Modelling the pituitary response to luteinizing hormone-releasing hormone

The pituitary response to luteinizing hormone-releasing hormone (LHRH) is steroid-dependent and varies throughout the reproductive cycle, but the rapid rise in pituitary sensitivity on the day of the ovulation-inducing LH surge is due to a 'self-priming' effect of exposure to LHRH that results in a potentiation of pituitary responsiveness 35-40 min later. The expression of this effect is itself steroid-dependent, and is most marked on pro-oestrus. Here, a model of LHRH-induced LH release was developed to incorporate the changes in pituitary sensitivity observed throughout the reproductive cycle. LH release is based on the Law of Mass Action, and a component related to self-priming is included in the model, incorporating the delay between initial exposure and potentiation of responsiveness and an upper maximum to the achievable level of priming. Where possible, model parameters were obtained from biological values, otherwise they were optimized to fit an experiment performed in vivo. These parameters were then used to test the model against other experimental data obtained both in vivo and in vitro. The model provided a good fit to the in vivo data but the in vitro experimental data required a change in one parameter, the upper limit of priming. We conclude that this model of the pituitary release mechanism can simulate the changes in pituitary responsiveness throughout the reproductive cycle. We suggest that substitution of this model in a previous model of the LHRH pulse generator could allow more appropriate tests of the LHRH pulse generator model.