Adiponectin, Resistin, and Glucose Transporters During the Periovulatory Interval in Rhesus Macaques.

Abstract

Adiponectin and resistin are part of the adipokine family of hormones produced and secreted by adipose tissue. Circulating adiponectin is associated with increased adiposity and can promote glucose uptake, possibly via increased expression and/or activation of glucose transporters. In addition, a role for adiponectin in reproductive function has been put forth to include effects on ovulation and steroidogenesis. Resistin, in contrast, may be more closely linked to inflammation, although there is some evidence that resistin is associated with insulin resistance. The goal of this study was to examine intra-follicular and serum concentrations of adiponectin and resistin during the periovulatory interval in rhesus monkeys undergoing controlled ovarian stimulation (COS), as well as determine the expression of adiponectin receptors during granulosa cell luteinization. Adult females were treated with recombinant human follicle-stimulating hormone for 7 days and follicles were aspirated before (0 hr), 3, 6, 12, and 24 hr after ovulatory bolus of hCG. Follicular fluid and serum levels of adiponectin and resistin were measured by ELISA before (0 hr) and 24 hr after hCG. Adiponectin decreased (p<0.05) 24 hr after hCG treatment while serum levels remained unchanged. In contrast, follicular fluid levels of resistin were unchanged after hCG, while serum concentrations increased 24 hr post-hCG. The mRNA expression of adiponectin and adiponectin receptors (AdipoR) I and II were analyzed using RT-PCR. Adiponectin mRNA was not detectable in granulosa cells at any time point. However, AdipoRI expression was increased transiently 3 hrs after hCG (5.5-fold, p<0.05), while AdipoRII mRNA was elevated 3 and 6 hrs after hCG treatment before returning to 0 hr levels (6- and 23-fold, respectively; p<0.05). Granulosa cells isolated prior to hCG in vivo were cultured with FSH or FSH+hCG +/- adiponectin (0-25 µg/ml). In the presence of FSH only, adiponectin increased progesterone levels (0 µg/ml adiponectin: 1.7 ng/ml ±0.2; 5 µg/ml: 2.0 ± 0.3; 25 µg/ml: 8.9 ± 0.7). Similarly, hCG markedly increase progesterone over FSH alone (7.7-fold; p<0.05), although adiponectin did not further increase progesterone. Adiponectin did not alter the mRNA expression of glucose transporters (GLUT) 1, 2, or 4, but in the presence of hCG, dose-dependently increased GLUT3 mRNA (p<0.05). These data confirm and quantify the presence of adiponectin and resistin in the luteinizing primate follicle, as well as the dynamic expression of adiponectin receptors. Importantly, the lack of granulosa cell expression of adiponectin mRNA indicates a complex origin for follicular adiponectin. A limited local role for adiponectin through its increased receptors may facilitate glucose uptake by luteinizing granulosa cells. Supported in part by NIH HD043358 (CLC) RR00169 (CNPRC) and RR13439 (CAV). (poster)