Dexamethasone increases growth hormone (GH)-releasing hormone (GRH) receptor mRNA levels in cultured rat anterior pituitary cells.
To examine the effects of glucocorticoid (GC) on growth hormone (GH)-releasing hormone (GRH) receptor gene expression, a highly-sensitive and quantitative reverse-transcribed polymerase chain reaction (RT-PCR) method was used in this study. Rat anterior pituitary cells were isolated and cultured for 4 days. The cultured cells were treated with dexamethasone for 2, 6, and 24 h. GRH receptor mRNA levels were determined by competitive RT-PCR using a recombinant RNA as the competitor. Dexamethasone significantly increased GRH receptor mRNA levels at 5 nM after 6- and 24 h-incubations, and the maximal effect was found at 25 nM. The GC receptor-specific antagonist, RU 38486 completely eliminated the dexamethasone-induced enhancement of GRH receptor mRNA levels. Dexamethasone did not alter the mRNA levels of beta-actin and prolactin at 5 nM for 24 h, whereas GH mRNA levels were significantly increased by the same treatment. The GH response to GRH was significantly enhanced by the 24-h incubation with 5 nM dexamethasone. These findings suggest that GC stimulates GRH receptor gene expression through the ligand-activated GC receptors in the rat somatotrophs. The direct effects of GC on the GRH receptor gene could explain the enhancement of GRH-induced GH secretion.
Tamaki
M
M
First Department of Internal Medicine, Kagawa Medical School, Japan.
Sato
M
M
Matsubara
S
S
Wada
Y
Y
Takahara
J
J
D000199:Actins / Q000235:genetics; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D017931:DNA Primers; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011388:Prolactin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*
D000199:Actins; D017931:DNA Primers; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D015735:Mifepristone; D003907:Dexamethasone; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D012194:RNA-Directed DNA Polymerase; C048250:somatotropin releasing hormone receptor