Mouse models for gonadotropins: A 15-year Saga

Pituitary gonadotropins FSH and LH are heterodimeric glycoproteins consisting of a common alpha and a hormone-specific beta subunit that are non-covalently linked. Both these hormones bind G-protein coupled receptors and regulate multiple processes in the gonads. Advances in the past two decades in manipulating the mouse genome by random and site-specific mutagenesis have been invaluable to our understanding of the biology of gonadotropins. Using these transgenic and gene targeting approaches, both gain-of-function transgenic as well as knockout mice lacking the hormone-specific gonadotropin subunits, and hence functional dimeric hormones were generated. Furthermore, knockout mice lacking regulators of gonadotropin production have also been characterized. These mice are useful to delineate the distinct in vivo biological roles of FSH and LH, and provide valuable genetic tools to study the signaling mechanisms within the gonads. Here, I will discuss our work on different ways to manipulate gonadotropin ligand function in the mouse.