Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin.
Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin.
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用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、生长抑素和黄体生成素释放激素的受体。
DOI：
10.1073/pnas.85.3.890
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发表时间：
1988
影响因子：
11.1
通讯作者：
Schally,AV
中科院分区：
文献类型：
--
作者：
Kadar,T;Redding,TW;Ben-David,M;Schally,AV
用激动剂[D-Trp6]LH-RH和生长抑素类似物RC-160微胶囊在体内处理后，研究了促黄体生成素释放激素（LH-RH）、生长抑素和催乳素（PRL）的膜受体在Dunning R-3327H大鼠前列腺癌标本中的变化。LH-RH受体具有低结合亲和力（Kd = 54 nM）和高容量（Bmax = 12.0 pmol/mg）。用[D-Trp6]LH-RH处理降低了结合亲和力（Kd = 0.52微米）。特异性生长抑素受体Kd = 1.3 nM, Bmax = 543 fmol/mg。[D-Trp6]LH-RH处理将Bmax降低至44 fmol/mg， RC-160处理将Kd降低至30 nM。两种类似物联合处理后，Kd和Bmax均降低。同时检测到特异性PRL受体（Kd = 0.72 nM, Bmax = 161 fmol/mg）。两种类似物均可使Bmax降低50%，但在MgCl2体外解离结合的内源性PRL后，PRL结合能力的降低幅度更大。两种类似物联合治疗后，PRL受体总数的急剧下降可能是前列腺肿瘤重量和体积减少的部分原因。这些发现支持了rh - rh和生长抑素的类似物可以直接通过它们各自的受体抑制肿瘤的概念。这些类似物的抗肿瘤活性的几种机制之一可能是通过减少PRL受体的总数来消除PRL的促肿瘤生长作用。
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.