Role of selected endogenous peptides in growth hormone-releasing hexapeptide activity: analysis of growth hormone-releasing hormone, thyroid hormone-releasing hormone, and gonadotropin-releasing hormone.
The purpose of this study was to evaluate the contribution of endogenous GH-releasing hormone (GHRH) to exogenous GH-releasing hexapeptide (GHRP-6) activity, and to determine whether TRH or GnRH are endogenous analogs of GHRP-6. The activity of GHRP-6, a synthetic GH secretagogue, was significantly attenuated in rats administered GHRH antiserum or alpha-methyl-rho-tyrosine to reduce endogenous GHRH concentrations, and also in rats administered 5-50 micrograms/kg of [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide to block pituitary GHRH receptors. However, GHRP-6 activity was potentiated in rats administered 150 micrograms/kg [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide, presumably due to partial agonist activity of the GHRH receptor antagonist at the higher dose. These data show that endogenous GHRH contributes to full expression of exogenous GHRP-6 activity in vivo. Like TRH, a subthreshold dose of GHRP-6 was significantly more effective in hypothyroid rats than in euthyroid rats. However, suprathreshold doses of GHRP-6 were less effective in hypothyroid rats. Unlike TRH, GHRP-6 had no effect on GH and prolactin release from GH3 cells, and TRH and GnRH were poor competitors for 3H-GHRP-6 binding sites on pituitary membranes. A GnRH receptor antagonist did not block GHRP-6 activity in vivo, and GnRH administered alone or in combination with GHRP-6, did not stimulate GH release. The results of this study suggest that synergy between GHRH and GHRP-6 seen in pharmacological studies is physiologically relevant, and that TRH and GnRH are not endogenous analogs of GHRP-6.
Bercu
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BB
Department of Pediatrics, University of South Florida, Tampa 33612.
Yang
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Masuda
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Walker
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RF
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D006728:Hormones / Q000494:pharmacology; D007037:Hypothyroidism / Q000503:physiopathology; D007106:Immune Sera; D008713:Methimazole / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010911:Pituitary Neoplasms; D051381:Rats; D011919:Rats, Inbred Strains; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013961:Thyroid Gland / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D019805:alpha-Methyltyrosine
D006728:Hormones; D007106:Immune Sera; D008781:Methyltyrosines; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C054880:growth hormone releasing hexapeptide, Lys(6), thionated; D014284:Triiodothyronine; D008713:Methimazole; D019805:alpha-Methyltyrosine; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor; D013974:Thyroxine