Hyperprolactinemia induced by hCG leads to metabolic disturbances in female mice

• Published in: Journal of endocrinology Vol. 230; no. 1; pp. 157 - 169
• Main Authors: Ratner, Laura D, Stevens, Guillermina, Bonaventura, Maria Marta, Lux-Lantos, Victoria A, Poutanen, Matti, Calandra, Ricardo S, Huhtaniemi, Ilpo T, Rulli, Susana B
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01-07-2016
• Subjects: Animals; Blood Glucose - metabolism; Chorionic Gonadotropin, beta Subunit, Human - genetics; Chorionic Gonadotropin, beta Subunit, Human - metabolism; Ergolines - therapeutic use; Female; Glucose Intolerance - drug therapy; Glucose Intolerance - genetics; Glucose Intolerance - metabolism; Hyperinsulinism - drug therapy; Hyperinsulinism - genetics; Hyperinsulinism - metabolism; Hyperprolactinemia - drug therapy; Hyperprolactinemia - genetics; Hyperprolactinemia - metabolism; Hypertriglyceridemia - drug therapy; Hypertriglyceridemia - genetics; Hypertriglyceridemia - metabolism; Insulin - blood; Insulin Resistance - physiology; Mice; Mice, Transgenic; Prolactin - blood; Triglycerides - blood; prolactin; transgenic mice; human chorionic gonadotropin; insulin resistance
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1530/JOE-15-0528

The metabolic syndrome is a growing epidemic; it increases the risk for diabetes, cardiovascular disease, fatty liver, and several cancers. Several reports have indicated a link between hormonal imbalances and insulin resistance or obesity. Transgenic (TG) female mice overexpressing the human chorionic gonadotropin β-subunit (hCGβ+ mice) exhibit constitutively elevated levels of hCG, increased production of testosterone, progesterone and prolactin, and obesity. The objective of this study was to investigate the influence of hCG hypersecretion on possible alterations in the glucose and lipid metabolism of adult TG females. We evaluated fasting serum insulin, glucose, and triglyceride levels in adult hCGβ+ females and conducted intraperitoneal glucose and insulin tolerance tests at different ages. TG female mice showed hyperinsulinemia, hypertriglyceridemia, and dyslipidemia, as well as glucose intolerance and insulin resistance at 6 months of age. A 1-week treatment with the dopamine agonist cabergoline applied on 5-week-old hCGβ+ mice, which corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, effectively prevented the metabolic alterations. These data indicate a key role of the hyperprolactinemia-induced gonadal dysfunction in the metabolic disturbances of hCGβ+ female mice. The findings prompt further studies on the involvement of gonadotropins and prolactin on metabolic disorders and might pave the way for the development of new therapeutic strategies.