Introduction

Schally isolated and sequenced the decapeptide gonadotrophin releasing hormone (GnRH) in 1971 and demonstrated that it was responsible for the control of the release of two hormones from the pituitary gland: luteinising hormone (LH) and follicle-stimulating hormone (FSH). The mechanism whereby GnRH controls the release of these two gonadotrophins will be the subject of this article.

It has long been realised that anterior pituitary hormones are secreted in diurnal rhythms, but only during the last 15 years has the pulsatile nature of the secretion of these hormones been appreciated. It is the pulsatile release and the modulation of pulse frequency and amplitude, that is fundamental to their biological action. However, the continuous basal secretion of these hormones is probably also significant.

The GnRH gene

Recent experiments in the hypogonadal mouse have revealed that this animal has a 33 kilobase deletional mutation which involves the GnRH gene (Masin et al, 1986). This GnRH gene has been synthesised and replaced into hypogonadotrophic mouse embryos (Mason et al, 1986). Such transgenic mice have full reproductive capability and GnRH expression restored in the appropriate hypothalamic neurones. The unusual feature of this model is that it does not appear to be important where the GnRH gene is replaced in the mouse genome. The clinical parallel of Kallman syndrome to the hypogonadal mouse model is interesting, and may provide a new potential treatment modality.

The human GnRH gene has now been sequenced (Nikolics et al, 1985). As well as a sequence coding for the decapeptide GnRH, there is an area coding for a 56 amino acid peptide, Gonadotrophin Associated Peptide (GAP).