Reproductive axis function and gonadotropin microheterogeneity in a male rat model of diet-induced obesity

• Published in: General and comparative endocrinology Vol. 166; no. 2; pp. 356 - 364
• Main Authors: Olivares, Aleida, Méndez, Juan Pablo, Zambrano, Elena, Cárdenas, Mario, Tovar, Armando, Perera-Marín, Gerardo, Ulloa-Aguirre, Alfredo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2010
• Subjects: Animals; Blood Glucose - analysis; Dietary Fats - administration & dosage; Disease Models, Animal; Endocrinology & Metabolism; Estradiol - blood; Experimental obesity; Glycosylation; High-fat diet; Hydrogen-Ion Concentration; Insulin Resistance; Leptin - blood; LH bioactivity; Luteinizing hormone; Luteinizing Hormone - analysis; Luteinizing Hormone - blood; Luteinizing Hormone - physiology; Male; Metabolic Syndrome; Obesity - etiology; Obesity - physiopathology; Pituitary Gland, Anterior - chemistry; Protein Isoforms - analysis; Rats; Rats, Wistar; Reproduction - physiology; Testosterone - blood; Triglycerides - blood; Luteinizing hormone; LH bioactivity; High-fat diet; Experimental obesity
• ISSN: 0016-6480; 1095-6840
• DOI: 10.1016/j.ygcen.2009.12.007

Abstract Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17β-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99–9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary–testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function.