help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Horvath, J. E.
Right arrow Articles by Schally, A. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Horvath, J. E.
Right arrow Articles by Schally, A. V.

Endocrinology, Vol 136, 3849-3855, Copyright © 1995 by Endocrine Society

ARTICLES

Effect of long-acting antagonists of growth hormone (GH)-releasing hormone on GH and cyclic adenosine 3',5'-monophosphate release in superfused rat pituitary cells

JE Horvath, M Zarandi, K Groot and AV Schally
Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70146, USA.

In a recent study, investigating the time course of both GH and cAMP secretion induced by GH-releasing hormone (GHRH) in the superfusion system, we found that the amount of cAMP liberated from the cells was not proportional to GH release and that cAMP discharged after a GHRH pulse alone cannot maintain the release of GH. In the present study, two potent antagonists of GHRH, MZ-4-71 ([Ibu0,D-Arg2,Phe(4- Cl)6,Abu15,Nle27]human GHRH-(1-28)Agm) and MZ-4-243 ([Nac0,D-Arg2,Phe(4- Cl)6,Abu15,Nle27]human GHRH-(1-28)Agm) were evaluated for their long term effect in the superfusion system and for their ability to influence the release of GH and cAMP. Our present findings showed that after a 9-min preincubation, antagonist MZ-4-71 and MZ-4-243 at 3 and 1 nM, respectively, caused an inhibition of GH release, stimulated by 1 nM GHRH, similar to that caused by the 100-nM dose of the standard antagonist ([Ac-Tyr1,D-Arg2]human GHRH-(1-29)NH2). The standard antagonist at 100 nM did not influence the GHRH-induced GH response 30 min later, and the inhibition caused by MZ-4-71 at 30 nM decreased gradually to 30% 120 min after the treatment, but the 30-nM dose of MZ- 4-243 reduced the GH response by more than 90% even 270 min after its administration. During a 2-h incubation with 1 nM GHRH in combination with a 30-min infusion of the standard antagonist, MZ-4-71, MZ-4-243, or somatostatin, from the 30th to the 60th min, the decrease in GH discharge preceded the inhibition of cAMP release. After infusion of the antagonists or somatostatin was stopped, GH release resumed sooner than that of cAMP. Simultaneous determinations of cAMP and GH in the samples showed that changes in GH levels were never preceded by a rise or decrease in cAMP release, in contrast to existing information. The participation of more than one signal transduction mechanism in the mediation of the effect of GHRH is very likely, and the balance of these mechanisms may vary with the dose and duration of stimulation.




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1995 by The Endocrine Society