Expression of liver prolactin (PRLR), growth hormone (GHR) receptors and sexually dimorphic GH-dependent genes in three mouse models with different levels of GH and PRL.

RAMIREZ, M.C.; PEREZ- MILLÁN, M.I.; ORNSTEIN, A.M.; BECÚ-VILLALOBOS,D.

Boston

Congreso; The Endocrine Society´s 93 rd Annual Meeting; 2011

The Endocrine Society

Pituitary GH secretion is sexually differentiated in many species and sexually dimorphic plasma GH profiles regulate the sex-dependent expression of a large number of liver-expressed genes, including many receptors, signaling molecules, and enzymes of steroid and drug metabolism, especially cytocrome P450s (CYPs). On the other hand, prolactin may impact on liver gene expression; therefore we sought to establish the expression of liver sexually dimorphic genes in three mouse models with different GH and prolactin profiles. Dopaminergic D2 receptor (D2R) knockout mice Drd2-/- have an altered GHRH-GH axis and are growth restricted; besides they have chronic hyperprolactinemia. We also worked with the pituitary conditioned Drd2-/- knockout mice with D2R disruption in lactotropes (lacDrd2-/-) obtained in our laboratory by Cre/LoxP technology; these mice have a conserved GH axis and chronic hyperprolactinemia. Finally, we analysed neonatally androgenized female mice (TP females), which have increased GH and lower prolactin pituitary content compared to control females. We analysed by real-time PCR the mRNA expression of PrlR, GhR, Cyp2b9, Cyp2a4, Cyp2d9 and Mup 1/2/6/8 in the livers of the three mouse models. We found that in both knockout models PrlR mRNA expression was higher in females compared to males, and that it was increased in Drd2-/- and lacDrd2-/- females compared with WT females. There was a significant linear correlation between plasma prolactin levels and liver PrlR mRNA expression (p=0.00094). Conversely, in TP females PrlR mRNA levels were lower than in control females. Male specific expression was confirmed for Cyp2d9 and Mup 1/2/6/8 mRNAs, (male/female ratios of 6.4 and 2.4, respectively, while Cyp2a4 and Cyp2b9 mRNAs were both expressed predominantly in female mice livers (female/male ratios were 7.7 and 11.6, respectively). These genes were not influenced by genotype. On the other hand, Mup 1/2/6/8 mRNA levels were lower in Drd2-/- mice but not in lacDrd2-/- mice. The expression of GhR mRNA was sex-independent and not altered in any of the three models. We conclude that elevated serum prolactin induces the liver expression of its receptor, irrespective of GH levels. On the other hand Mup 1/2/6/8 mRNA expression was more susceptible to GH alterations than the rest of sexually dimorphic GH dependent liver genes in our models.