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This Article Full Text Full Text (PDF) All Versions of this Article: 285/4/E812    most recent 00367.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Kero, J. T. Articles by Huhtaniemi, I. T. Search for Related Content PubMed PubMed Citation Articles by Kero, J. T. Articles by Huhtaniemi, I. T.

Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion

Departments of ¹Physiology, ²Pharmacology and Clinical Pharmacology, and ³Pediatrics, University of Turku, 20520 Turku, Finland; and ⁴Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Submitted 19 August 2002 ; accepted in final form 21 May 2003

Transgenic (TG) female mice, expressing a chimeric bovine luteinizing hormone (LH) -subunit/human chorionic gonadotropin -subunit COOH-terminal extension (bLH-CTP) gene, produce high levels of circulating LH and serve as a model for functional ovarian hyperandrogenism and follicular cysts. We report here that obesity is a typical feature of these female mice. The mean body weight of the bLH-CTP females was significantly higher than in controls at, and beyond 5 wk of age, and at 5 mo, it was 32% increased. At this age, the amount of white adipose tissue in the bLH-CTP females was significantly increased, as reflected by the weight difference of the retroperitoneal fat pad. In addition, the expression of leptin mRNA in white adipose tissue of the TG females was elevated about twofold. Serum leptin and insulin levels, and food intake, were also increased significantly in the TG females. Brown adipose tissue (BAT) thermogenic activity, as measured by GDP binding to BAT mitochondria, was reduced (P < 0.05). Ovariectomy at the age of 3 wk totally prevented the development of obesity. In summary, the present results show that intact female bLH-CTP mice are obese, have increased food consumption, and reduced BAT thermogenic activity. The weight gain can be explained partly by elevated androgens but is probably also contributed to the increased adrenal steroidogeneisis. Hence, the bLH-CTP mice provide a useful model for studying obesity related to elevated LH secretion, with consequent alterations in ovarian and adrenal function.

transgenic mice; polycystic ovarian syndrome; corticosterone; thermogenesis; hyperphagia

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