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Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner

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Abstract

Obesity in men is associated with lower testosterone levels, related to reduced sperm concentration and the development of various diseases with aging. Hormones produced by the adipose tissue may have influences on both metabolism and reproductive function. Among them, the production and secretion of adiponectin is inversely correlated to total body fat. Adiponectin receptors (AdipoR1 and AdipoR2) have been found to be expressed in testicular Leydig cells (producing testosterone). Since StAR and Cyp11a1 are essential for testosterone synthesis and adiponectin has been shown to regulate StAR mRNA in swine granulosa cells, we hypothesized that adiponectin might also regulate these genes in Leydig cells. Our objective was to determine whether adiponectin regulates StAR and Cyp11a1 genes in Leydig cells and to better define its mechanisms of action. Methods used in the current study are qPCR for the mRNA levels, transfections for promoter activities, and enzyme-linked immunosorbent assay for the progesterone concentration. We have found that adiponectin cooperates with cAMP-dependent stimulation to activate StAR and Cyp11a1 mRNA expressions in a dose-dependent manner in MA-10 Leydig cells as demonstrated by transfection of a luciferase reporter plasmid. These results led to a significant increase in progesterone production from MA-10 cells. Thus, our data suggest that high doses of adiponectin typical of normal body weight may promote testosterone production from Leydig cells.

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Acknowledgments

Current work was funded by the New Brunswick Innovation Foundation (NBIF) (#IAR2012 and IAR2013-029 to L.J.M.), the New Brunswick Health Research Foundation (NBHRF) (#2010-SEED-178 and 2013-OG to L.J.M.), and the Natural Sciences and Engineering Research Council (NSERC) of Canada (#386557-2012 to L.J.M.). We would like to thank Dr. Mario Ascoli (University of Iowa, Iowa City, Iowa) for generously providing the MA-10 cell line. We are also grateful to Dr. Jacques J. Tremblay (Université Laval, Québec, Qc), Dr. Michael Wegner (Institut für Biochemie, Universität Erlangen, Germany), and Dr. James Wells (Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH) for kindly providing plasmid constructs used in this study.

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Landry, D., Paré, A., Jean, S. et al. Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner. Endocrine 48, 957–967 (2015). https://doi.org/10.1007/s12020-014-0456-y

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