Minireview: genetic models for the study of gonadotropin actions

Fertility in both sexes relies on complex physiological and molecular processes with many levels of regulation, and our ability to alter the mammalian genome using transgenic technology has greatly enhanced our understanding of these processes. There are numerous commonalities in human and mouse physiology, and the list of mouse models recapitulating recognized and idiopathic human reproductive defects is growing at an ever-increasing rate. In this review, we focus on genetic models of gonadotropin actions, summarizing features of transgenic mice that phenocopy defects in gonadotropin production and gonadotropin receptor responses seen in patients. In addition, we provide examples of mouse models with genetic alterations influencing pituitary FSH and LH production and their effects. These include: 1) transgenic mice with aberrations in steroid hormone, inhibin, and activin feedback pathways; 2) knockouts that demonstrate specific in vivo functions of pituitary transcription factors; and 3) models with alterations in other pituitary hormones, IGF-1, and leptin signaling pathways, which affect both the central and peripheral endocrine axis. What we have to learn from these and other models will continue to revise our conceptions of physiology, identify new targets for contraception, and improve our tools for understanding, diagnosing, and treating cases of human endocrinopathies and pathologies of the reproductive tissues.