Hemizygous females are not fertile and hemizygous males are sub-fertile. Hemizygotes hypersecrete luteinizing hormone (LH) from pituitary gonadotropes under hypothalamic control. Inclusion of a bovine luteinizing hormone beta (LHB) sequence in the transgene results in a longer hormone half-life. Transgenic females display a range of reproductive and endocrine anomalies, while males are largely phenotypically normal. Transgenic males do not have elevated serum LH or testosterone when compared to wildtype animals, although their testes are significantly smaller. Transgenic females display elevated serum LH, androgens, and estrogens, with subsequent phenotypes including infertility with chronic anovulation and ovarian pathologies ranging from ovarian cysts to strain-dependent granulosa and theca-interstitial cell tumors. Tumors have been noted in mice from age 4 to 9 months. Other major phenotypes include hyperandrogenemia and precocious puberty, defects in uterine receptivity and mid-gestation pregnancy failure, increased oocyte congression failure, adrenocortical hyperfunction, increased central obesity, pituitary adenomas, mammary gland hyperplasia, cancer predisposition, and renal abnormalities (enlarged bladders, dilated ureters, hydronephrosis, nephritis).<br> In humans, LH hypersecretion is implicated in infertility, miscarriages, and development of granulosa cell tumors. This transgenic mouse is a unique model that permits the study of underlying mechanisms of LH toxicity as female transgenic animals display similar reproductive and endocrine pathologies. The female is a model of functional ovarian hyperstimulation, and displays many of the specific endocrine attributes of polycystic ovarian syndrome (PCOS), granulosa cell tumor formation, and central precocious puberty.
