Labrie C, Flamand M, Bélanger A, Labrie F
Laboratory of Molecular Endocrinology CHUL Research Center, Québec, Canada.
J Endocrinol. 1996 Sep;150 Suppl:S107-18.
Dehydroepiandrosterone (DHEA) administered percutaneously by twice daily application for 7 days to the dorsal skin of the rat stimulates an increase in ventral prostate weight with approximately one third the potency of the compound given by subcutaneous injection. The doses required to achieve a 50% reversal of the inhibitory effect of orchiectomy are approximately 3 and 1 mg respectively. By the oral route, on the other hand. DHEA has only 10-15% of the activity of the compound given percutaneously. Taking the bioavailability obtained by the subcutaneous route as 100%, it is estimated that the potencies of DHEA by the percutaneous and oral routes are approximately 33 and 3% respectively. Similar ratios of activity were obtained when dorsal prostate and seminal vesicle weight were used as parameters of androgenic activity. When examined on an estrogen-sensitive parameter, namely uterine weight in ovariectomized rats, the stimulatory effect of DHEA was much less potent than its androgenic activity measured in the male animal, a 50% reversal of the inhibitory effect of ovariectomy on uterine weight being observed at the 3 and 30 mg doses of DHEA administered by the subcutaneous and percutaneous routes respectively. When measured on uterine weight, percutaneous DHEA thus shows a 10% potency compared with the subcutaneous route. The sulfate of DHEA (DHEA-S), on the other hand, was approximately 50% as potent as DHEA at increasing ventral prostate weight after subcutaneous or percutaneous administration. When the effect was measured on dorsal prostate and seminal vesicle weight, percutaneous DHEA-S had 10-25% of the activity of DHEA. DHEA decreased serum LH levels in ovariectomized animals, an effect which was completely reversed by treatment with the antiandrogen flutamide. On the other hand, flutamide had no significant effect on the increase in uterine weight caused by DHEA, thus suggesting a predominant estrogenic effect of DHEA at the level of the uterus and an estrogenic effect on the feedback control of LH secretion. The present data show a relatively high bioavailability of percutaneous DHEA as measured by its androgenic and/or estrogenic biological activity in well-characterized peripheral target intracrime tissues in the rat.
将脱氢表雄酮（DHEA）每日两次经皮给药于大鼠背部皮肤，持续7天，可刺激腹侧前列腺重量增加，其效力约为皮下注射该化合物的三分之一。实现去势抑制作用50%逆转所需的剂量分别约为3毫克和1毫克。另一方面，经口服途径，DHEA的活性仅为经皮给药化合物的10 - 15%。以皮下途径获得的生物利用度为100%计算，估计经皮和口服途径的DHEA效力分别约为33%和3%。当以背侧前列腺和精囊重量作为雄激素活性参数时，也获得了类似的活性比率。当在雌激素敏感参数（即去卵巢大鼠的子宫重量）上进行检测时，DHEA的刺激作用远不如在雄性动物中测量的雄激素活性强，皮下和经皮途径分别给予3毫克和30毫克剂量的DHEA时，观察到去卵巢对子宫重量的抑制作用有50%的逆转。以子宫重量衡量，经皮DHEA与皮下途径相比，效力仅为10%。另一方面，DHEA的硫酸盐（DHEA - S）在皮下或经皮给药后增加腹侧前列腺重量方面的效力约为DHEA的50%。当以背侧前列腺和精囊重量衡量效果时，经皮DHEA - S的活性为DHEA的10 - 25%。DHEA降低了去卵巢动物的血清促黄体生成素（LH）水平，抗雄激素氟他胺治疗可完全逆转这一作用。另一方面，氟他胺对DHEA引起的子宫重量增加无显著影响，因此表明DHEA在子宫水平具有主要的雌激素作用，且对LH分泌的反馈控制具有雌激素作用。目前的数据表明，通过在大鼠特征明确的外周靶组织中测量其雄激素和/或雌激素生物活性，经皮DHEA具有相对较高的生物利用度。
