METFORMIN COUNTERACTS THE EFFECTS OF FSH ON RAT SERTOLI CELL PROLIFERATION

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

REPRODUCTION

BIOSCIENTIFICA LTD

Año: 2018 vol. 156 p. 93 - 101

1470-1626

Metformin is one of the most widely used anti-hyperglycemic agents for treatingpatients 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 Metformin, 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 8-day-old rat Sertoli cell cultures. The results obtained show that Metformin in the presence of FSH increases phosphorylated ACC and decreases phosphorylated p70S6K levels. Moreover, we show that Metformin 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 Metformin can, at least in part, counteract the effect of FSH on postnatal Sertoli cell proliferation.