Abstract
OBJECTIVE: In adult female rodents, ovarian estradiol (E(2)) regulates body weight, adiposity, energy balance, physical activity, glucose-insulin homeodynamics, and lipid metabolism, while protecting against diet-induced obesity. The same E(2) actions are presumed to occur in primates, but confirmatory studies have been lacking. METHODS: We investigated the consequences of ovariectomy (OVX) and E(2) replacement in female marmoset monkeys on major metabolic and morphometric endpoints. Sexual behavior and uterine diameters were assessed as positive controls for E(2) treatment efficacy. Metabolic parameters were measured 1 mo prior to OVX, and 3 and 6 mo thereafter. During OVX, animals received empty or E(2)-containing silastic s.c. implants. To test the interaction between E(2) and diet, both treatment groups were assigned to either a higher fat diet (HFD) or a low-fat diet (LFD). RESULTS: As anticipated, OVX animals exhibited diminished frequency (p = 0.04) of sexually receptive behavior and increased rejection behavior (p = 0.04) toward their male partners compared with E(2)-treated OVX females. OVX also decreased (p = 0.01) uterine diameter. There were no treatment effects on total caloric intake. There were no significant effects of OVX, E(2) treatment, or diet on body weight, body composition, energy expenditure, physical activity, fasting glucose, or glucose tolerance. Regardless of E(2) treatment, serum triglycerides were higher (p = 0.05) in HFD than LFD females. Postmortem qPCR analysis of hypothalamic tissues revealed higher mRNA expression (p < 0.001) for PGR in E(2)-treated monkeys versus OVX controls regardless of diet, but no differences between groups in other selected metabolic genes. In contrast, regardless of E(2) treatment, there was a decreased mRNA expression of PGC1α (PPARGC1A), HTR1A, and HTR5A in HFD compared with LFD females. CONCLUSIONS: Our findings, overall, document a greatly diminished role for ovarian E(2) in the metabolic physiology of a female primate, and encourage consideration that primates, including humans, evolved metabolic control systems regulated by extra-ovarian E(2) or are generally less subject to E(2) regulation.