An official journal of the Society for Biology of Reproduction and the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn

March 2014 (No. 1)

Genetically modified mouse models addressing gonadotropin function

Laura D. Ratner a, Susana B. Rulli a,*, Ilpo T. Huhtaniemi b,c

a Instituto de Biología y Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina

b Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu, FIN-20520 Turku, Finland

c Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK

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The development of genetically modified animals has been useful to understand the mecha- nisms involved in the regulation of the gonadotropin function. It is well known that alterations in the secretion of a single hormone is capable of producing profound reproductive abnormal- ities. Human chorionic gonadotropin (hCG) is a glycoprotein hormone normally secreted by the human placenta, and structurally and functionally it is related to pituitary LH. LH and hCG bind to the same LH/hCG receptor, and hCG is often used as an analog of LH to boost gonadotropin action. There are many physiological and pathological conditions where LH/ hCG levels and actions are elevated. In order to understand how elevated LH/hCG levels may impact on the hypothalamic–pituitary–gonadal axis we have developed a transgenic mouse model with chronic hCG hypersecretion. Female mice develop many gonadal and extrago- nadal phenotypes including obesity, infertility, hyperprolactinemia, and pituitary and mam- mary gland tumors. This article summarizes recent findings on the mechanisms involved in pituitary gland tumorigenesis and hyperprolactinemia in the female mice hypersecreting hCG, in particular the relationship of progesterone with the hyperprolactinemic condition of the model. In addition, we describe the role of hyperprolactinemia as the main cause of infertility and the phenotypic abnormalities in these mice, and the use of dopamine agonists bromo- criptine and cabergoline to normalize these conditions.

Reproductive Biology 2014 14 1: 9-15

* Corresponding author: Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina;  e-mail address: (SBR).