Ovarian estradiol supports sexual behavior but not energy homeostasis in female marmoset monkeys.

Abstract

In adult female rodents, ovarian estradiol (E₂) regulates body weight, adiposity, energy balance, physical activity, glucose-insulin homeodynamics, and lipid metabolism, while protecting against diet-induced obesity. The same E₂ actions are presumed to occur in primates, but confirmatory studies have been lacking. We investigated the consequences of ovariectomy (OVX) and E₂ replacement in female marmoset monkeys on major metabolic and morphometric endpoints. Sexual behavior and uterine diameters were assessed as positive controls for E₂ treatment efficacy. Metabolic parameters were measured 1 mo prior to OVX, and 3 and 6 mo thereafter. During OVX, animals received empty or E₂-containing silastic s.c. implants. To test the interaction between E₂ and diet, both treatment groups were assigned to either a higher fat diet (HFD) or a low-fat diet (LFD). 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 E₂-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, E₂ treatment, or diet on body weight, body composition, energy expenditure, physical activity, fasting glucose, or glucose tolerance. Regardless of E₂ 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 E₂-treated monkeys versus OVX controls regardless of diet, but no differences between groups in other selected metabolic genes. In contrast, regardless of E₂ treatment, there was a decreased mRNA expression of PGC1α (PPARGC1A), HTR1A, and HTR5A in HFD compared with LFD females. Our findings, overall, document a greatly diminished role for ovarian E₂ in the metabolic physiology of a female primate, and encourage consideration that primates, including humans, evolved metabolic control systems regulated by extra-ovarian E₂ or are generally less subject to E₂ regulation.