Pashko L L, Schwartz A G
Fels Institute for Cancer Research and Molecular Biology, Temple University Medical School, Philadelphia, PA 19140.
Diabetes. 1993 Aug;42(8):1105-8. doi: 10.2337/diab.42.8.1105.
The adrenocortical steroid, dehydroepiandrosterone, has been shown previously to produce an antidiabetic effect in C57BL/KsJ db/db mice. Preliminary clinical data suggest that this steroid may enhance insulin sensitivity in humans. The therapeutic use of dehydroepiandrosterone may be limited by its androgenic action. In a previous study, high-dose dehydroepiandrosterone therapy to postmenopausal women produced marked elevations in plasma testosterone (9-fold) and dihydrotestosterone (20-fold) levels. We previously developed the synthetic steroid, 16 alpha-fluoro-5-androsten-17-one, which lacks the androgenic action of dehydroepiandrosterone yet has retained other biological activities of the native steroid. In this study, administration of 16 alpha-fluoro-5-androsten-17-one in the diet (0.2 and 0.3%) to male C57BL/KsJ db/db mice markedly reduced plasma glucose levels. In contrast, treatment with dehydroepiandrosterone was effective in reducing plasma glucose levels at the 0.2% dose but had no effect at the 0.3% dose, possibly as a result of the androgenic state induced at the higher dose. Dehydroepiandrosterone treatment also produced a 25-fold elevation in plasma testosterone levels and a significant increase in seminal vesicle weights, whereas treatment with 16 alpha-fluoro-5-androsten-17-one had no apparent effect on the weight of the seminal vesicle glands.
肾上腺皮质类固醇脱氢表雄酮先前已被证明可在C57BL/KsJ db/db小鼠中产生抗糖尿病作用。初步临床数据表明，这种类固醇可能会增强人类的胰岛素敏感性。脱氢表雄酮的治疗用途可能会受到其雄激素作用的限制。在先前的一项研究中，对绝经后女性进行高剂量脱氢表雄酮治疗会使血浆睾酮水平（升高9倍）和双氢睾酮水平（升高20倍）显著升高。我们先前开发了合成类固醇16α-氟-5-雄烯-17-酮，它缺乏脱氢表雄酮的雄激素作用，但保留了天然类固醇的其他生物学活性。在本研究中，给雄性C57BL/KsJ db/db小鼠喂食含16α-氟-5-雄烯-17-酮的饮食（0.2%和0.3%）可显著降低血浆葡萄糖水平。相比之下，脱氢表雄酮在0.2%剂量时能有效降低血浆葡萄糖水平，但在0.3%剂量时则无作用，这可能是由于较高剂量诱导的雄激素状态所致。脱氢表雄酮治疗还使血浆睾酮水平升高了25倍，并使精囊重量显著增加，而用16α-氟-5-雄烯-17-酮治疗对精囊腺重量没有明显影响。
