Dexamethasone increases growth hormone receptor messenger ribonucleic acid levels in liver and growth plate.
Glucocorticoid inhibits linear growth and renders target tissues, particularly liver and growth plate, insensitive to GH. We hypothesized that glucocorticoid-induced GH insensitivity is due to decreased gene expression of the GH receptor at the messenger RNA (mRNA) level. To test this hypothesis, we treated 4.5-wk-old male rabbits (n = 6-9 per group) with ip dexamethasone or vehicle and measured GH receptor mRNA levels (by RNase protection assay) and serum GH-binding protein levels (by radioimmunoprecipitation assay). Contrary to our hypothesis, dexamethasone administered in growth-suppressing doses did not decrease GH receptor mRNA levels in liver or growth plate. Instead a tissue-specific stimulation of GH receptor mRNA levels was observed. The dose-response relationship of this effect was biphasic, since the lower growth-suppressing dose of dexamethasone (0.1 mg/kg.day) caused the greater increase in GH receptor mRNA levels, whereas the higher growth-suppressing dose (4 mg/kg.day) had less effect. The dexamethasone-induced increase in GH receptor mRNA was observed in growth plate and liver, target tissues important for linear growth, but not in kidney. Serum GH-binding protein levels also showed a stimulatory response to dexamethasone treatment, with a biphasic dose-response relationship. These data suggest that glucocorticoid-induced GH insensitivity cannot be explained by decreased GH receptor mRNA levels. To the contrary, dexamethasone causes a tissue-specific stimulation in GH receptor mRNA levels with a biphasic dose-response relationship.
Heinrichs
C
C
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Yanovski
J A
JA
Roth
A H
AH
Yu
Y M
YM
Domené
H M
HM
Yano
K
K
Cutler
G B
GB
Baron
J
J
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D006132:Growth Plate / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D011986:Receptors, Somatotropin / Q000235:genetics*; D013997:Time Factors
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D003907:Dexamethasone