INVESTIGADORES
ORTEGA Hugo Hector
artículos
Título:
Effect of prenatal steroid excess on intraovarian components of insulin signaling pathway and related proteins
Autor/es:
ORTEGA, HH; REY, F; VELAZQUEZ M; PADMANABHAN, V
Revista:
BIOLOGY OF REPRODUCTION
Editorial:
SOC STUDY REPRODUCTION
Referencias:
Año: 2010 vol. 82 p. 1065 - 1075
ISSN:
0006-3363
Resumen:
Prenatal testosterone (T) excess increases ovarian follicular recruitment, follicular persistence,
insulin resistance and compensatory hyperinsulinemia. Considering the importance of insulin in
ovarian physiology, in this study, using prenatal testosterone (T) and dihydrotestosterone (DHT,
a non-aromatizable androgen)-treated female sheep, we tested the hypothesis that prenatal
androgen excess alters intraovarian insulin signaling cascade and metabolic mediators that have
an impact on insulin signaling. Changes in ovarian insulin receptor (INSRB), insulin receptor
substrates 1 (IRS1), mammalian target of rapamycin (MTOR), phosphatidylinositol 3-kinase
(PIK3), peroxisome proliferator-activated receptor-gamma (PPARG) and adiponectin proteins
were determined at fetal (days 90 and 140), postpubertal (10 months), and adult (21 months)
ages by immunohistochemistry. Results indicated that these proteins are expressed in granulosa,
theca and stromal compartments with INSRB, IRS1, PPARG and adiponectin increasing in
parallel with advanced follicular differentiation. Importantly, prenatal T excess induced agespecific
changes in PPARG and adiponectin expression, with increased PPARG expression
evident during fetal life and decreased antral follicular adiponectin expression during adult life.
Comparison of developmental changes in prenatal T and DHT-treated females found that the
effects on PPARG were programmed by androgenic actions of T, while the effects on
adiponectin likely by its estrogenic action. These results suggest a role for PPARG in the
programming of ovarian disruptions by prenatal T excess including a decrease in antral follicular
adiponectin expression and a contributory role for adiponectin in follicular persistence and
ovulatory failure.