Ofner P, Douglas W H, Spilman S D, Vena R L, Krinsky-Feibush P, LeQuesne P W
J Steroid Biochem. 1985 Mar;22(3):391-7. doi: 10.1016/0022-4731(85)90443-1.
Hydroxylations of 3 beta-hydroxy 5 alpha-dihydro C19-steroids are terminal reactions by which male accessory sex organs dispose of intracellular androgens. Cellular androgen egress is of particular interest in benign prostatic hyperplasia (BPH) where the elevated nuclear 5 alpha-dihydrotestosterone-receptor content may be implicated in the etiology of the disease. We here report substitution of hydroxyl groups at C-6 alpha, C-7 beta and predominantly at C-7 alpha of [3H]5 alpha-androstane-3 beta,17 beta-diol on incubation of 3 and 8.5 nM substrate concentrations with minced and explanted human BPH tissue. Fibroblasts isolated from the same prostatectomy specimen hydroxylated 3 nM radiosubstrate mainly at C-6 alpha, with extensive metabolism to 17-oxosteroids. Epithelial cells from the same tissue source substituted to the same extent at the three positions. Competing 3 beta-hydroxysteroid dehydrogenase exceeded hydroxylase activity only in epithelial-cell cultures. Our findings support previous evidence that prostatic epithelial and stromal cells make different contributions to androgen disposition by the 3 beta-hydroxysteroid pathway.
3β-羟基-5α-二氢C19类固醇的羟化作用是雄性附属性器官处理细胞内雄激素的终末反应。细胞雄激素流出在良性前列腺增生(BPH)中特别受关注,在该疾病中,细胞核5α-二氢睾酮受体含量升高可能与疾病病因有关。我们在此报告,在3 nM和8.5 nM底物浓度下,将[3H]5α-雄烷-3β,17β-二醇与切碎并移植的人BPH组织一起孵育时,C-6α、C-7β处尤其是C-7α处的羟基被取代。从同一前列腺切除标本中分离出的成纤维细胞主要在C-6α处将3 nM放射性底物羟化,并广泛代谢为17-氧代类固醇。来自同一组织来源的上皮细胞在这三个位置的取代程度相同。只有在上皮细胞培养物中,竞争性3β-羟类固醇脱氢酶才超过羟化酶活性。我们的发现支持了先前的证据,即前列腺上皮细胞和基质细胞对3β-羟类固醇途径的雄激素处理有不同贡献。