Schlosser, Selgrade, 2000

Model Status

This CellML model runs in OpenCell to recreate the pubslihed results. The model also runs in COR but due to the time unit being days the model is not ideal for simulation in COR (where the default unit of time is ms). The units have been checked and they are consistent. The LH system (eq 1a-1e) and the FSH system (eq 2a-2e) are both described in this CellML model. Parameter values have been taken from tables 1 and 2 in the original published paper. We were unable to represent the time delays in equations 1c and 2c.

Model Structure

Abstract: Increasing concerns that environmental contaminants may disrupt the endocrine system require development of mathematical tools to predict the potential for such compounds to significantly alter human endocrine function. The endocrine system is largely self-regulating, compensating for moderate changes in dietary phytoestrogens (e.g., in soy products) and normal variations in physiology. However, severe changes in dietary or oral exposures or in health status (e.g., anorexia) , can completely disrupt the menstrual cycle in women. Thus, risk assessment tools should account for normal regulation and its limits. We present a mathematical model for the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in women as a function of estrogen, progesterone, and inhibin blood levels. The model reproduces the time courses of LH and FSH during the menstrual cycle and correctly predicts observed effects of administered estrogen and progesterone on LH and FSH during clinical studies. The model should be useful for predicting effects of hormonally active substances, both in the pharmaceutical sciences and in toxicology and risk assessment.

Schematic diagram of the mathematical model of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and release. Solid arrows represent pathways of synthesis (syn), release into the blood (rel), and clearance from the blood (clear). Dashed arrows represent regulatory pathways, either positive (+) or negative (-), with feedback from estradiol (E2), progesterone (P4), and inhibin (Ih).

The original paper reference is cited below:

A model of gonadotropin regulation during the menstrual cycle in women: qualitative features Paul M. Schlosser and James F. Selgrade, 2000, Environmental Health Perspectives, 108, 873-881. PubMed ID: 11226623