Metformin counteracts the effects of FSH on rat Sertoli cell proliferation

RINDONE GUSTAVO; GORGA AGOSTINA; REGUEIRA MARIANA; PELLIZZARI ELIANA HERMINIA; CIGORRAGA SELVA BEATRIZ; GALARDO MARÍA NOEL; MERONI SILVINA BEATRIZ; RIERA MARÍA FERNANDA

REPRODUCTION

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2018 vol. 156 p. 1 - 9

1470-1626

Metformin (MET) is one of the most widely used anti-hyperglycemic agents for treating patients with type 2 diabetes and it has started to be used in pediatric population at ages when Sertoli cells are still proliferating. It is well known that follicle-stimulating hormone (FSH) is the major Sertoli cell mitogen. The aim of the study is to investigate a possible effect of MET, which has been shown to have anti-proliferative properties, on FSH regulation of postnatal Sertoli cell proliferation and on the molecular mechanisms involved in this regulation. The present study was performed in eight-day-old rat Sertoli cell cultures. The results obtained show that MET in the presence of FSH increases phosphorylated acetyl-CoA carboxylase and decreases phosphorylated p70S6K levels. Moreover, we show that MET decreases FSH-stimulated Sertoli cell proliferation, and this decrease is accompanied by a reduction in FSH-stimulated Cyclin D1 and Cyclin D2 expression and an increase in cell cycle inhibitor p21Cip expression. Altogether, these results suggest that MET can, at least in part, counteract the effect of FSH on postnatal Sertoli cell proliferation.