Borg W, Shackleton C H, Pahuja S L, Hochberg R B
Yale University School of Medicine, Department of Obstetrics and Gynecology, New Haven, CT.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1545-9. doi: 10.1073/pnas.92.5.1545.
Over the past decade it has become increasingly clear that steroid hormones are enzymatically esterified with fatty acids. These steroidal esters are the natural analogs of synthetic esters that are used therapeutically. One such family of pharmacological steroids is the synthetic alkyl esters of testosterone, androgens with great hormonal potency. We have investigated whether testosterone esters exist naturally by using the rat as a model. Most tissues of male rats, including blood, have very little if any ester (quantified by immunoassay as a nonpolar saponifiable metabolite), but fat and testes have sizable quantities, approximately 3 ng of testosterone equivalents per g of tissue. Testosterone in fat averages 9 ng/g. The fat from female rats and long-term (> 2 weeks) castrated males has no detectable testosterone ester. The presence of testosterone esters was confirmed by GC/MS, which clearly showed the presence of testosterone in the hydrolyzed ester fraction of fat from intact males but not long-term castrates. Upon castration, testosterone levels in the fat completely disappear within 6 hr. To the contrary, it is not until 48 hr after castration that a measurable fall in the testosterone ester fraction was observed; even after 10 days a small amount of ester is still present in the fat. These experiments demonstrate the existence of a previously unknown androgen with a potentially important physiological impact; testosterone esters, natural analogs of potent therapeutic agents, occur in the fat where they can serve as a reservoir of preformed androgen to stimulate neighboring target tissues.
在过去十年中，越来越明显的是，甾体激素会与脂肪酸发生酶促酯化反应。这些甾体酯是用于治疗的合成酯的天然类似物。一类这样的药理甾体是睾酮的合成烷基酯，即具有强大激素效力的雄激素。我们以大鼠为模型研究了睾酮酯是否天然存在。雄性大鼠的大多数组织，包括血液，即使有酯（通过免疫测定法将其量化为非极性可皂化代谢物）含量也非常少，但脂肪和睾丸中有相当数量的酯，每克组织中约有3纳克睾酮当量。脂肪中的睾酮平均含量为9纳克/克。雌性大鼠和长期（>2周）去势雄性大鼠的脂肪中未检测到睾酮酯。通过气相色谱/质谱联用仪（GC/MS）证实了睾酮酯的存在，该仪器清楚地显示完整雄性大鼠脂肪水解酯部分中存在睾酮，而长期去势大鼠的脂肪中则没有。去势后，脂肪中的睾酮水平在6小时内完全消失。相反，直到去势后48小时才观察到睾酮酯部分有可测量的下降；即使在10天后，脂肪中仍存在少量酯。这些实验证明了一种以前未知的雄激素的存在，其可能具有重要的生理影响；睾酮酯作为强效治疗剂的天然类似物，存在于脂肪中，可作为预先形成的雄激素储备，以刺激邻近的靶组织。
