Ovarian expression of alpha (1)- and beta (2)-adrenoceptors and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

Abstract

Polycystic ovary syndrome (PCOS) is the main cause of infertility in women. Despite extensive research aimed at identifying the pathogenetic mechanism underlying this condition, the aetiology of the disease is still unknown. Evidence from studies on women with PCOS and on an experimental rat polycystic ovary (PCO) model suggests that the sympathetic regulatory drive to the ovary may be unbalanced. The present study was designed to investigate this hypothesis. Accordingly, we used the well-defined rat PCO model, where PCO is induced by a single intramuscular (i.m.) injection of estradiol valerate (EV), and compared the model with oil-injected controls. We studied the ovarian expression of the α 1- and β 2-adrenoceptors (ARs), the neurotrophin receptor p75 (p75 NTR), and the sympathetic marker tyrosine hydroxylase (TH) at two time points: 30 and 60 days after EV injection. Our data demonstrate for the first time that all of the α 1-AR subtypes are expressed in normal rat ovaries at both the mRNA and the protein levels. Furthermore, the expression of the α 1-AR subtypes was differentially modulated in a time- and subtype-dependent manner in rats with EV-induced PCO. The ovaries in rats with steroid-induced PCO are characterised by an early overexpression of these molecules and p75 NTR, while the β 2-AR was downregulated. An increase in the expression of ovarian TH after EV injection was also detected, suggesting a structural and functional remodelling of ovarian sympathetic innervation in PCO rats. Our evidence strongly indicates that the role of the sympathetic nervous system is crucial in the pathogenesis of EV-induced PCO. Overall, our findings suggest that therapeutical approaches aimed at down-regulating the sympathetic tone to the ovary could be useful in the prevention and clinical treatment of PCOS.