Azad N, Uddin S, La Paglia N, Kirsteins L, Emanuele N V, Lawrence A M, Kelley M R
Department of Research, Department of Veterans Affairs, Edward Hines Jr. Hospital, Hines, Illinois 60141.
Endocrinology. 1993 Sep;133(3):1252-7. doi: 10.1210/endo.133.3.8365367.
Continuous administration of LHRH agonist suppresses the pituitary-gonadal axis, achieving chemical castration. Thus, LHRH agonist has been used as an alternative (to surgical castration) for the treatment of steroid-dependent prostate cancer. However, recent reports have demonstrated that LHRH agonist had a direct inhibiting effect on prostate cancer cell proliferation and that cancerous prostate tissue contained a LHRH-like peptide. In this paper we are reporting for the first time that the normal rat ventral prostate contained immunoactive and bioactive LHRH as well as its precursor molecule, pro-LHRH. Our investigation showed that the LHRH concentration in prostate increased 2 weeks after castration from 1.68 +/- 0.09 to 3 +/- 0.2 pg/mg tissue (P < 0.001). At the same time, the concentration of pro-LHRH decreased from 149 +/- 6.5 to 68 +/- 6.8 pg/mg tissue (P < 0.001). Furthermore, intact rat prostate expressed LHRH mRNA, which increased 13-fold 2 weeks after castration. In summary, the prostate of intact Sprague-Dawley rats has the capacity to produce the LHRH precursor and process it to the mature decapeptide, and this production/processing increases significantly after castration.
持续给予促性腺激素释放激素(LHRH)激动剂可抑制垂体 - 性腺轴,实现化学去势。因此,LHRH激动剂已被用作(手术去势的)替代方法来治疗激素依赖性前列腺癌。然而,最近的报告表明,LHRH激动剂对前列腺癌细胞增殖具有直接抑制作用,并且癌性前列腺组织含有一种LHRH样肽。在本文中,我们首次报道正常大鼠腹侧前列腺含有免疫活性和生物活性的LHRH及其前体分子,即LHRH原。我们的研究表明,去势后2周,前列腺中的LHRH浓度从1.68±0.09 pg/mg组织增加到3±0.2 pg/mg组织(P<0.001)。同时,LHRH原的浓度从149±6.5 pg/mg组织降至68±6.8 pg/mg组织(P<0.001)。此外,完整大鼠前列腺表达LHRH mRNA,去势后2周其增加了13倍。总之,完整的斯普拉格 - 道利大鼠的前列腺具有产生LHRH前体并将其加工成成熟十肽的能力,并且这种产生/加工在去势后显著增加。