부산대학교 도서관

Objective: Obesity is a cause and a consequence of hormonal dysregulation in men. To reach a successful spermatogenesis a strict hormonal regulation is necessary, being the Sertoli cells (SCs) the majors hormonal targets in the testis. The main goal of this work is to study the effects of hormones known to be dysregulated in obesity (leptin, ghrelin and glucagon-like peptide-1 (GLP-1)) in human SCs (hSCs) metabolism. Methods: Human SCs were exposed to leptin (5, 25 and 50 ng/mL), ghrelin (20, 100 and 500 pM) and GLP-1 (0.01, 1 and 100 nM). These concentrations were chosen to mimic the hormonal levels of men with different body mass index. PCR was used to evaluate the mRNA presence of hormone receptors. Intermediary metabolites were assessed by NMR and expression of proteins involved in the metabolism of SCs was determined by Western blot. Slot blot was used to evaluate carbonylation, lipid peroxidation and nitration. Mitochondrial and lactate dehydrogenase (LDH) activity were analyzed using commercial kits. Results: We identified the receptors of leptin, ghrelin and GLP-1 in hSCs. Cells exposed to leptin increased glucose transporter 2 (GLUT2) protein levels and LDH activity while acetate production decreased. A pro-oxidative profile was observed in hSCs exposed to low concentrations of ghrelin where pyruvate consumption was increased with no alteration in lactate production. The same oxidative profile and alteration in pyruvate consumption was found when hSCs were exposed to high concentrations of ghrelin, but lactate production decreased. The exposure of hSCs to GLP-1 increased lactate production. And the highest concentration of GLP-1 was responsible for a decrease in markers of oxidative stress. Conclusion: Leptin, ghrelin and GLP-1 modulate the metabolism of hSCs which has implications in the nutritional support of spermatogenesis and thus in the fertility potential of males. º Both authors contributed equally.