Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells

Objective To identify adiponectin and its receptors (AdipoR1 and AdipoR2) in human granulosa cells (GC) and to study the effects of recombinant human adiponectin on P and E 2 secretion from these cells. Design The effects of recombinant human adiponectin on the secretion of P and E 2 by cultured human GCs were investigated. Setting Academic institutions. Patient(s) Seventeen infertile and healthy women undergoing IVF. Intervention(s) Primary human GC cultures stimulated with human recombinant adiponectin (5 μg/mL). Main Outcome Measure(s) Determination of messenger RNA (mRNA) and protein expression of adiponectin and its receptors AdipoR1 and AdipoR2 in fresh human GCs by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot, respectively. Measurement of P and E 2 levels in the conditioned media by RIA and determination of cell proliferation by tritied thymidine incorporation. Result(s) Human GCs express adiponectin receptors AdipoR1 and AdipoR2 but not adiponectin. In primary human GCs, adiponectin increases P and E 2 secretion in response to insulin-like growth factor I (IGF-I). This was associated with an increase in the p450 aromatase protein level but not those of p450scc, 3βHSD, or StAR. Adiponectin treatment does not affect IGF-1-induced cell proliferation and basal steroidogenesis (no IGF-1 or FSH stimulation). Adiponectin rapidly stimulates MAPK ERK1/2 and p38 phosphorylation in primary human GCs. Conclusion(s) Adiponectin receptors AdipoR1 and AdipoR2, but not adiponectin, are present in human GCs. Adiponectin increases IGF-1-induced P and E 2 secretion in primary human GCs.