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

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

Research output: Contribution to journalArticle

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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 (K(d) = 54 nM) and high capacity (B(max) = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (K(d) = 0.52 μM). Specific somatostatin receptors, with K(d) = 1.3 nM and B(max) = 543 pmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered B(max) to 44 fmol/mg, and administration of RC-160 reduced K(d) to 30 nM. After the combined treatment with the two analogs, K(d) and B(max) were decreased. Specific PRL receptors (K(d) = 0.72 nM; B(max) = 161 fmol/mg) were also detected. Treatment with either analog reduced B(max) 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.

Original languageEnglish (US)
Pages (from-to)890-894
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number3
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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