Adiponectin is a protein hormone mainly produced by adipocytes. It plays an essential role in the regulation of lipid and carbohydrate metabolisms. Adiponectin mediates its effects through mainly two receptors named AdipoR1 and AdipoR2. Some evidence in rodent and domestic animals suggests that adiponectin could also regulate female fertility and more particularly ovarian functions. However, its role in human ovary has never been investigated. The objectives of the present study were to identify adiponectin and adiponectin receptors 1 and 2 in human ovary and to determine the effects of human recombinant adiponectin on in vitro human granulosa cells (GC) steroidogenesis. We have also investigated which signaling pathways could be activated by adiponectin in human GC. We showed using Reverse Transcription-Polymerase Chain Reaction and Western blot that the mRNAs for AdipoR1 and AdipoR2 and the proteins are found in human GCs. In these latter cells, expression of adiponectin (mRNA and protein) was undetectable, whereas it was largely expressed in human theca cells. By ELISA assay, we detected higher levels of adiponectin in fluid follicular than in plasma. In the second part of our study, we observed that human recombinant adiponectin increased IGF-1-induced progesterone and estradiol (E2) production in human GCs without any variation of StAR, p450scc and 3βHSD protein levels. However, we showed that adiponectin treatment increased IGF-1-induced E2 secretion and this was associated with an increase in the protein amount of p450 aromatase. Finally, we observed that adiponectin treatment rapidly increased the MAPK (ERK1/2 and p38) signaling pathway in human GCs. These findings significantly increase our understanding of the role of adiponectin on human GCs. However, further investigations are required to determine the role of adiponectin on other human ovarian cells including theca cells and also its potential implication in the polycystic ovary syndrome.
25 - 29 Apr 2009
European Society of Endocrinology