ACTIVATION OF OVARIAN SYMPATHETIC-NERVES IN POLYCYSTIC-OVARY-SYNDROME

Polycystic ovarian syndrome (PCOS) is one of the most common human ova rian pathologies affecting women of reproductive age. Despite extensiv e investigation, the etiology of PCOS remains poorly understood. Exper imentally, a PCO-like syndrome can be induced in rodents by a single d ose of the long-acting estrogen, estradiol valerate (EV). We have used this model to examine the possibility that PCOS is associated with de rangement of the sympathetic control of the ovary. The release of newl y incorporated norepinephrine (NE) from ovarian nerve terminals in res ponse to transmural stimulation of the gland increased significantly b efore the formation of cysts (30 days after EV injection) and remained elevated at the time when cysts form (60 days). The increase in evoke d NE release was accompanied by an augmented NE content and enhanced i ncorporation of [H-3]NE into ovarian tissue; both of these changes had been initiated by 30 days after EV treatment and became unambiguous a t the time of cyst formation. The overall increase in ovarian sympathe tic outflow suggested by these alterations in catecholamine homeostasi s was accompanied by a thecal cell-interstitial tissue selective down- regulation of beta-adrenergic receptors; the beta-adrenergic receptor concentration in these sympathetically innervated ovarian compartments was significantly lower in PCO than during the estrous phase of the e strous cycle, a time at which the beta-adrenergic receptor concentrati on reaches its lowest levels in normal cycling ovaries. Tyrosine hydro xylase activity was found to increase only when expressed per mg ovary , but not in absolute terms (i.e. per total ovary), suggesting regulat ion of enzyme activity by the enhanced catecholamine content. The resu lts demonstrate that an activation of the sympathetic neurons innervat ing the ovary precedes the development of cysts in EV-induced PCOS and raise the possibility that a derangement of sympathetic inputs to the ovary contributes to the etiology of PCOS.