Evolution of gonadotropin signaling on gonad development: insights from gene knockout studies in zebrafish.

Gonadal development is precisely regulated by the two gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Much progress on understanding the functions of LH and FSH signaling on gonad development has been achieved in the past decades, mostly from studies in mammals, especially genetic studies in both mouse and human. The functions of both LH and FSH signaling in nonmammalian species are still largely unknown. In recent years, using zebrafish, a teleost phylogenetically distant from mammals, we and others have genetically analyzed the functions of gonadotropins and their receptors through gene knockout studies. In this review, we will summarize the pertinent findings and discuss how the actions of gonadotropin signaling on gonad development have evolved during evolution from fish to mammals.

Mutations along the pituitary-gonadal axis affecting sexual maturation: novel information from transgenic and knockout mice.

During the last 10 years, numerous activating and inactivating mutations have been detected in the genes encoding the two gonadotrophins, luteinising hormone (LH) and follicle-stimulating hormone (FSH), as well as their cognate receptors (R), LHR and FSHR. Because activation of the hypothalamic-pituitary-gonadal axis is a crucial event in the onset and progression of puberty, mutations affecting gonadotrophin action have major influence on this developmental process. Many of the phenotypic effects observed have been expected on the basis of the existing information about gonadotrophin action (e.g. delayed puberty), but also many unexpected findings have been made, including the lack of phenotype in women with activating LHR mutations, and the discrepancy in phenotypes of men with inactivating mutations of FSHbeta (azoospermia and infertility) and FSHR (oligozoospermia and subfertility). Some of the possible mutations, such as inactivating LHbeta and activating FSHR mutations in women, have not yet been detected. Genetically modified mice provide relevant phenocopies for the human mutations and serve as good models for studies on molecular pathogenesis of these conditions. They may also predict phenotypes of the mutations that have not yet been detected in humans. We review here briefly the effects of gonadotrophin subunit and receptor mutations on puberty in humans and contrast the information with findings on genetically modified mice with similar mutations.