Genetically modified mouse models for the study of LH action.

HUHTANIEMI I, AHTIAINEN P, PAKARAINEN T, RULLI S, POUTANEN M.

Boston, USA

Simposio; 88th Annual Meeting of the Endocrine Society; 2006

The Endocrine Society

Numerous genetically modified mouse models have been developed recently for the study of pituitary-gonadal function. Knockout models exist now for GnRH, LH, FSH and their receptors. They offer in most cases good phenocopies of respective mutations observed in humans, and allow experimental studies on the molecular pathogenesis of deficient GnRH or gonadotropin action. In addition, there are now multiple transgenic mouse models overexpressing LH, hCG and FSH, which make it possibly to assess the pathophysiological consequences of chronically elevated gonadotropin levels. The purpose of this presentation is to review some of our recent findings on transgenic mice expressing high levels of hCG as well as on an LHR knockout mouse, totally devoid of LH action. The rather expected gonadal hyper- and hypofunction phenotypes of these two models reconfirm our previous knowledge about the physiological functions of LH/hCG. In addition, several unexpected findings were made, including the induction of multiple gonadal and extragonadal tumors by chronically elevated LH/hCG action. The LHR knockout model clarified to what extent gonadal function is possible in the total absence of LHR activation, and what role extragonadal LHR expression has in mouse reproductive functions. Ovary transplantation experiments in LHR knockout mice demonstrated physiological redundancy of extragonadal LH action for female fertility.