| Leptin, a hormone produced by adipocytes, controls body weight and energy expenditure. Its role in reproduction includes important actions on the hypothalamus to induce release of gonadotropin releasing hormone, (GnRH), thereby triggering gonadotropin release and leading to development of the reproductive tract and induction of puberty. A direct involvement of leptin in ovarian function has been postulated. Indeed, the expression of leptin receptors has been shown in human, mouse, and rat ovaries.; The intracellular pathway triggered by leptin at the ovary level is not well known. In other tissues, the transcription factor, S&barbelow;ignal of T&barbelow;ransduction and A&barbelow;ctivation of T&barbelow;ranscription-3 (STAT-3) has been found as one of the first elements in the cascade. There are other plausible candidate genes such as the S&barbelow;terol R&barbelow;egulatory E&barbelow;lement B&barbelow;inding P&barbelow;rotein (SREBP-1) and the S&barbelow;teroid A&barbelow;cute R&barbelow;egulatory protein (StAR) since they are implicated in the regulation and metabolism of steroids. In addition, it is well known that SREBP-1 is a regulator of StAR expression, increasing the interest of studying these two proteins.; The purposes of our investigation were to determine the sequence and homologies with other species of the porcine leptin receptor, and its expression (the messenger RNA and protein levels) during in vivo and in vitro differentiation of ovarian cells.; Data indicate that leptin receptor mRNA and protein abundance vary during granulosa cells luteinization in vitro and in the corpus luteum (CL) during the pig luteal phase. We undertook the production and purification of recombinant porcine leptin and we demonstrated direct effects on porcine granulosa cells in vitro. Indeed, when cells are treated with two different doses of leptin there is a biphasic effect (low doses being stimulatory and high doses inhibitory) on progesterone accumulation, SREBP-1 protein abundance and in the activation of transcription of the StAR promoter in granulosa cells co-transfected with the active form of SREBP-1. Concerning the STAT-3 protein, both low and high doses seem to stimulate its expression.; We conclude that leptin receptor is expressed in granulosa and luteal cells, and varies during pig ovarian cell differentiation. After binding to its receptor, leptin, acting through STAT-3, modulates steroidogenesis in a biphasic and dose-dependent manner, and SREBP-1 induction of StAR expression may be in the cascade of regulatory events. |
