Marchetti B, Poulin R, Plante M, Labrie F
MRC Group in Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Quebec, Canada.
J Steroid Biochem. 1988 Oct;31(4A):411-9. doi: 10.1016/0022-4731(88)90309-3.
In order to assess the biological significance of low serum androgens comparable to those which remain after castration in men treated for prostate cancer. Silastic depots continuously releasing predetermined doses of testosterone (T) have been implanted into castrated adult male rats in the absence or presence of simultaneous treatment with the pure antiandrogen Flutamide. Quite remarkably, a 3- to 5-fold increase in prostate weight (P less than or equal to 0.001) was observed at plasma T concentrations comparable to those found in the serum of castrated men. Although of lower magnitude, castration levels of plasma T also caused a significant stimulation of seminal vesicle weight (P less than 0.01). This dramatic stimulatory influence of "castration" levels of plasma T on ventral prostate and seminal vesicle weight can be explained by the 13- to 15-fold higher intraprostatic level of the active androgen dihydrotestosterone (DHT) compared to the plasma T concentration. In fact, a near-maximal intraprostatic concentration of DHT is reached at concentrations of plasma T of 0.2-0.5 ng/ml and a positive correlation was found between prostatic DHT concentration and ventral prostate weight. Prostatic growth and DHT concentrations were also positively correlated with ornithine decarboxylase (ODC) activity, an enzyme highly sensitive to androgens in the rat ventral prostate. In fact, a dramatic (30-fold) increase in ODC activity was observed at plasma T values corresponding to those found in castrated men. The level of prostatic beta 2-adrenergic receptors fell within 10 days of castration and an increase in beta 2-adrenergic receptor concentration was observed with low doses of T, thus indicating that beta 2-adrenoreceptor levels are also a sensitive parameter of androgenic activity in the rat prostate.(ABSTRACT TRUNCATED AT 250 WORDS)
为了评估低血清雄激素的生物学意义，这些雄激素水平与接受前列腺癌治疗的男性去势后残留的雄激素水平相当。在成年去势雄性大鼠体内植入持续释放预定剂量睾酮（T）的硅橡胶储库，同时或不同时给予纯抗雄激素氟他胺治疗。值得注意的是，当血浆T浓度与去势男性血清中的浓度相当时，前列腺重量增加了3至5倍（P≤0.001）。虽然程度较低，但血浆T的去势水平也显著刺激了精囊重量（P＜0.01）。血浆T的“去势”水平对腹侧前列腺和精囊重量的这种显著刺激作用，可以通过前列腺内活性雄激素双氢睾酮（DHT）的水平比血浆T浓度高13至15倍来解释。事实上，当血浆T浓度为0.2 - 0.5 ng/ml时，前列腺内DHT浓度接近最大值，并且发现前列腺DHT浓度与腹侧前列腺重量之间存在正相关。前列腺生长和DHT浓度也与鸟氨酸脱羧酶（ODC）活性呈正相关，ODC是一种对大鼠腹侧前列腺中的雄激素高度敏感的酶。实际上，在与去势男性血浆T值相当的情况下，观察到ODC活性急剧（30倍）增加。前列腺β2 - 肾上腺素能受体水平在去势后10天内下降，低剂量T可使β2 - 肾上腺素能受体浓度增加，因此表明β2 - 肾上腺素能受体水平也是大鼠前列腺雄激素活性的一个敏感参数。（摘要截断于250字）
