Bulletin of Mathematical Biology

, Volume 70, Issue 8, pp 2211–2228

A Mathematical Model for the Actions of Activin, Inhibin, and Follistatin on Pituitary Gonadotrophs

Authors

    • Department of Mathematics and Programs in Neuroscience and Molecular BiophysicsFlorida State University
  • Yue-Xian Li
    • Department of MathematicsUniversity of British Columbia
Original Article

DOI: 10.1007/s11538-008-9341-2

Cite this article as:
Bertram, R. & Li, Y. Bull. Math. Biol. (2008) 70: 2211. doi:10.1007/s11538-008-9341-2

Abstract

The timed secretion of the luteinizing hormone (LH) and follicle stimulating hormone (FSH) from pituitary gonadotrophs during the estrous cycle is crucial for normal reproductive functioning. The release of LH and FSH is stimulated by gonadotropin releasing hormone (GnRH) secreted by hypothalamic GnRH neurons. It is controlled by the frequency of the GnRH signal that varies during the estrous cycle. Curiously, the secretion of LH and FSH is differentially regulated by the frequency of GnRH pulses. LH secretion increases as the frequency increases within a physiological range, and FSH secretion shows a biphasic response, with a peak at a lower frequency. There is considerable experimental evidence that one key factor in these differential responses is the autocrine/paracrine actions of the pituitary polypeptides activin and follistatin. Based on these data, we develop a mathematical model that incorporates the dynamics of these polypeptides. We show that a model that incorporates the actions of activin and follistatin is sufficient to generate the differential responses of LH and FSH secretion to changes in the frequency of GnRH pulses. In addition, it shows that the actions of these polypeptides, along with the ovarian polypeptide inhibin and the estrogen-mediated variations in the frequency of GnRH pulses, are sufficient to account for the time courses of LH and FSH plasma levels during the rat estrous cycle. That is, a single peak of LH on the afternoon of proestrus and a double peak of FSH on proestrus and early estrus. We also use the model to identify which regulation pathways are indispensable for the differential regulation of LH and FSH and their time courses during the estrous cycle. We conclude that the actions of activin, inhibin, and follistatin are consistent with LH/FSH secretion patterns, and likely complement other factors in the production of the characteristic secretion patterns in female rats.

Keywords

Mathematical modelOvarian cycleEstrous cycleHormone rhythmsGonadotroph

Copyright information

© Society for Mathematical Biology 2008