Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Abstract

To investigate the expression of leptin receptors (Ob-R) in the rat hypothalamus-pituitary-ovarian axis, immature rats were treated with eCG/hCG and Ob-R expression was evaluated by western blot analysis. The Ob-R expression increased 24 h after eCG administration in all the tissues assayed. In the hypothalamus, these levels immediately decreased to those obtained without treatment. In the pituitary, the Ob-R expression continued to be elevated 48 h after eCG administration, whereas the hCG injection did not modify these levels. Similar results were obtained with the ovarian long isoform. To assess the effect of leptin on its receptors, Ob-R was assessed in hypothalamus, pituitary and ovarian explants cultured in the presence or absence of leptin (0 . 3-500 ng/ml). In the hypothalamus, we found a biphasic effect: the Ob-R expression was either reduced or increased at low or high concentrations of leptin respectively. LH-releasing hormone secretion increased at 1 ng/ml. In the pituitary, Ob-R increased at 10 or 30 ng/ml of leptin for the long and short isoforms respectively. Leptin also induced an increase in LH release at 30 ng/ml. In the ovarian culture, the presence of leptin produced an increase in Ob-R expression at different ranges of concentrations and a dosedependent biphasic effect on the progesterone production. In conclusion, all these results clearly suggest that leptin is able to modulate the expression of its own receptors in the reproductive axis in a differential way. Moreover, the positive or negative effect that leptin exerts on the ovulatory process may be dependent on this regulation.

Ovarian signalling pathways regulated by leptin during the ovulatory process

“…The different responses obtained with these signalling proteins when the gonads are directly exposed to leptin might be related to different action mechanisms. The pattern of responsiveness obtained with p-STAT is i) similar to that observed by Ruiz-Corté s et al (2003) in porcine granulosa cell cultures, where both low (10 ng/ml) and high (1000 ng/ml) leptin levels increase STAT3 phosphorylation and ii) consistent with that found in the expression of OBRb in a previous study using rats treated with gonadotrophins to induce the first ovulation as in the present work (Di Yorio et al 2008). Thus, it is possible that, in the ovarian cells, the STAT3 phosphorylation caused by leptin is an OBRb-activated response.…”

“…Results are summarised in Table 2. The presence of leptin caused a dose-dependent biphasic effect on progesterone secretion, as described previously (Di Yorio et al 2008). Progesterone concentration was significantly increased at 1-10 ng/ml and decreased at 300 ng/ml.…”

“…The range of leptin concentrations was based on previous studies (Duggal et al 2000, Ricci et al 2006, and in the latter case, we used only those able to alter progesterone secretion, as described previously (Di Yorio et al 2008). After the incubation periods, ovarian tissues and the culture media were recovered and frozen on dry ice and stored at K72 8C until use.…”

“…These increases represented 83% for the 100 ng/ml concentration (P!0.01) and 39% for the 300 ng/ml concentration (P!0.05). Considering i) that the daily treatment with leptin induces (Roman et al 2005) and the acute treatment reduces (Ricci et al 2006) the levels of plasmatic progesterone, ii) that the presence of different levels of leptin causes a biphasic effect on progesterone secretion (Di Yorio et al 2008) and iii) to link the changes found in the signalling pathways to a downstream biological event, we measured the secretion of progesterone in the ovarian incubation medium. Results are summarised in Table 2.…”

In vitro effect of leptin on anterior pituitary cells LH secretory activity during early pregnancy in pig

“…Leptin acts on LH secretory activity via its specific receptor and is able to autoregulate its own receptors expression (Di Yorio et al 2008) and pituitary-derived leptin may act as an autocrine/paracrine factor within AP gland. Studies, primarily on ruminants and laboratory rodents, have established that leptin receptor is expressed in all types of AP cells, including gonadotropes (Iqbal et al 2000, Sone et al 2001.…”