Gonadotrophin-releasing hormone deficiency in a mutant mouse with hypogonadism

The genetic and endocrinological background of a mutant strain of mouse in which the testes and ovaries fail to develop postnatally is reported, which should prove useful for studying the synthesis of hypothalamic releasing hormones as well as the role of the hypothalamic–gonadotrophin system in sexual differentiation, puberty, folliculogenesis and spermatogenesis.

Abstract

FAMILIAL hypogonadism in man, due to an isolated deficiency of gonadotrophin secretion, has been well documented1–6, but difficult to investigate because of the lack of a suitable animal model4. We report here the genetic and endocrinological background of a mutant strain of mouse in which the testes and ovaries fail to develop postnatally. The primary cause of this seems to be a deficiency in hypothalamic gonadotrophin-releasing hormone (GnRH) with a consequent reduction in pituitary content and circulating levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH). By analogy with the Brattleboro rat (genetic defect in vasopressin synthesis) this mutant should prove useful for studying the synthesis of hypothalamic releasing hormones as well as the role of the hypothalamic–gonadotrophin system in sexual differentiation, puberty, folliculogenesis and spermatogenesis. The mutant has been named hypogonadal, symbol hpg.