A mathematical model of luteinizing hormone release from ovine pituitary cells in perifusion

We model the effect of gonadotropin-releasing hormone (GnRH) on the product ion of luteinizing hormone (LH) by the ovine pituitary. GnRH, released by t he hypothalamus, stimulates the secretion of LH from the pituitary. If stim ulus 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 (t ermed desensitization). The proposed mathematical model consists of a syste m of nonlinear differential equations and incorporates two possible mechani sms to account for this observed behavior: desensitized receptor and Limite d, available LH. Desensitization was provoked experimentally in vitro by us ing ovine pituitary cells in a perifusion system. The model was fit to resu lting experimental data by using maximum-likelihood estimation. Considerati on of smaller models revealed that the desensitized receptor is significant . Limited, available LH was significant in three of four chambers. Througho ut, the proposed model was in excellent agreement with experimental data.