Stimulation of Ovarian Steroidogenesis and Ovulation in Mature Female Rats with Type 2 Diabetes Mellitus
摘要
Type 2 diabetes mellitus (T2DM) negatively impacts the femalereproductive system, however, hormonal and functional disturbancesin the ovaries and their response to luteinizing hormone receptor (LHR)agonists in T2DM have been poorly studied, and data on allostericLHR-agonists are lacking. The aim of the study was to evaluate theeffect of the allosteric LHR-agonist TP03 and human chorionic gonadotropin(hCG) on ovarian steroidogenesis and ovulation in female rats withdiet-induced T2DM. To induce ovulation, rats were administered Follimag(15 IU/rat) and Cetrotide (100 µg/rat, twice) in diestrus and TP03(25 mg/kg) or hCG (25 IU/rat) 48 h later, analyzing the parameters8 or 24 h after the injection of LHR-agonists. In T2DM rats, estradiollevels in the blood, the number of preovulatory follicles, and theexpression of the ADAMTS-1 metalloproteinase gene, an ovulationmarker, were decreased. Treatment with TP03 and hCG increased progesteronelevels (after 8 hours) and the expression of the ovarian genes Cyp17a1 (hCG, TP03) and Star (hCG), responsible for ovariansteroidogenesis, as well as the Adamts-1 gene.After 24 hours, corpora lutea were detected in the ovaries of T2DMrats, with hCG and TP03 being comparable in this parameter. Comparedto controls, T2DM rats maintained reduced estradiol levels, andthe stimulating effect of LHR-agonists on ovarian gene expression wasless pronounced. Thus, in T2DM, TP03 is not inferior to hCG in itsability to stimulate ovarian steroidogenesis and ovulation, andthis indicates the prospects for its use in assisted reproductivetechnologies for T2DM.