Abstract：
BACKGROUND: The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized.
OBJECTIVE: We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women.
METHODS: Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n=50) and without (n=13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction.
RESULTS: HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to non-users. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to non-users of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users.
CONCLUSIONS: Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT, and these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity.
OBJECTIVE: We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women.
METHODS: Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n=50) and without (n=13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction.
RESULTS: HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to non-users. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to non-users of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users.
CONCLUSIONS: Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT, and these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity.
摘要：
背景：绝经后血清雌激素的减少与从gynoid到android脂肪组织（AT）分布的转变有关。更年期激素治疗（HT）减轻了这种变化和伴随的代谢功能障碍，但其对AT性类固醇代谢的影响尚未被表征。
目的：我们研究了HT对绝经后妇女皮下和内脏AT雌激素和雄激素浓度及代谢的影响。
方法：分析了63名口服HT（n=50）和无（n=13）的绝经后妇女的血清，皮下和内脏AT，雌二醇,黄体酮,睾丸激素，雄烯二酮,脱氢表雄酮，使用液相色谱-串联质谱法和血清硫酸雌酮。使用放射性标记的前体测量类固醇硫酸酯酶活性。使用实时逆转录定量聚合酶链反应进行编码性类固醇代谢酶和受体的基因的mRNA表达。
结果：HT使用者在皮下和内脏AT中的雌酮和雌二醇浓度高4至7倍，与非使用者相比，内脏AT的睾酮降低了30%。与非HT使用者相比，AT使用者的雌激素与雄激素比率高4至12倍。在内脏AT中，雌激素与雄激素比率随HT雌二醇剂量而增加。HT使用者的雌酮和雌二醇的AT与血清比率仍然很高。
结论：在HT使用者中较高的局部雌激素与雄激素的比率和高的AT与血清雌激素浓度的比率表明HT可能显著影响AT的内分泌性激素代谢，这些局部变化可能与HT对绝经相关腹部肥胖的预防作用有关。
目的：我们研究了HT对绝经后妇女皮下和内脏AT雌激素和雄激素浓度及代谢的影响。
方法：分析了63名口服HT（n=50）和无（n=13）的绝经后妇女的血清，皮下和内脏AT，雌二醇,黄体酮,睾丸激素，雄烯二酮,脱氢表雄酮，使用液相色谱-串联质谱法和血清硫酸雌酮。使用放射性标记的前体测量类固醇硫酸酯酶活性。使用实时逆转录定量聚合酶链反应进行编码性类固醇代谢酶和受体的基因的mRNA表达。
结果：HT使用者在皮下和内脏AT中的雌酮和雌二醇浓度高4至7倍，与非使用者相比，内脏AT的睾酮降低了30%。与非HT使用者相比，AT使用者的雌激素与雄激素比率高4至12倍。在内脏AT中，雌激素与雄激素比率随HT雌二醇剂量而增加。HT使用者的雌酮和雌二醇的AT与血清比率仍然很高。
结论：在HT使用者中较高的局部雌激素与雄激素的比率和高的AT与血清雌激素浓度的比率表明HT可能显著影响AT的内分泌性激素代谢，这些局部变化可能与HT对绝经相关腹部肥胖的预防作用有关。
