title: Inactivating mutations of LH and FSH receptors--from genotype to phenotype.
abstract: The pituitary glycoprotein hormones, LH and FSH, and their receptors are essential for normal reproductive function in both sexes. Over the past 10 years, several inactivating mutations of the gonadotropin receptors have been described in rare forms of human primary gonadal disorders. Homozygous or compound heterozygous inactivating mutations of the LH receptor were associated with a rare autosomal recessive form of male pseudohermaphroditism (Leydig cell hypoplasia), micropenis and hypergonadotropic hypogonadism in genetic males. In addition, these mutations caused primary or secondary amenorrhea and infertility in women who were sisters of male pseudohermaphrodites. Similarly, FSH receptor inactivating mutations were associated with partial or complete phenotypes of premature ovarian failure in women. These inactivating mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. In addition, the characterization of the molecular basis of gonadal resistance can be useful for directing therapy and for genetic counseling.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Disciplina de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. anacl@usp.br
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
authors.forename: Ivo Jorge Prado
authors.initials: IJ
authors.lastname: Arnhold
mesh_terms: D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011962:Receptors, FSH / Q000235:genetics* / Q000502:physiology; D011974:Receptors, LH / Q000235:genetics* / Q000502:physiology
chemical_list: D011962:Receptors, FSH; D011974:Receptors, LH