title: Dexamethasone increases growth hormone receptor messenger ribonucleic acid levels in liver and growth plate.
abstract: 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.
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: C
authors.initials: C
authors.lastname: Heinrichs
authors.forename: J A
authors.initials: JA
authors.lastname: Yanovski
authors.forename: A H
authors.initials: AH
authors.lastname: Roth
authors.forename: Y M
authors.initials: YM
authors.lastname: Yu
authors.forename: H M
authors.initials: HM
authors.lastname: Domené
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: G B
authors.initials: GB
authors.lastname: Cutler
authors.forename: J
authors.initials: J
authors.lastname: Baron
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D003907:Dexamethasone