Receptors for luteinizing hormone‐releasing hormone, somatostatin, prolactin, and epidermal growth factor in rat and human prostate cancers and in benign prostate hyperplasia

Matyas Fekete, Tommie W. Redding, Ana Maria Comaru‐Schally, J. Edson Pontes, Robert W. Connelly, Gordan Srkalovic, Andrew V. Schally

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Using sensitive multipoint micromethods, we estimated membrane receptors for [D-Trp6]-luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH), somatostatin (SS-14), human prolactin (hPRL), and epidermal growth factor (EGF) in experimental Dunning rat prostate cancers and in samples of normal human prostate, benign prostatic hyperplasia (BPH), and human prostate cancer (PC) obtained from biopsy, aftere prostatectomy, or at autopsy. In the Dunning R-3327 rat prostate adenocarcinoma specimens, the receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist [D-Trp6]-LH-RH and the somatostatin analog RC-160. Two populations of binding sites were found for [D-Trp6]-LH-RH, one with high affinity and low capacity and another with low affinity and high capacity. Treatment with [D-Trp6]-LH-RH and RC-160 alone or with the combination of these analogs increased the binding capacity (B(max)) of the low-affinity binding sites for [D-Trp6]-LH-RH and decreased B(max) for hPRL and EGF. Therapy with [D-Trp6]-LH-RH also reduced B(max) of SS-14 binding and dissociation binding constant of high-affinity binding sites for [D-Trp6]-LH-RH, whereas administration of RC-160 or the combination treatment with both analogs increased B(max) of SS-14 binding. These findings are compatible with the view that analogs of LH-RH and SS-14 might exert some direct inhibitory effects on the Dunning prostate cancer. Among 13 human BPH samples examined, only one had receptors for [D-Trp6]-LH-RH, and seven specimens exhibited binding for prolactin. [D-Trp6]-LH-RH receptors were found in all seven samples of human PC but not in any of the eight specimens of normal human prostate. All samples of normal human prostate, BPH, and human PC exhibited binding sites for EGF but not for SS-14. Our findings on the membrane receptors in the human and rat prostate cancers raise the intriguing possibility that LH-RH, acting as a growth factor, along with EGF and prolactin, might be involved in complex interactions that contribute to the promotion of prostate cancer in man.

Original languageEnglish (US)
Pages (from-to)191-208
Number of pages18
JournalThe Prostate
Volume14
Issue number3
DOIs
StatePublished - 1989
Externally publishedYes

Keywords

  • BPH
  • EGF
  • peptide receptors for LH‐RG
  • prolactin
  • prostate carcinoma
  • somatostatin

ASJC Scopus subject areas

  • Oncology
  • Urology

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