A potential role of modulating inositol 1,4,5-trisphosphate receptor desensitization and recovery rates in regulating ovulation.
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 (IP3) 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 IP3 receptors to IP3. 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).
Tien
Joseph H
JH
Center for Applied Mathematics, Cornell University, 657 Frank HT Rhodes Hall, Ithaca, NY 14853, USA. joetien@cam.cornell.edu
Lyles
Danielle
D
Zeeman
Mary Lou
ML
D015220:Calcium Channels / Q000502:physiology*; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle / Q000502:physiology; D008954:Models, Biological; D010060:Ovulation / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D007986:Luteinizing Hormone