Prokai Laszlo, Nguyen Vien, Urbanski Henryk F
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center at Fort Worth, TX, 76063, USA.
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, 97006, USA.
Biochem Biophys Rep. 2023 Sep 16;35:101548. doi: 10.1016/j.bbrep.2023.101548. eCollection 2023 Sep.
Replacement involving estrogens has proven efficacy at treating a wide range of disorders that develop with menopause or after surgical removal of the ovaries. Here, we tested whether an estradiol (E2) replacement paradigm that recapitulates physiological E2 levels in the circulation also recapitulates physiological E2 levels within the hippocampus. E2 was delivered continuously to old ovariectomized (OVX) rhesus macaques, maintained on a high-fat, high-sugar Western-style diet (WSD) for ∼30 months, via subcutaneous implants; this resulted in physiological concentrations of both estrone (E1) and E2 in the circulation (determined by LC-MS/MS). Surprisingly, however, hippocampal concentrations of E2 were markedly ( < 0.01) higher than in ovary-intact animals maintained on a regular chow diet. The data suggest that E2 replacement paradigms that appear to recapitulate physiological E2 concentrations in the circulation may produce hyper-physiological E2 levels within some brain areas, especially when individuals are maintained on a WSD.
雌激素替代疗法已被证明在治疗多种与更年期或卵巢手术切除后出现的疾病方面具有疗效。在此，我们测试了一种模拟循环中生理雌激素水平（E2）的雌二醇替代模式是否也能模拟海马体内的生理雌激素水平。通过皮下植入物，将E2持续给予长期（约30个月）维持高脂高糖西式饮食（WSD）的老年去卵巢（OVX）恒河猴；这导致循环中雌酮（E1）和E2的浓度达到生理水平（通过液相色谱-串联质谱法测定）。然而，令人惊讶的是，海马体中的E2浓度显著高于（<0.01）维持常规饲料饮食的完整卵巢动物。数据表明，看似能模拟循环中生理E2浓度的E2替代模式可能会在某些脑区产生超生理水平的E2，尤其是当个体维持西式饮食时。
