Labrie C, Belanger A, Labrie F
Medical Research Council Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
Endocrinology. 1988 Sep;123(3):1412-7. doi: 10.1210/endo-123-3-1412.
In order to assess the androgenic potency of physiological plasma concentrations of the adrenal steroids dehydroepiandrosterone (DHEA) and androstenedione (delta 4-dione) in the rat prostate, these two steroids were released from Silastic tubings of appropriate length and size in castrated male rats. Implants of DHEA led to plasma levels of DHEA and 5-androsten-3 beta,17 beta-diol covering the range of concentrations found in adult men while no significant change was observed in plasma levels of delta 4-dione, testosterone and dihydrotestosterone (DHT). delta 4-Dione implants, on the other hand, led to a parallel increase in plasma delta 4-dione and testosterone levels at all doses used while plasma DHT only increased at supraphysiological doses of delta 4-dione. At plasma concentrations comparable to those found in adult men; delta 4-dione (0.8 ng/ml) and DHEA (3.4 ng/ml) stimulated prostate weight 3.7- and 2.1-fold, respectively. In the same groups, prostatic DHT levels were elevated at 4.48 +/- 0.05 and 2.70 +/- 0.73 ng/g tissue, respectively. A close parallelism was observed between prostatic DHT levels and prostatic weight in all groups. The present data show that in the rat, a species having no significant secretion of adrenal androgens, plasma concentrations of DHEA and delta 4-dione maintained within the range of those found in adult men are efficiently converted into DHT and act as potent androgenic stimuli in prostatic tissue. The castrated rat bearing Silastic implants releasing constant and predetermined amounts of adrenal steroids offers a good model to study the recently identified role of adrenal steroids in peripheral tissues.
为了评估肾上腺类固醇脱氢表雄酮(DHEA)和雄烯二酮(δ4-二酮)的生理血浆浓度在大鼠前列腺中的雄激素效力,将这两种类固醇从合适长度和尺寸的硅橡胶管中释放到去势雄性大鼠体内。植入DHEA导致血浆中DHEA和5-雄烯-3β,17β-二醇的水平涵盖成年男性体内发现的浓度范围,而δ4-二酮、睾酮和双氢睾酮(DHT)的血浆水平未观察到显著变化。另一方面,植入δ4-二酮导致在所使用的所有剂量下血浆δ4-二酮和睾酮水平平行升高,而血浆DHT仅在超生理剂量的δ4-二酮下升高。在与成年男性体内发现的浓度相当的血浆浓度下,δ4-二酮(0.8 ng/ml)和DHEA(3.4 ng/ml)分别刺激前列腺重量增加3.7倍和2.1倍。在同一组中,前列腺组织中DHT水平分别升高至4.48±0.05和2.70±0.73 ng/g组织。在所有组中,前列腺DHT水平与前列腺重量之间观察到密切的平行关系。目前的数据表明,在大鼠这种肾上腺雄激素分泌不显著的物种中,维持在成年男性体内发现的浓度范围内的DHEA和δ4-二酮血浆浓度可有效转化为DHT,并在前列腺组织中作为强效雄激素刺激物起作用。携带释放恒定和预定剂量肾上腺类固醇的硅橡胶植入物的去势大鼠为研究肾上腺类固醇在周围组织中最近确定的作用提供了一个良好的模型。