Circannual variation in the human serum levels of prostate-specific antigen, a growth marker of the prostate gland, has been reported recently. The present study was conducted to investigate the role of the photoperiodic hormone melatonin (MLT) and its membrane receptors in the modulation of human prostate growth. Expression of MT(1) and MT(2) receptors was detected in benign human prostatic epithelial tissues and RWPE-1 cells. MLT and 2-iodomelatonin inhibited RWPE-1 cell proliferation and up-regulated p27(Kip1) gene and protein expression in the cells. The effects of MLT were blocked by the nonselective MT(1)/MT(2) receptor antagonist luzindole, but were not affected by the selective MT(2) receptor antagonist 4-phenyl-2-propionamidotetraline. Of note, the antiproliferative action of MLT on benign prostate epithelial RWPE-1 cells was effected via increased p27(Kip1) gene transcription through MT(1) receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel, a signaling process which has previously been demonstrated in 22Rv1 prostate cancer cells. Taken together, the demonstration of the MT(1)/PKA+PKC/p27(Kip1) antiproliferative pathway in benign and malignant prostate epithelial cell lines indicated the potential importance of this MLT receptor-mediated signaling mechanism in growth regulation of the human prostate gland in health and disease. Collectively, our data support the hypothesis that MLT may function as a negative mitogenic hormonal regulator of human prostate epithelial cell growth.

中文翻译：

---

褪黑激素作为人类前列腺上皮细胞生长的有丝分裂激素的负调节剂：潜在的机制和临床意义。

最近已经报道了人类血清中前列腺特异性抗原（一种前列腺的生长标志物）的水平变化。进行本研究以研究光周期激素褪黑激素（MLT）及其膜受体在调节人类前列腺生长中的作用。在良性人类前列腺上皮组织和RWPE-1细胞中检测到MT（1）和MT（2）受体的表达。MLT和2-iodomelatonin抑制RWPE-1细胞增殖并上调p27（Kip1）基因和蛋白质表达。MLT的作用被非选择性MT（1）/ MT（2）受体拮抗剂luzindole阻断，但不受选择性MT（2）受体拮抗剂4-phenyl-2-propionamidotetraline影响。值得注意的是 MLT对良性前列腺上皮RWPE-1细胞的抗增殖作用是通过同时通过MT（1）受体介导的蛋白激酶A（PKA）和蛋白激酶C（PKC）激活增加的p27（Kip1）基因转录来实现的，之前已在22Rv1前列腺癌细胞中证实的信号转导过程。综上所述，在良性和恶性前列腺上皮细胞系中MT（1）/ PKA + PKC / p27（Kip1）抗增殖途径的演示表明，这种MLT受体介导的信号传导机制在人类前列腺生长调节中具有潜在的重要性。在健康和疾病方面。总体而言，我们的数据支持以下假设：MLT可能充当人类前列腺上皮细胞生长的有丝分裂激素负调节剂。