CONICET | Buscador de Institutos y Recursos Humanos

An altered secretion of LH/hCG has been related to many pathologiesof the hypothalamic-pituitary-gonadal axis. Transgenic femalemice expressing hCGβ subunit (hCGβ+) produce elevated levelsof hCG, prolactin, progesterone and testosterone, are infertile,obese, and develop pituitary and mammary tumors in adulthood.We have previously demonstrated that a short-term treatment ofjuvenile hCGβ+ females with the dopamine agonist cabergoline isable to normalize the phenotypic changes of hCGβ+ females and torecover fertility in adulthood, even in the presence of high levels ofhCG. The aim of this study was to analyze the possible influence ofthe maternal environment (hCG and/or the cabergoline treatment)on the hypothalamic-pituitary-gonadal axis of both transgenic andnontransgenic offspring. Three-week-old wild-type (WT) or hCGβ+females were treated with cabergoline (500 μg/dose) every otherday for one week. In adulthood, these females were crossbred withhCGβ+ or WT males, respectively, and the offspring phenotype wasanalyzed at 3 weeks of age. The phenotype of hCGβ+ offspring derivedfrom cabergoline-treated hCGβ+ females was normalized, interms of serum hormone profile and ovarian gene expression of Lhcgr,Cyp11a1, Cyp17a1 and Cyp19a1. Furthermore, the estrous cycles were regular and the mice were fertile. No changes were found in nontransgenic littermates. In order to define if these findings were due to hCG or to long-lasting effects of cabergoline during gestation, we crossbred cabergoline-treated WT females x hCGβ+ males. Surprisingly,the phenotype of transgenic hCGβ+ offspring was normalized as well. These results showed that a short-term treatment withcabergoline applied prior to the active reproductive age preventedphenotypic alterations on the offspring. It remains to be investigatedif other conditions with altered gonadotropin secretion may also beprevented by cabergoline treatment, as well as the possible epigeneticmechanisms involved.