Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.
The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)- and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of [D-Trp6]LH-RH (50 micrograms/day), early after inoculation of the GH3 tumor, inhibited tumor growth by more than 90% as compared to controls. Similarly, in two experiments, a single once-a-month injection of long-acting [D-Trp6]LH-RH microcapsules (in a dose calculated to release about 25 micrograms/day for 30 days) inhibited the growth of GH3 pituitary tumor by more than 50% 6 or 13 wk after transplantation, when the tumors were fully developed. Serum GH and PRL levels also were reduced markedly by treatment with [D-Trp6]LH-RH. On the other hand, the administration of an antagonistic analog of LH-RH, N-Ac-[D-Phe(4Cl)1,2, D-Trp3, D-Arg6, D-Ala10]LH-RH, did not significantly reduce the growth of this tumor, and the treatment with two different analogs of somatostatin, cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr NH2, appeared to enhance it. These results are in agreement with previous findings of growth inhibition of 7315a pituitary tumors with different hormone-secreting characteristics by agonistic analogs of LH-RH. The collective data from experimental work with rat pituitary tumor models support the contention that the use of [D-Trp6]LH-RH might be considered for the treatment of some patients with pituitary tumors who failed to respond to conventional therapy.
Torres-Aleman
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I
Redding
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TW
Schally
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AV
D000818:Animals; D002214:Capsules; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013006:Growth Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000187:drug effects; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D017329:Triptorelin Pamoate
D002214:Capsules; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D011388:Prolactin; D007986:Luteinizing Hormone; D013006:Growth Hormone