title: Mathematical model of FSH-induced cAMP production in ovarian follicles.
abstract: During the terminal part of their development, ovarian follicles become totally dependent on gonadotropin supply to pursue their growth and maturation. Both gonadotropins, follicle-stimulating hormone (FSH) and luteining hormone (LH), operate mainly through stimulatory G protein-coupled receptors, their signal being transduced by the activation of the enzyme adenylyl cyclase and the production of second-messenger cAMP. In this paper, we develop a mathematical model of the dynamics of the coupling between FSH receptor stimulation and cAMP synthesis. This model takes the form of a set of nonlinear, ordinary differential equations that describe the changes in the different states of FSH receptors (free, bound, phosphorylated, and internalized), coupling efficiency (activated adenylyl cyclase), and cAMP response. Classical analysis shows that, in the case of constant FSH signal input, the system converges to a unique, stable equilibrium state, whose properties are here investigated. The system also appears to be robust to nonconstant input. Particular attention is given to the influence of biologically relevant parameters on cAMP dynamics.
authors.affiliation: Institut National de Recherche en Informatique et Automatique, Unité de Recherche de Rocquencourt, Domaine de Voluceau, Rocquencourt, 78153 Le Chesnay Cedex, France. Frederique.Clement@inria.fr
authors.forename: F
authors.initials: F
authors.lastname: Clément
authors.forename: D
authors.initials: D
authors.lastname: Monniaux
authors.forename: J
authors.initials: J
authors.lastname: Stark
authors.forename: K
authors.initials: K
authors.lastname: Hardy
authors.forename: J C
authors.initials: JC
authors.lastname: Thalabard
authors.forename: S
authors.initials: S
authors.lastname: Franks
authors.forename: D
authors.initials: D
authors.lastname: Claude
mesh_terms: D000465:Algorithms; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D008962:Models, Theoretical; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011962:Receptors, FSH / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP