Mechanisms of multiple forms of tumorigenesis in LH/hCG overexpressing transgenic mice

Abstract

The two gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by the pituitary gland as heterodimers composed of a common a-subunit and the hormone- specific b-subunit. They have a key role in ovarian and testicular functions by acting through binding to their specific seven-transmembrane domain G-protein coupled receptors (Burger et al., 2004). In the gonads, LH receptors are located in testicular Leydig cells and in ovarian theca, granulosa and luteal cells (Ascoli et al., 2002). FSH receptors are expressed in testicular Sertoli cells and in granulosa cells of the ovary (Simoni et al., 1997). Although primarily expressed in gonads, LH receptors are also found in numerous extragonadal tissues (Rao, 2001; Filicori et al., 2005). However, their physiological significance is still unclear (Pakarainen et al., 2007). The placental analogue of LH, human chorionic gonadotrophin (hCG) interacts with the same LH/hCG receptor as LH, and functions as an LH agonist with a longer half-life and higher biopotency than its pituitary counterpart (Jameson and Hollenberg,1993).