Hypoxia-Inducible Factor 1 (HIF-1) regulates Sertoli cell lactate production

GALARDO MARÍA NOEL LUJÁN; REGUEIRA, MARIANA; RIERA MARÍA FERNANDA; PELLIZZARI ELIANA HERMINIA; CIGORRAGA SELVA BEATRIZ; MERONI SILVINA BEATRIZ

Chicago

Congreso; 16th International Congress of Endocrinology & The Endocrine Society?s 96th Annual Meeting & Expo (ICE/ENDO); 2014

ENDOCRINE SOCIETY

Sertoli cells (SC) provide the structural and nutritional support for germ cell development. Studies on SC glucose metabolism have shown that this cell type actively metabolizes glucose and converts it to lactate, which is the major source of energy for germ cells. On the other hand, the transcription factor HIF-1 plays a central role in the regulation of glycolytic metabolism. Active HIF-1 is a heterodimer consisting of an oxygen-dependent  subunit and a constitutively expressed  subunit. Under normoxic conditions,  subunit is rapidly degraded via a mechanism that involves hydroxylation by oxygen-dependent prolyl-hydroxylases. Prolyl-hydroxylases inhibition ?by low oxygen tension or transition metals like cobalt? leads to HIF-1 subunit stabilization, which enables HIF-1  and  subunits to associate and form active HIF-1. The aim of this work was to evaluate HIF-1 participation in the regulation of molecular mechanisms involved in lactate production in SC. In order to augment HIF-1 levels, 20-day-old rat SC cultures were incubated for different periods of time in the presence of cobalt chloride (CoCl2 300μM). HIF-1 protein levels, lactate production and different mechanisms involved in its production such as: glucose uptake, LDH activity and the expression of GLUT1, MCT4, LDHA and PDK1 were analyzed. As expected, Western blot analysis showed that CoCl2 increased HIF-1 (CoCl2: 5.4±0.5*, *p