Leptin effect on its receptors in the hypothalamus-pituitary-ovary axis

MARÍA PAULA DI YORIO; MARÍA GUILLERMINA BILBAO; ALICIA GRACIELA FALETTI

Buenos Aires

Congreso; XXII Latin-American and First Ibero-American Congress of Physiological Sciences; 2006

Sociedad Argentina de Fisiología

Leptin, the obese gene product, is synthesized and secreted by adypocytes and regulates appetite and energy expenditure through interaction with hypothalamic leptin receptors. Both the short and long isoforms of the leptin receptor are expressed not only in the hypothalamus but also in ovarian cells in both, human and rodents, suggesting that leptin may act directly on the ovary and modulate its function. In previous studies we demonstrated that high levels of leptin inhibited, while low levels induced the ovulatory process. The aim of this study was to investigate the effect of leptin on the expression of its receptors in the hypothalamic-pituitary-ovarian axis, by performing both studies using prepuberal rats stimulated with gonadotrophin and studies, using hypothalamic, pituitary and ovarian explant cultures. By western blotting assays, the expression of both leptin receptor isoforms (OB-Rl and OB-Rs) was found in hypothalamic and ovarian tissues. Densitometric analysis revealed that the administration of hCG induced an increase in OB-Rl protein expression, while the serum concentration of leptin diminished. In vitro studies showed that the expression of leptin receptors in ovarian tissue was augmented by the presence of high levels of leptin. Meanwhile their expression in hypothalamic tissue was biphasic, since it was reduced at low doses and increased at high doses of leptin, in comparison with controls. Unlike those tissues, in the anterior pituitary, OB-Rs protein displayed higher expression than OB-Rl, which was barely detected. Anyway, the expression of these receptors was increased by the presence of high doses of leptin, as occurred in ovarian tissue. These results suggest that leptin is able to modulate the expression of its own receptors in the hypothalamic-pituitary-ovarian axis in a differential way. Moreover, the positive or negative effect that leptin exert on the ovulatory process may be dependent of this regulation.