” incubation with hCG induced the expression of TGF-b1 at both ages studied (p<0.05). Incubation with P4 had no effect on TGF-b1 expression, but produced a significant increment on endoglin expression levels at 3w (p<0.05). Experiments with T only produced a significant increment on VEGFA expression at 3w (p<0.05). “In vitro” incubation (15 or 30 min.) with 1 ng/ml of TGF-b1 induced an increase in testicular VEGFA expression, whereas a decrease on this parameter was observed at 10 ng/ml of TGF-b1 (p<0,05). Immunohistochemistry showed that VEGFA is localized in Leydig and Sertoli cells. In summary, high and chronic levels of hCG induced testicular TGF-b1 expression on TG at 8w. “In vitro” experiments show that TGF-b1 might be regulated by hCG, and that P4 and T would modulate endoglin and VEGFA expression respectively. The expression of endoglin in TG, suggests its involment in testicular cell proliferation in prepubertal animals. Furthermore, “in vitro” studies showed that TGF-b1 exerted a biphasic effect on VEGFA levels. The temporal expression of these factors might play a role in the growth and development of the testes. These results prompt us to speculate that abnormal levels of these factors might disturb testicular function.