A Computer Simulation Model for Automated Quantification of Luteinizing Hormone Secretion

Abstract

Problem statement: An automated software package is developed for quantifying Luteinizing Hormone (LH) release from pituitary gonadotropes in response to short pulses of Gonadotropin-Releasing Hormone (GnRH). Approach: These computer programs were designed to accommodate the release mechanism that consists of three stages, namely; (1) Production of different concentrations of effectors (such as receptor-hormone binds, G protein interactions, inositol 1,4,5-trisphosphate IP3), (2) Release of Ca²⁺ from the endoplasmic reticulum ER and finally (3) Release of LH through pumping of Ca²⁺ in and out of the cytosol. Results: The programs were coded in C++ computer language and implemented on Pentium PC. The designed model was intended to help in explaining the characteristics of LH release in response to various duration and different concentrations of GnRH pulses in the presence and absence of external Ca²⁺. Conclusion: Features of the short-term responses were simulated and fairly understood using receptor binding, dimerization, interaction of the dimerized receptor with a G protein, production of effectors that open voltage sensitive channels in cell membrane and finally open the Ca²⁺ channels in the ER and the Ca²⁺-dependent release of LH. Also, prediction of the varying concentrations of Ca²⁺ effects and comparison with experimental data was made possible.