Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: I. A study on ad libitum fed and starved adult male rats.
The individual role played by GH and IGF-I in the regulation of hypothalamic GHRH and SRIF gene expression is still object of debate. We have investigated the effect of exogenously administered recombinant hGH (rhGH) and recombinant hIGF-I (rhIGF-I) in ad libitum fed control and starved rats, the latter an animal model which is characterized by low circulating levels of endogenous GH and IGF-I. Adult male rats were fed ad libitum (C) or food-deprived (S) for 72 hours; rats in either C or S groups were treated with systemic administration of rhGH and rhIGF-I for 3 days. GHRH, SRIF and GH mRNA levels were evaluated by Northern and slot blot hybridization. Administration of rhGH (250 micrograms/kg/twice daily, sc) induced a significant inhibition of GHRH and a significant stimulation of SRIF mRNA levels in C rats; GH treatment was, however, ineffective on both neuropeptide mRNA levels in the S group. Continuous infusion of rhIGF-I (300 micrograms/kg/day, sc) induced a significant increase of SRIF levels in both C and S rats but did not modify GHRH mRNA levels in either group. In the pituitary, GH mRNA levels followed a pattern very similar to that of GHRH. These results provide evidence for a direct role of GH in the inhibition of GHRH mRNA levels; IGF-I appears more involved in the direct stimulation of SRIF mRNA levels.
Ghigo
M C
MC
Dipartimento di Farmacologia, Università degli Studi di Milano, Italy.
Torsello
A
A
Grilli
R
R
Luoni
M
M
Guidi
M
M
Cella
S G
SG
Locatelli
V
V
Müller
E E
EE
D000818:Animals; D004435:Eating; D005508:Food Deprivation / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism; D007276:Injections, Intraventricular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013004:Somatostatin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone