Schlosser, Selgrade, 2000

Model Status

This CellML version of the model has been checked in COR and PCEnv. The units are consistent and the model runs to recreate the published results.

Model Structure

There are increasing concerns that environmental pollutants may disrupt the endocrine systems in both humans and wildlife. Of particular concern are compounds that can mimic the effects of endogenous estrogen. These can bind to the estrogen receptor and therefore they are able to anatagonise the effects of endogenous estrogen by preventing its binding to its receptor. It has been suggested that artificial estrogens in the environment are responsible for declining male sperm counts and also increases in the incidence of breast cancer. However, there is considerable uncertainty surrounding these hypotheses.

The aim of the study by Schlosser and Selgrade was to develop a mathematical model of the human menstrual cycle which could be used to predict the effects of interactions between exogenous compounds and the sexual endocrine system in adult women. Such a model had to take into consideration the fact the endocrine system is largely self-regulating, and is able to compensate for moderate variations - such as in dietary phytoestrogens (e.g. in soy products), or physiological fluctuations in hormone levels over the course of the menstrual cycle.

The model presented here (and summarised in the figure below) describes the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and their regulation under normal physiological conditions in adult, cycling women. Two systems of two-dimensional ordinary differential equations are used to model the LH and FSH processes of synthesis, release and clearance. Each system is a two compartment model consisting of the hypothalamus/pituitary and the blood as shown in the figure below. Hormone synthesis occurs in the pituitary where the hormones are held in a reserve pool (RP) until they are released into the systemic circulation. Feedback loops are incorporated into the model to capture the various inhibiting and enhancing effects of progesterone (P4) and estradiol (E2) on the synthesis and release of LH and FSH.

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 complete 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. (A full text HTML version of the article is available free on the Environmental Health Perspectives website.) PubMed ID: 11226623