Regulation of Insulin Receptors in the Human Ovary:In VitroStudies*

Abstract

The association between insulin resistance and ovarian hyperstimulation has led to a hypothesis that insulin stimulates ovarian steroidogenesis. This possible effect of insulin on the ovary could be mediated by either the insulin receptor or the type I insulin-like growth factor (IGF) receptor, both of which have been described in the human ovary. We examined the in vitro regulation of insulin receptors by LH, FSH, multiplication-stimulating activity (MSA), and insulin in ovarian stromal fragments from 24 women. [125I]Insulin binding was measured in the presence and absence of increasing concentrations of insulin, IGF-I, LH, and FSH. Neither LH nor FSH competed with [125I]insulin for binding sites, but preincubation with LH or FSH reduced [125I]insulin binding by 19-38%. Preincubation with MSA reduced [125I]insulin binding by 34-48%. The affinity of the insulin receptors, determined by Scatchard analysis, did not change (Ka = 3.3 X 10(8) mol-1). A concentration of 10 ng/mL insulin in the preincubation medium reduced [125I]insulin binding by 40%, whereas an insulin concentration of 50 or 500 ng/mL completely obliterated specific [125I]insulin binding. [125I]Insulin binding fully recovered, however, 4 h after termination of tissue exposure to insulin. The specificity of [125I] insulin binding was confirmed by studies with IGF-I. We conclude that of the hormones examined, insulin is the most potent regulator of human ovarian insulin receptors in vitro. Down-regulation of insulin receptors by insulin was reversed within 4 h after withdrawal of insulin. MSA, FSH, and LH also down-regulated the number of human ovarian insulin receptors in vitro, but were less potent. These phenomena, if also present in vivo, could be important factors in the regulation of ovarian function by insulin in normal and pathological states.