Endocrine Abstracts

The main functions of the two pituitary gonadotrophic hormones, luteinising hormone (LH) and follicle stimulating hormone (FSH), and of the placental choriongonadotropin (hCG), are well characterized today. In clinical medicine, gonadotrophin measurements in peripheral serum form a valuable tool in the diagnosis of disorders in sexual development and fertility, and gonadotrophins are the mainstay in infertility treatments. A great deal of the new information about physiology and pathophysiology of gonadotrophin secretion and actions has emerged from mutations detected in the genes of gonadotropins and their cognate receptors (R), as well as from genetically modified mouse models. The recent detection of gonadotrophin actions in extragonadal tissues both in humans and experimental animals is a topic of continuing controversy. The contributions of our laboratory to this new information include the detection of an inactivating mutation of FSHR and a functionally significant polymorphism in the LHbeta gene. We have also produced a knockout mouse for LHR, and transgenic mice overproducing hCG and expressing a constitutively activated mutant of FSHR. Our findings have clarified some of the controversies surrounding the extragonadal gonadotrophin actions. Our current research is concerned with gonadotrophin physiology and pathophysiology using a variety of genetically modified mouse models now at our disposal. Our key findings include the following: Neither the physiological high intratesticular testosterone concentration nor FSH action are necessary for the induction of spermatogenesis, extragonadal LHR expression is not necessary for the maintenance of female mouse fertility, and homodimerisation of LHR molecules is a physiologically important mode of their action. Whereas a constitutively activating mutation of FSHR induces a dramatic phenotype in the female, the consequences of such a mutation in the male are surprisingly mild. The recent developments in the field indicate that gonadotrophin function will remain in the focus of research in reproductive endocrinology.