Assessment of the role of Hypoxia Inducible Factors (HIFs) in FSH regulation of Sertoli cell proliferation

GALARDO MN; RINDONE GM; GORGA A; CIGORRAGA SB; PELLIZZARI EH; RIERA MF; REGUEIRA M; CAMBEROS MC; MERONI SB

Mar del Plata

Congreso; LXI Reunión Científica de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investígación Clínica

The final number of Sertoli cells (SC) reached during the proliferative periods determines sperm production capacity in adulthood. It is well known that FSH is the major SC mitogen; however, little is known about the transcription factors involved in the regulation of SC proliferation. On the other hand, Hypoxia Inducible Factors (HIFs) are master regulators of cell growth. HIFs consist of a constitutive HIFbeta (HIFb) subunit and a HIFalpha (HIFa) subunit. HIF transcriptional activity is regulated through the abundance of HIFa subunits. To date, three HIFa isoforms have been described. The association of each HIFa subunit with HIFb subunit constitutes three active transcription factors: HIF1, HIF2 and HIF3, which interact with consensus hypoxia response element in the promoter region of target genes. Besides, regulation by hormones of HIF transcriptional activity under normoxic conditions was demonstrated. The aim of this work was to investigate whether HIFs participate in the regulation of rat SC proliferation by FSH. SC obtained from 8-day old rats were maintained under basal (B) conditions or stimulated with FSH 100 ng/ml in the absence or presence of a pharmacological agent that promotes HIFa subunit degradation LW6. BrdU incorporation, HIF transcriptional activity by gene reporter assay and HIF1a, HIF2a, HIF3a and cyclin D1 (CCND1) expression by RT-qPCR were evaluated. Results are expressed as mean±SD of three independent experiments (*P