info:eu-repo/semantics/article
HIF involvement in the regulation of rat Sertoli cell proliferation by FSH
Fecha
2018-08Registro en:
Gorga, Agostina; Rindone, Gustavo Marcelo; Regueira, Mariana; Riera, Maria Fernanda; Pellizzari, Eliana Herminia; et al.; HIF involvement in the regulation of rat Sertoli cell proliferation by FSH; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 502; 4; 8-2018; 508-514
0006-291X
CONICET Digital
CONICET
Autor
Gorga, Agostina
Rindone, Gustavo Marcelo
Regueira, Mariana
Riera, Maria Fernanda
Pellizzari, Eliana Herminia
Cigorraga, Selva Beatriz
Meroni, Silvina Beatriz
Galardo, Maria Noel Lujan
Resumen
The final number of Sertoli cells reached during the proliferative periods determines sperm production capacity in adulthood. It is well known that FSH increases the rate of proliferation of Sertoli cells; however, little is known about the transcription factors that are activated by the hormone in order to regulate Sertoli cell proliferation. On the other hand, Hypoxia Inducible Factors (HIFs) are master regulators of cell growth. HIFs are dimers of HIF-β and HIF-α subunits. Considering that HIF-β is constitutively expressed, HIF transcriptional activity is regulated through the abundance of HIF-α subunits. To date, three HIF-α isoforms have been described. The association of the different HIF-α subunits with HIF-β subunit constitutes three active transcription factors —HIF-1, HIF-2 and HIF-3— which interact with consensus hypoxia-response elements in the promoter region of target genes. Hypoxia has been classically considered the main stimulus that increases HIF transcriptional activity, however, regulation by hormones under normoxic conditions was also demonstrated. The aim of this work has been to investigate whether HIFs participate in the regulation of rat Sertoli cell proliferation by FSH. Sertoli cells obtained from 8-day old rats were cultured in the absence or presence of FSH. It has been observed that FSH increases HIF transcriptional activity and HIF-2α mRNA levels without modifying either HIF-1α or HIF-3α expression. Incubations with FSH have been also performed in the absence or presence of a pharmacological agent that promotes HIF-α subunit degradation, LW6. It has been observed that LW6 inhibits the FSH effect on proliferation, CCND1 expression and c-Myc transcriptional activity. Altogether, these results suggest that HIFs might be involved in the regulation of Sertoli cell proliferation by FSH.