REGULATION OF SERTOLI CELL (SC) PROLIFERATION BY LACTATE.

CENTOLA CL; DASSO ME; RIERA MF; MERONI SB; GALARDO MN

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SAIC; 2023

Sociedad Argentina de Investigación Clínica

The final number of SCs, reached during the proliferative periods, defines the spermatogenic capacity in adulthood. It is recognized that FSH is the main mitogen targeting SCs and that it exerts its action, at least partly, through the activation of the PI3K/Akt/mTORC1 pathway. We have recently shown that FSH simultaneously upregulates proliferation and aerobic glycolysis in an mTORC1-dependent manner, and that aerobic glycolysis is required to achieve full mTORC1 activation. In the last decade, the study of metabolites as second messengers capable of modifying signalling pathways activity has gained interest. New evidence suggests that lactate, the end product of aerobic glycolysis, is responsible for the complete activation of mTORC1 in proliferating cells. Although the necessity of a high glycolytic flux in immature SC to maintain the proliferation rate has been evinced, the molecular mechanisms remain obscure. The aim of this study was to assess whether lactate (Lac) is able to regulate mTORC1 signalling pathway and consequently SC proliferation. SC obtained from 8-day old rats were maintained under basal conditions (B) or stimulated with 20 mM Lac in the absence or presence of 1nM rapamycin (Rap), an mTORC1 specific inhibitor. Phosphorylated (P)-mTORC1 and P-p70S6K levels by Western blot, and bromodeoxyuridine (BrdU) incorporation by immunocytochemistry were evaluated. It was observed that Lac increased P-mTORC1 and P-p70S6K levels, as well as BrdU incorporation. In addition, Rap was able to block Lac effect on SC proliferation (B: 8.5±0.7a, Rap: 7.3±0.5a, Lac: 11.7±1.3b, Lac+Rapa: 8.3±0.9% BrdU positive cells, mean±SD, n=3, different letters indicate statistically significant differences, P