Speaker: Dr.Yue-Xian Li (Professor of the University of British Columbia)　
Host: Prof. Runsheng Chen (Center for Computational and Systems Biology)
Time: 3:30 - 4:30pm, July 16th, 2009, Thursday 
Location: Small lecture hall, IBP

 

Abstract:

Reproduction in mammals is controlled by the pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus with a species-specific period of about one hour. Revealing the mechanism underlying the origin of this rhythm has profound consequences in treating developmental and reproductive diseases and in improving human health. Although numerous experimental models have been developed including cultured hypothalamic tissues, placode-derived GnRH neurons, and GT1 cell lines, no well-accepted explanation has been found.

About 800~2000 GnRH neurons participate in the pulse generation. Their cell bodies are distributed in a scattered manner in designated areas of the hypothalamus. Synchronization between these neurons is absolutely necessary for the generation of the hourly pulses of GnRH. How could scattered neurons synchronize their activities remains an unresolved puzzle.

Experiments in the GT1 cells in culture revealed that GnRH neurons express GnRH receptors that allow GnRH to regulate its own secretion through an autocrine effect. GnRH-binding to its receptors on the GnRH neurons triggers the activation of three types of G-proteins of which two activates and one inhibits GnRH secretion (Krsmanovic et al, 2003, PNAS 100:2969). Based on this mechanism, GnRH secreted by GnRH neurons serve as a diffusive mediator as well as an autocrine regulator. A mathematical model is developed (Khadra-Li, 2006, Biophys. J. 91:74) and its robustness and potential applicability to GnRH neurons in vivo is investigated (Li-Khadra, 2008, BMB 70:2103). In this talk, I will introduce the key experimental and modeling results on this system including more recent results that are not yet published. These include the extension of the previous models to the case of diffusely distributed GnRH neurons coupled by a diffusive GnRH signal. Based on these results, one plausible explanation for why GnRH neurons are distributed in a scattered way is proposed.

 

Li_CV4PR_Jul09.pdf