Evidence for a negative feedback role of inhibin in follicle stimulating hormone regulation in women

Abstract

The pituitary--ovarian axis describes a regulatory system in which pituitary gonadotrophins stimulate ovarian folliculogenesis and the production of both steroid and protein hormones, which in turn exercise feedback control on the pituitary and hypothalamus. The availability of a radioimmunoassay for serum inhibin has allowed exploration of inhibin's role in the regulation of follicle stimulating hormone (FSH). This gonadotrophin stimulates ovarian inhibin secretion within the physiological dose range, both after exogenous administration and during endogenous rises, as are seen during puberty and the mid-cycle FSH surge. No direct evidence of FSH suppression by inhibin administered to human subjects has been obtained. During periods of endogenously raised inhibin levels, however, FSH is suppressed, as seen during the luteal phase of the menstrual cycle (luteinizing hormone drives inhibin production at that time), during pregnancy and in patients with inhibin-secreting granulosa cell tumors of the ovary. In contrast, decreased inhibin levels in the presence of intact hypothalamo-pituitary function result in increased FSH concentrations--as in early childhood, during the luteal-follicular transition and during reproductive ageing. After the menopause inhibin levels are normally undetectable, with FSH being markedly elevated. These observations are compatible with a role for endogenous inhibin in the regulation of FSH, though the contribution of oestradiol is in most instances impossible to dissect out separately.