title: Differential effects of leptin on ovarian metalloproteinases and their tissue inhibitors between in vivo and in vitro studies.
abstract: In this study, we investigated the effect of leptin on the ovarian metalloproteinase system in the rat during the ovulatory process. Ovulation was induced in immature rats primed with gonadotropins. In both in vitro and in vivo experiments, we measured i) the protein expression of the ovarian metalloproteinases (matrix metalloproteinases, MMPs) and their tissue inhibitors (TIMPs) by western blot; ii) the gelatinase activity of the ovarian MMPs by zymography; and iii) the inhibitory action of TIMPs by reverse zymography. Using cultures of ovarian explants, leptin increased the activity but not the protein expression of MMP-2 and MMP-9 in both culture medium and ovarian tissue, and the protein expression of TIMPs, without a higher inhibitory action of the gelatinase activity. These results suggest either that the increase in TIMP proteins was not sufficient or that the inhibitory actions of TIMPs were impaired to suppress the MMP activity when the ovaries were directly exposed to leptin. To study the in vivo effect, rats received an acute treatment with high doses of leptin to inhibit ovulation. This treatment increased the expression of both the latent and the active forms of MMP-2 but did not result in a greater activity of MMP-2. In addition, the inhibitory action of TIMP-2 was also increased by this treatment. These results suggest that the administration of high doses of leptin could be regulating the follicle wall degradation, at least in part, by increasing the action of the ovarian TIMP-2 as a result of an extraovarian mechanism or signaling pathway.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, UBA, Paraguay 2155, 16° P, C1121ABG Buenos Aires, Argentina.
authors.forename: M G
authors.initials: MG
authors.lastname: Bilbao
authors.forename: M P
authors.initials: MP
authors.lastname: Di Yorio
authors.forename: A G
authors.initials: AG
authors.lastname: Faletti
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005260:Female; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D020738:Leptin; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases