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

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-TrpWLH-RH (Kd = 0.72 nM; B, = 161 fmol/mg) were also detected. Treatment with either analog reduced Bx by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgC12. 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.The primary treatment of advanced prostate carcinomas is based on the elimination of testicular androgen secretion by hormonal manipulation (1-3). A new endocrine therapy for prostate cancer makes use of superactive agonists of luteinizing hormone-releasing hormone (LH-RH) that after chronic administration produces an inhibition of circulating testosterone (2-5). The development of once-a-month injectable microcapsules of an analog of LH-RH with Dtryptophan in position 6 ([D-Trp6]LH-RH), in a biodegradable polymer, provides'a practical, convenient, and efficacious way of administration (3-6).Other hormones in addition to testosterone could influence the growth of prostatic carcinoma. Prolactin (PRL) could be involved in prostate cancer as a cofactor (4, 5). It was demonstrated that 'PRL potentiates the effects of testosterone on the prostate (7,8), and PRL receptors are found in normal and cancerous prostate tissue (9,10 890The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Regulation of luteinizing hormone-releasing hormone receptor binding by heterologous and autologous receptor-stimulated tyrosine phosphorylation.

“…The higher binding is consistent with the fact that in our work pure pancreatic cancer cell membranes were used from a cell culture line known to be responsive to EGF (10). In addition, the affinity constant was somewhat lower (i.e., binding was of higher affinity) but of a similar order as previously reported (33,34). This supports the view that the LH-RHRs investigated by us are similar to LH-RHRs reported by others.…”

“…The results of pretreatment with EGF are shown in Fig. 2A (33,34). The higher binding is consistent with the fact that in our work pure pancreatic cancer cell membranes were used from a cell culture line known to be responsive to EGF (10).…”

Neuroendocrine cells in tumour growth of the prostate.

“…These analogues also affect prostatic carcinoma in a complex manner, with their effects possibly being mediated by the inhibitory action of somatostatin on the release of pituitary growth hormone and prolactin or, more locally, through interference with endogenous growth factors such as EGF (Schally & Redding 1987, Kadar et al 1988, Pinski et al 1993. Somatostatin receptors have been found in rat prostatic cancer cell lines (Kadar 1988, Pinski et al 1993, which suggests that somatostatin has a direct effect. Indeed, the somatostatin analogue, RC-160, was found to inhibit the growth of the androgen-independent rat prostatic cancer cell line, Dunning R-3327-AT-1 (Pinski et al 1994), and xenografts of the human prostate cancer cell line DU-145 in nude mice (Pinski et al 1993).…”

“…There is also evidence that, under certain circumstances, somatostatin analogues inhibit neuroendocrine tumour growth, resulting in a decrease in tumour size (Reubi 1985, Kvols et al 1986, Pinski et al 1993. These analogues also affect prostatic carcinoma in a complex manner, with their effects possibly being mediated by the inhibitory action of somatostatin on the release of pituitary growth hormone and prolactin or, more locally, through interference with endogenous growth factors such as EGF (Schally & Redding 1987, Kadar et al 1988, Pinski et al 1993. Somatostatin receptors have been found in rat prostatic cancer cell lines (Kadar 1988, Pinski et al 1993, which suggests that somatostatin has a direct effect.…”

The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors

“…There have also been reports of the presence of GnRH-binding sites in breast cancer cells (Eidne et al, 1987), pancreatic tumours (Szende et al, 1989) and induced rat prostatic cancers (Kadar et al, 1988). The binding of GnRH to breast cancer cells has been shown to result in growth modulation (Millar et al, 1985;Eidne et al, 1987).…”