Variations in plasma levels of substance P and effects of a specific substance P antagonist of the NK1 receptor on preovulatory LH and FSH surges andprogesterone secretion in the cycling cynomolgus monkey

These studies investigated the role of substance P (SP) in the regulation o f the hypothalamic-pituitary-ovarian axis in cynomolgus monkeys with normal menstrual cycles. Plasma concentrations of SP were determined in blood sam ples taken every morning in normally menstruating cynomolgus monkeys throug hout the menstrual cycle. There was a significant decreasing linear trend o f SP during the follicular phase (cycle day -13 to day 0) and a significant inverse relationship between SP plasma values and plasma 17 beta-estradiol (E-2) values from day -13 to day 0 of the adjusted cycle. Correspondingly, SP area under the curve was significantly greater during the follicular ph ase than the luteal phase. In a second experiment, plasma concentrations of E-2, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prog esterone and length of cycles were measured after five daily intragastric a dministrations (10 mg/kg) of an NK1 receptor (SP receptor) antagonist (RPR 100893; 10 mg/kg) initiated after serum E-2 concentrations had exceeded 125 pg/ml. There was a statistically significant reduction in the amplitude (4 1% of control) and the area under the curve (37% of control) of the preovul atory LH surge. In addition, there was a reduction of the duration of the L H surge (3 +/- 0.1 days in controls vs. 2.1 +/- 0.2 days in treated animals ). The present results show for the first time that there are significant v ariations in plasma levels of SP, with a strong negative correlation with s erum levels of E-2 during the follicular phase of the cynomolgus monkey, an d that endogenous SP has a potentiating role in the interactive hypothalamo -anterior-pituitary mechanisms which lead to the preovulatory LH and FSH su rges during the menstrual cycle in the monkey. Copyright (C) 2000 S. Karger AG, Basel.