Decrease in prolactin receptor affinity in the rat mammary tumor model after treatment with analogs of somatostatin and LH-RH
Kadar, T.; Redding, T.W.; Ben-David, M.; Schally, A.V.
Materia Medica Polona. Polish Journal of Medicine and Pharmacy 20(4): 219-223
1988
ISSN/ISBN: 0025-5246 PMID: 2907923 Document Number: 313557
Female rats bearing the MT/W9A mammary adenocarcinoma were treated with the somatostatin analog RC-160, subcutaneously or in a delayed delivery formulation, and with microcapsules of the agonist D-Trp-6-LH-RH. Administration of these peptides alone or in combination inhibited tumor growth. After 21 days of treatment, the characteristics of prolactin (PRL) receptor binding were determined in tumor membranes. The control group showed significant amounts of PRL receptors with high affinity (Kd = 5.3 .times. 10-11 M) and low capacity (Bmax = 29 fmol/mg protein). Administration of both analogs resulted in a decrease in the affinity of PRL binding and some increase in binding capacities. The greatest effects on receptors were observed in the groups treated with RC-160 microcapsules (Kd = 6.9 .times. 10-10; Bmax = 103 fmol/mg protein) and with the combination of microcapsules of both peptides (analogs) (Kd = 6.1 .times. 10-10; Bmax = 70 fmol/mg protein). In vitro desaturation of the membranes form bound endogenous PRL with 3 M MgCl2 did not increase the number of PRL receptors in any group, which indicates that most receptors were free of the endogenous hormone. Our data indicate the treatment with analogs of somatostatin and LH-RH decreases the affinity of PRL receptors in the experimental mammary tumor model. This effect may be involved in the mechanism of inhibition by the analogs of the mammary tumor growth.