The NK3 receptor antagonist ESN364 interrupts pulsatile LH secretion and moderates levels of ovarian hormones throughout the menstrual cycle

Abstract

Women'shealth disorders such as uterine fibroids and endometriosis are currently treated byGnRH modulators that effectively suppress the hypothalamic-pituitary-gonadal axis. The neurokinin-3 receptor (NK3R) is an alternative target with an important role in the modulation of this axis. In this report,wedemonstrate that systemic administration of anNK3Rantagonist (ESN364) prolongs the LH interpulse interval in ovarectomized ewes and significantly lowers plasma LH and FSH concentrations in castrated nonhuman primates (Macaca fascicularis). Moreover, daily oral dosing of ESN364 throughout the menstrual cycle in M fascicularis lowered plasma estradiol levels in a dose-dependent manner, although ..