Plasma growth hormone (GH) response to intravenous GH-releasing factor (GRF) in adult rats: evidence for transient pituitary desensitization after GRF stimulation

Détails

ID Serval
serval:BIB_29D080D0C67C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Plasma growth hormone (GH) response to intravenous GH-releasing factor (GRF) in adult rats: evidence for transient pituitary desensitization after GRF stimulation
Périodique
Endocrinology
Auteur(s)
Arsenijevic  Y., Rivest  R. W., Eshkol  A., Sizonenko  P. C., Aubert  M. L.
ISSN
0013-7227 (Print)
Statut éditorial
Publié
Date de publication
10/1987
Volume
121
Numéro
4
Pages
1487-96
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
The ability of human (h)GRF-(1-29)NH2 to stimulate GH secretion was studied in cannulated adult rats. In order to suppress endogenous GRF secretion and the inhibitory action of hypothalamic somatostatin (SRIF), rats were anesthetized with sodium pentobarbital. Intravenous administration of hGRF-(1-29)NH2 elicited a dose-dependent response of plasma GH, with 250 ng/kg being the smallest effective dose in male rats. In female rats, for each dose tested (250 to 70,000 ng/kg), the GH response represented only about 60% that of male rats. Repeated iv stimulations with hGRF-(1-29)NH2 at short time intervals (45 min) produced transient desensitization of pituitary responsiveness to GRF: a blunted GH response to the second and third stimulations was observed both in male and in female rats and for each dose tested. Similar blunted responses were also obtained with repeated injections of native hGRF-(1-44)NH2. The possibility that these blunted responses could be due to incomplete suppression of hypothalamic SRIF secretion by sodium pentobarbital was excluded by the use of rats that were passively immunized against SRIF; in these rats, it was shown that at least 65% of the inhibition of the GH response after the second GRF stimulation was unrelated to SRIF action. Similar transient desensitization to repeated hGRF-(1-29)NH2 stimulations was also observed in conscious rats that were passively immunized against SRIF. This occurrence of blunted responses was shown to be related to the length of the time interval between GRF stimulations, with longer intervals resulting in less or no desensitization. It appears thus that modulation of pituitary responsiveness to the action of GRF is mediated by at least two independent mechanisms in the rat: in addition to the inhibitory action imposed by hypothalamic SRIF, which induces periods of refractoriness to the action of GRF, it was shown in this study that in the pituitary level each GRF stimulation also induces a transient desensitization of somatotrophs for about 1 h. This period of refractoriness might not be due to excessive stimulation with GRF, since it was also observed with the lowest dose of hGRF-(1-29)NH2 that gave a significant release of GH. Finally, a sex difference was confirmed for the response of anesthetized adult rats to stimulation with hGRF-(1-29)NH2, reflecting a sex steroid-induced modification of pituitary responsiveness to GRF stimulation.
Mots-clé
Anesthesia, General Animals Dose-Response Relationship, Drug Female Growth Hormone/*blood/*pharmacology Growth Hormone-Releasing Hormone/analogs & derivatives/pharmacology Injections, Intravenous Male Peptide Fragments/pharmacology Pituitary Gland/*drug effects Rats Rats, Inbred Strains Sermorelin Somatostatin/pharmacology Stimulation, Chemical Time Factors
Pubmed
Web of science
Création de la notice
28/01/2008 13:31
Dernière modification de la notice
03/03/2018 15:21
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