促黄体生成素释放激素和生长抑素类似物治疗后实验性前列腺癌中催乳素、生长抑素和促黄体生成素释放激素的受体

Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin.

作者信息

Kadar T, Redding T W, Ben-David M, Schally A V

机构信息

Endocrine, Polypeptide and Cancer Institute, Tulane University School of Medicine, New Orleans, LA 70146.

出版信息

Proc Natl Acad Sci U S A. 1988 Feb;85(3):890-4. doi: 10.1073/pnas.85.3.890.

DOI:10.1073/pnas.85.3.890

PMID:2893378

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC279662/

Abstract

Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors.

摘要

在用促黄体生成激素释放激素（LH-RH）激动剂[D-色氨酸6]LH-RH和生长抑素类似物RC-160的微胶囊进行体内治疗后，对邓宁R-3327H大鼠前列腺腺癌标本中的LH-RH、生长抑素和催乳素（PRL）膜受体进行了研究。LH-RH受体表现出低结合亲和力（Kd = 54 nM）和高容量（Bmax = 12.0 pmol/mg）。用[D-色氨酸6]LH-RH处理降低了结合亲和力（Kd = 0.52 microM）。还发现了特异性生长抑素受体，其Kd = 1.3 nM，Bmax = 543 fmol/mg。用[D-色氨酸6]LH-RH处理使Bmax降至44 fmol/mg，而给予RC-160使Kd降至30 nM。在用两种类似物联合治疗后，Kd和Bmax均降低。还检测到特异性PRL受体（Kd = 0.72 nM；Bmax = 161 fmol/mg）。用任何一种类似物处理均可使Bmax降低50%，但在用MgCl2体外解离结合的内源性PRL后，PRL结合能力的降低更为显著。在用两种类似物联合治疗后，PRL受体总数的急剧下降可能部分导致了前列腺肿瘤重量和体积的减少。这些发现支持了LH-RH和生长抑素类似物可通过其各自的受体直接抑制肿瘤的概念。这些类似物抗肿瘤活性的几种机制之一可能是通过减少PRL受体总数来消除PRL的促肿瘤生长作用。