Producción CyT
Endocrine Reviews - The effect of hyperprolactinemia on glucose and lipid metabolism in a transgenic mouse model with human chorionic gonadotropin (hCG) hypersecretion.
Congreso
Fecha:
2015Editorial y Lugar de Edición:
The Endocrine SocietyISSN:
0163-769XResumen *
The effect of hyperprolactinemia on glucose and lipid metabolism in a transgenic mouse model with human chorionic gonadotropin (hCG) hypersecretion. Laura D. Ratner; Carla A. Marcial; Guillermina Stevens; Matti Poutanen, Ilpo Huhtaniemi, Ricardo S. Calandra; Susana B. Rulli. Transgenic female mice overexpressing the human chorionic gonadotropin β-subunit (hCGβ+) exhibit constitutively elevated levels of hCG, develop hyperprolactinemia, infertility and obesity with the presence of abdominal fat at adulthood. The females show hyperinsulinemia, hypertriglyceridemia, glucose intolerance and insulin resistance at 6 months of age. The aim of this study was to analyze the influence of hyperprolactinemia on the glucose and lipid metabolism in adult hCGβ+ females. To this end, the dopamine agonist, cabergoline was administered to 5-week-old hCGβ+ females every other day (500 µg/kg; vía i.p.) during one week (hCGβ+cab). We have previously demonstrated that this treatment was able to correct hyperprolactinemia and infertility of hCGβ+ females. At six months of age, intraperitoneal glucose tolerance test (IGTT) was performed in mice fasted for 6 hs (2 g/kg glucose, via i.p.), and insulin tolerance test (ITT) was performed after 4 hs fasting (0,75 IU/kg insulin, via i.p.); serum glucose levels were determined at 0, 30, 60 and 90 min post-injection. Cabergoline treatment produced a complete reversion of glucose intolerance and insulin resistance, as determined by normalization of the IGTT and ITT curves, as well as a significant reduction in insulin and triglyceride levels (p<0,001). On the other hand, the gene expression of preproinsulin (Ins-1, Ins-2) and glucagon (Gcg) in pancreas was analyzed by quantitative Real Time PCR. hCGβ+cab females showed a significant decrease in Ins-1 e Ins-2 gene expression levels in comparison to hCGβ+ females (p<0,05), without changes in Gcg. In conclusion, a short-term treatment with cabergoline at young ages effectively prevented the hyperprolactinemia-associated metabolic dysfunctions of hCGβ+ mice, which were manifested at adulthood. These findings provide strong evidence that elevated prolactin levels have a key role for the metabolic alterations in hCG overproducing females. Información suministrada por el agente en SIGEVAPalabras Clave
INFERTILITYHYPERPROLACTINEMIACABERGOLINEHYPERINSULINEMIA