A comprehensive curated resource for follicle stimulating hormone signaling

Abstract

Background: Follicle stimulating hormone (FSH) is an important hormone responsible for growth, maturation and function of the human reproductive system. FSH regulates the synthesis of steroid hormones such as estrogen and progesterone, proliferation and maturation of follicles in the ovary and spermatogenesis in the testes. FSH is a glycoprotein heterodimer that binds and acts through the FSH receptor, a G-protein coupled receptor. Although online pathway repositories provide information about G-protein coupled receptor mediated signal transduction, the signaling events initiated specifically by FSH are not cataloged in any public database in a detailed fashion.

Findings: We performed comprehensive curation of the published literature to identify the components of FSH signaling pathway and the molecular interactions that occur upon FSH receptor activation. Our effort yielded 64 reactions comprising 35 enzyme-substrate reactions, 11 molecular association events, 11 activation events and 7 protein translocation events that occur in response to FSH receptor activation. We also cataloged 265 genes, which were differentially expressed upon FSH stimulation in normal human reproductive tissues.

Conclusions: We anticipate that the information provided in this resource will provide better insights into the physiological role of FSH in reproductive biology, its signaling mediators and aid in further research in this area. The curated FSH pathway data is freely available through NetPath (http://www.netpath.org), a pathway resource developed previously by our group.

Figure 1

An overview of the FSH pathway page in NetPath. The FSH pathway page in NetPath displays the statistics of data in the FSH pathway reactions including the number of proteins, protein-protein interactions, enzyme-substrate reactions, translocation events and differentially regulated genes in normal/primary human cells. The complete list of these reactions is accessible through the specific links provided for each reaction. Brief comments are provided for reactions curated under reactions such as PPI, enzyme-substrate reactions and transport. Each of these molecules is linked to NetPath molecule page which is further linked to Entrez gene, HPRD [30], OMIM [31] and Swiss-Prot [32] identifiers. A list of curators/reviewers is provided in the FSH pathway page with the details of the Pathway Authority. A 'comments' tab is provided in the pathway page to invite queries and suggestions from the community as a means to keep the pathway updated and as error-free as possible.

Figure 2

FSH pathway reaction map generated using CellDesigner. The reactions in the pathway resource were used to obtain a descriptive network of reactions using CellDesigner. The legend for the pathway map is provided in the box to the right. The reactions are broadly arranged according to the cellular component they occur in and are depicted here on the plasma membrane (yellow thick line at the top) and the nucleus (the rectangle with the blue border at the bottom) and the cytosol (the space between the yellow line and the blue rectangle). The small molecules such as cyclic AMP (cAMP), calcium (Ca++), inositol 3-phosphate (IP3) and diacylglycerol (DAG) which are important mediators of FSH signaling are also represented in the map.