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Inhibition of prostate tumors by agonistic and antagonistic analogs of LH‐RH
Author(s) -
Schally Andrew V.,
Redding Tommie W.,
ComaruSchally Ana Maria
Publication year - 1983
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.2990040602
Subject(s) - endocrinology , medicine , prostate , antagonist , prolactin , agonist , testosterone (patch) , hormone , receptor , cancer
We have compared the effects of chronic administration of D‐Trp 6 ‐LH‐RH, a superactive agonist of LH‐RH, and a potent antagonist, (NAc‐p‐CI‐D‐Phe 1,2 , D‐Trp 3 , D‐Arg 6 , D‐Ala 10 )LH‐RH, on male Copenhagen F‐1 rats bearing the Dunning R‐3327H prostate adenocarcinoma. Treatment with 25 μg of D‐Trp 6 ‐LH‐RH bid for 21 days decreased the weights of the ventral prostate, testes, and adrenals, but had no effect on the weight of the anterior pituitary gland. Administration of similar doses of the antagonist reduced the weight of the ventral prostate, anterior pituitary gland, and adrenals, but did not change the weight of the testes. Both the agonist and antagonist greatly and significantly reduced tumor weight and volume as compared to controls. Serum LH, prolactin, and testosterone levels in Copenhagen F‐1 rats bearing Dunning tumors were significantly decreased after treatment with D‐Trp 6 ‐LH‐RH as well as the antagonist. The inhibition of rat prostate tumors achieved with D‐Trp 6 ‐LH‐RH and the antagonistic analog raised the possibility that these compounds could be used clinically in the treatment of prostate carcinoma and other endocrine‐dependent neoplasias. The antagonistic analogs have not yet been tried clinically on a chronic basis. However, the data accumulated so far from clinical trials in men with prostate carcinoma suggest that D‐Trp 6 ‐LH‐RH and other LH‐RH agonists can be used for an effective therapy which avoids the side effects of estrogen and the pyschological impact of castration.