Effects of combined long-term treatment with a growth hormone-releasing hormone analogue and a growth hormone secretagogue in the growth hormone-releasing hormone knock out mouse.
GH secretagogues (GHS) are synthetic ghrelin receptor agonists that stimulate GH secretion. It is not clear whether they act predominantly by stimulating the secretion of hypothalamic growth hormone-releasing hormone (GHRH), or directly on the somatotrope cells. In addition, it is not known whether combined treatment with GHRH and GHS has synergistic effects on growth. To address these questions, we used the GH-deficient GHRH knock out (GHRHKO) mouse model, which has severe somatotrope cell hypoplasia. We treated GHRHKO mice for 5 weeks (from week 1 to week 6 of age) with the GHRH analogue JI-38 alone, or in combination with a GHS (GHRP-2), and at the end of the treatment we examined their response to an acute stimulus with GHRP-2 or GHRP-2 plus JI-38. We used placebo-treated GHRHKO mice and animals heterozygous for the GHRHKO allele as controls. Animals treated with JI-38+GHRP-2 reached higher body length and weight than animals treated with JI-38 alone. All the animals receiving JI-38 (with or without GHRP-2) showed similar correction of somatotrope cell hypoplasia. None of the GHRHKO animals showed a serum GH response to the acute stimulation with GHRP-2 alone, while both treated groups responded to the combined test with JI-38 + GHRP-2. These data demonstrate that in GHRHKO mice, GHRP-2 has a growth-stimulating effect that augments the response induced by JI-38. In addition, the presence of GHRH seems necessary for the stimulation of GH secretion by GHRP-2.
Fintini
Danilo
D
Department of Medicine, Division of Endocrinology, and the Ilyssa Center for Molecular and Cellular Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alba
Maria
M
Schally
Andrew V
AV
Bowers
Cyril Y
CY
Parlow
A F
AF
Salvatori
Roberto
R
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors
C420262:JI-38; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone