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A potential role of modulating inositol 1,4,5-trisphosphate receptor desensitization and recovery rates in regulating ovulation

Authors
Journal
Journal of Theoretical Biology
0022-5193
Publisher
Elsevier
Publication Date
Volume
232
Issue
1
Identifiers
DOI: 10.1016/j.jtbi.2004.08.003
Keywords
  • Calcium Oscillations
  • Menstrual Cycle
  • Receptor Down-Regulation
  • Lh Surge
  • Mathematical Model

Abstract

Abstract Regulation of the human menstrual cycle is a frequency dependent process controlled in part by the pulsatile release of gonadotropin releasing hormone (GnRH) from the hypothalamus. The binding of GnRH to gonadotroph cells in the pituitary stimulates inositol 1,4,5-trisphosphate (IP 3 ) mediated release of calcium from the endoplasmic reticulum, resulting in calcium oscillations and the secretion of luteinizing hormone (LH). A sudden increase in serum LH concentrations known as the LH surge triggers ovulation. Here we model the intracellular calcium dynamics of gonadotroph cells by adapting the model of Li and Rinzel (J. Theor. Biol. 166 (1994) 461) to include the desensitization of IP 3 receptors to IP 3 . Allowing the resensitization rate of these receptors to vary over the course of the cycle suffices to explain the LH surge in both the normal menstrual cycle, and in the treatment of Kallmann's syndrome (a condition where endogenous production of GnRH is absent).

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