During the last two decades a large number of genetically modified mouse lines with altered
gonadotropin action have been generated. These mouse lines fall into three categories: the lack-of-function mice, gain-of-function mice, and the mice generated by breeding the abovementioned lines with other disease model lines. The mouse strains lacking
gonadotropin action have elucidated the necessity of the
pituitary hormones in pubertal development and function of gonads, and revealed the processes from the original genetic defect to the pathological phenotype such as hypo- or
hypergonadotropic hypogonadism. Conversely, the strains of the second group depict consequences of chronic
gonadotropin action. The lines vary from those expressing constitutively active receptors and those secreting
follicle-stimulating hormone (FSH) with slowly increasing amounts to those producing human
choriogonadotropin (hCG), amount of which corresponds to 2000-fold
luteinizing hormone (LH)/hCG
biological activity. Accordingly, the phenotypes diverge from mild anomalies and enhanced fertility to disrupted gametogenesis, but eventually chronic, enhanced and non-pulsatile action of both FSH and LH leads to female and
male infertility and/or hyper- and
neoplasias in most of the
gonadotropin gain-of-function mice. Elevated
gonadotropin levels also alter the function of several extra-gonadal tissues either directly or indirectly via increased sex
steroid production. These effects include promotion of
tumorigenesis in tissues such as the pituitary, mammary and adrenal glands. Finally, the crossbreedings of the current mouse strains with other disease models are likely to uncover the contribution of
gonadotropins in novel
biological systems, as exemplified by the recent crossbreed of LHCG receptor deficient mice with
Alzheimer disease mice.