Karen Heinze, Ph.D
Postdoctoral Research Fellow
Pharmacokinetics, Dynamics, and Metabolism
2800 Plymouth Road
Ann Arbor, MI 48105
We model the effect of gonadotrophin-releasing hormone (GnRH) on the production of luteinizing hormone (LH) by the ovine pituitary. GnRH, released by the hypothalamus, stimulates the secretion of LH from the pituitary. If stimulus pulses are regular LH response will follow a similar pattern. However, during application of GnRH at high frequencies or concentrations, or with continuous application, the pituitary delivers a decreased release of LH (termed desensitization). The proposed mathematical model consists of a system of nonlinear differential equations and incorporates two possible mechanisms to account for this observed behavior: desensitized receptor and limited, available LH. Desensitization was provoked experimentally in vitro using ovine pituitary cells in a perifusion system. The model was fit to resulting experimental data using maximum likelihood estimation. Consideration of smaller models revealed that the desensitized receptor is significant. Limited, available LH was significant in three of four chambers. Throughout, the proposed model was in excellent agreement with experimental data.