Guthrie P D, Freeman M R, Liao S T, Chung L W
Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Mol Endocrinol. 1990 Sep;4(9):1343-53. doi: 10.1210/mend-4-9-1343.
Denervation of rat ventral prostate has been accomplished by excising prostatic tissue fragments and implanting them under the renal capsules of intact syngeneic rats. This resulted in a substantial reduction of expression of a major organ-specific secretory protein, prostatic binding protein (PBP). The depressed level of PBP and its subunits and mRNAs could be restored, however, to as much as 80% of control levels by the administration of a pharmacological dose of exogenous androgen, testosterone propionate (TP), and/or a beta-adrenergic agonist, isoproterenol (ISO). Furthermore, compared to ascorbate-treated controls, TP and ISO increased the synthesis of total cellular protein and PBP by the prostatic renal implants. TP and/or ISO also remodelled the luminal epithelial structure and elevated secretory functions. ISO alone had no effect, however, in castrated animals, indicating that androgen plays a dominant role in the restoration of tissue PBP content. Concomitant to increased PBP content and remodelling of prostatic histomorphology, androgen was also found to raise the depressed levels of beta 2-adrenergic and androgen receptors in the prostatic isografts maintained in intact hosts. In contrast, although an established rat prostatic epithelial cell line (NbE-1) contains high affinity androgen receptor, androgen failed to restore beta-adrenergic receptor as well as PBP content in this cultured cell line. These results, taken together, suggest that a tight coupling between androgen receptor and beta 2-adrenergic receptor pathways may be a prerequisite for PBP expression and functional differentiation in the rat ventral prostate gland.
通过切除大鼠腹侧前列腺组织碎片并将其植入同基因完整大鼠的肾被膜下，实现了大鼠腹侧前列腺的去神经支配。这导致一种主要的器官特异性分泌蛋白——前列腺结合蛋白（PBP）的表达大幅降低。然而，通过给予药理剂量的外源性雄激素丙酸睾酮（TP）和/或β-肾上腺素能激动剂异丙肾上腺素（ISO），PBP及其亚基和mRNA的降低水平可恢复至对照水平的80%。此外，与用抗坏血酸处理的对照组相比，TP和ISO增加了前列腺肾植入物中总细胞蛋白和PBP的合成。TP和/或ISO还重塑了管腔上皮结构并提高了分泌功能。然而，单独使用ISO对去势动物没有影响，这表明雄激素在组织PBP含量的恢复中起主导作用。与PBP含量增加和前列腺组织形态重塑相伴的是，还发现雄激素可提高完整宿主中前列腺同基因移植体中β2-肾上腺素能受体和雄激素受体的降低水平。相比之下，尽管已建立的大鼠前列腺上皮细胞系（NbE-1）含有高亲和力雄激素受体，但雄激素未能恢复该培养细胞系中的β-肾上腺素能受体以及PBP含量。综合这些结果表明，雄激素受体和β2-肾上腺素能受体途径之间的紧密耦合可能是大鼠腹侧前列腺中PBP表达和功能分化的先决条件。
