Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion.
Transgenic (TG) female mice, expressing a chimeric bovine luteinizing hormone (LH) beta-subunit/human chorionic gonadotropin beta-subunit COOH-terminal extension (bLHbeta-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 bLHbeta-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 bLHbeta-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 bLHbeta-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 steroidogenesis. Hence, the bLHbeta-CTP mice provide a useful model for studying obesity related to elevated LH secretion, with consequent alterations in ovarian and adrenal function.
Kero
Jukka T
JT
Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Savontaus
Eriika
E
Mikola
Maarit
M
Pesonen
Ullamari
U
Koulu
Markku
M
Keri
Ruth A
RA
Nilson
John H
JH
Poutanen
Matti
M
Huhtaniemi
Ilpo T
IT
D000818:Animals; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000502:physiology; D005260:Female; D017588:Hyperandrogenism / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000254:growth & development / Q000378:metabolism; D023421:Models, Animal; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
D007986:Luteinizing Hormone