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 and progesterone secretion in the cycling cynomolgus monkey

Bernard Kerdelhué, Robert F. Williams, Véronique Lenoir, Véronique Fardin, Paul Kolm, Gary D. Hodgen, Georgeanna Seegar Jones, Robert Scholler, Howard W. Jones

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Abstract

These studies investigated the role of substance P (SP) in the regulation of the hypothalamic-pituitary-ovarian axis in cynomolgus monkeys with normal menstrual cycles. Plasma concentrations of SP were determined in blood samples taken every morning in normally menstruating cynomolgus monkeys throughout the menstrual cycle. There was a significant decreasing linear trend of SP during the follicular phase (cycle day -13 to day 0) and a significant inverse relationship between SP plasma values and plasma 17β-estradiol (E2) values from day -13 to day 0 of the adjusted cycle. Correspondingly, SP area under the curve was significantly greater during the follicular phase than the luteal phase. In a second experiment, plasma concentrations of E2, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone and length of cycles were measured after five daily intragastric administrations (10 mg/kg) of an NK1 receptor (SP receptor) antagonist (RPR 100893; 10 mg/kg) initiated after serum E2 concentrations had exceeded 125 pg/ml. There was a statistically significant reduction in the amplitude (41% of control) and the area under the curve (37% of control) of the preovulatory LH surge. In addition, there was a reduction of the duration of the LH 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 variations in plasma levels of SP, with a strong negative correlation with serum levels of E2 during the follicular phase of the cynomolgus monkey, and that endogenous SP has a potentiating role in the interactive hypothalamo-anterior-pituitary mechanisms which lead to the preovulatory LH and FSH surges during the menstrual cycle in the monkey. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)228-236
Number of pages9
JournalNeuroendocrinology
Volume71
Issue number4
DOIs
StatePublished - Jan 1 2000

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Keywords

  • Gonadotropins
  • Monkey
  • Neurokinin receptors
  • Ovulation
  • Substance P antagonists

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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