In vivo and in vitro Effects of Ghrelin/Motilin-Related Peptide on Growth Hormone Secretion in the Rat
| Autor: | Jacques Epelbaum, Marie-Christine Rio, Marie-Thérèse Bluet-Pajot, Catherine Tomasetto, Philippe Zizzari, Virginie Tolle |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Leptin
Male medicine.medical_specialty Peptide Hormones Endocrinology Diabetes and Metabolism Molecular Sequence Data Growth hormone receptor In Vitro Techniques Motilin Rats Sprague-Dawley Cellular and Molecular Neuroscience Endocrinology Adrenocorticotropic Hormone Growth hormone secretagogue Internal medicine medicine Animals Amino Acid Sequence Receptor Cells Cultured Dose-Response Relationship Drug Endocrine and Autonomic Systems Chemistry digestive oral and skin physiology Ghrelin Peptide Fragments Growth hormone secretion Prolactin Rats Somatostatin Hormone receptor Growth Hormone Pituitary Gland Peptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | Neuroendocrinology. 73:54-61 |
| ISSN: | 1423-0194 0028-3835 |
| Popis: | Ghrelin (Ghr), a 28 amino acid gastric peptide with an n-octanoylation on Ser 3, has recently been identified as an endogenous ligand of the growth hormone secretagogue (GHS) receptor. A cDNA was also isolated from a mouse stomach library encoding a protein named prepromotilin-related peptide (ppMTLRP) which shares sequence similarities with prepromotilin. Mouse and rat ppMTLRP sequences (rGhr) are identical and show 89% identity with human ghrelin (hGhr). By analogy with promotilin, cleavage of proMTLRP into an 18 amino acid endogenous processed peptide can be assumed on the basis of a conserved dibasic motif in position 9–10 of its sequence. In the present work, we compared the GH-releasing activity of rGhr28/MTLRP and of hGhr28/MTRLP with that of a shorter form of the peptide, hGhr18. A short peptide devoid of Ser-3 n-octanoylation hGhr18[–] was also tested. Addition of rGhr28, hGhr28 and hGhr18 stimulated GH release to the same extent from superfused pituitaries. The effect was dose dependent in a 10–8 to 10–6M concentration range. In contrast, hGhr 18[–] was inactive. In freely moving animals, both rGhr28 and hGhr28 (10 µg, i.v.) stimulated GH release, whereas the same dose of hGhr18 or of hGhr18[–] was ineffective. After rGhr28, GH plasma levels increased as early as 5 min after injection and returned to basal values within 40–60 min. Expressed as percent stimulation, administration of rGhr28 was equally effective when injected during troughs or peaks of GH. Plasma concentrations of prolactin, adrenocorticotropin and leptin were not modified. Spontaneous GH secretory episodes were no longer observed within 3 h of rGhr28 treatment, but repeated administration of the secretagogue at 3- to 4-hour intervals resulted in a similar GH response. Activation of somatostatin (SRIH) release by ether stress did not blunt the GH response to rGhr28. This suggests that the secretagogue acts in part by inhibiting endogenous SRIH, as further substantiated by the ability of rGhr28 (10–6M), to decrease the amplitude of 25 mM K+-induced SRIH release from perifused hypothalami. In conclusion, (1) n-octanoylation of Ghrs and the shorter form hGhr18 is essential for the direct pituitary GH-releasing effect of this new family of endogenous GHSs; (2) only the longer forms are active in vivo and (3) inhibition of SRIH release appears involved in the mechanism of Ghr action. |
| Databáze: | OpenAIRE |
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