Liver and White Adipose Tissue Gene Expression in Hyperprolactinemic Lactotrope-Drd2KO Mice

GUILLERMINA MARÍA LUQUE; MARÍA INÉS PÉREZ-MILLÁN; MARÍA CECILIA RAMÍREZ; MARÍA FELICITAS LÓPEZ VICCHI; ANA MARÍA ORNSTEIN; MARCELO RUBINSTEIN; DAMASIA BECU-VILLALOBOS

Chicago

Congreso; The Endocrine Society's 96th Annual Meeting & Expo; 2014

Prolactin, a pleiotropic hormone secreted by lactotropes, participates in metabolic processes and acts by binding to its receptor (PRLR). In mice, one long (PRLR-L) and three short receptor forms (PRLR-S1, PRLR-S2, and PRLR-S3) have been identified. We previously found conditional mutant mice that selectively lack D2Rs from pituitary lactotropes (lacDrd2KO) present chronically elevated prolactin levels, increased food intake, adipose tissue accretion, and produced glucose intolerance. We now evaluated the role of elevated prolactin levels on adipose tissue and liver gene expression. LacDrd2KO female mice exhibited chronic hyperprolactinemia, preserved GH axis, increased body weight, and a marked increment in adipocyte size and liver weight. We found that Prlr-l mRNA expression in adipose tissue of female lacDrd2KO mice was similar to that in controls, while the short forms were below the detection limit in this tissue. A decrease in lipolytic enzymes (Atgl and Hsl) was observed in female lacDrd2KO adipose tissue, while GH (Ghr) and glucocorticoid receptor (Gr) mRNA expression showed no change. On the other hand, the liver of lacDrd2KO female mice had increased lipid content as indicated by oil red staining, in accordance with increased triglyceride content. A different Prlr mRNA expression pattern was found in this tissue: Prlr expression level was increased (P<0.01) in the liver of female lacDrd2KO mice compared to controls, and all four mRNAs Prlr isoforms were detected; in particular, the Prlr-s3 isoform was significantly increased. The liver has a central role in glucose homeostasis which may be modulated by serum prolactin; we found that glucokinase mRNA expression was significantly increased (P<0.02) in female lacDrd2KO, while sterol regulatory element binding transcription factor 1 (Srebf1), glycogen synthase 2 (Gys2) and carbohydrate response element binding protein (Chrebp) gene expression were similar to that observed in controls. These results suggest that high prolactin levels may modulate lipid and glucose metabolism. In the liver prolactin upregulates its own receptor and glucokinase expression, while in the adipose tissue it increases lipogenesis by decreasing lipolytic enzymes with no change in Prlr , Ghr or Gr expression.