Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance

Abstract

We studied the in vitro response to insulin of granulosalutein cells derived from patients with polycystic ovary syndrome (PCOS) and clinically defined insulin resistance. Insulin sensitivity was assessed by continuous infusion of glucose with model assessment test (CIGMA). Insulin resistant (PCOS-IR; n = 8), non-insulin resistant (PCOS-NIR; n = 9) patients with PCOS, and women with tubal factor infertility (TF; n = 8) underwent controlled ovarian stimulation with long-term gonadotropin-releasing hormone (GnRH) agonist, recombinant follicle stimulating hormone (FSH), and in vitro fertilization. Primary cultures of granulosa-lutein cells were incubated with insulin (10, 100, 500 ng/ml) and/or luteinzing hormone (LH) (10, 100 ng/ml) in the presence of low density lipoprotein (100 μg/ml). The progesterone and lactate accumulation were measured in the culture medium. LH potently stimulated the progesterone secretion in all groups. Insulin alone had no effect on progesterone release in any of the groups, but stimulated lactate formation in the PCOS-NIR and TF groups. Insulin augmented the effect of LH on progesterone secretion selectively in the PCOS-NIR group. The expression of the insulin receptor was determined by Western blotting in separate cultures of granulosa-lutein cells, and showed receptor down-regulation in the PCOS-IR patients. We infer that the in vitro effect of insulin on progesterone and lactate release by granulosa-lutein cells is impaired in insulin resistant PCOS patients.