Glucocorticoids regulate pituitary growth hormone secretagogue receptor gene expression.
Glucocorticoids regulate growth hormone (GH) secretion by modulating both hypothalamic and pituitary function. At the level of the pituitary, glucocorticoids increase GH and GH-releasing hormone receptor (GHRH-R) gene expression. To test if glucocorticoids might also regulate the pituitary expression of the recently identified GH secretagogue (GHS) receptor, GHS-R; adult male rats were adrenalectomized or sham operated, and treated with the synthetic glucocorticoid (dexamethasone, 200 microg/day) or vehicle for 8 days. Pituitary GHS-R mRNA levels were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Adrenalectomy decreased pituitary GHS-R mRNA to 45% of vehicle-treated, sham-operated rats (P < 0.05). Administration of dexamethasone increased GHS-R mRNA levels in sham-operated as well as in adrenalectomized rats (199 +/- 24% (P < 0.05) and 369 +/- 48% (P < 0.01) of vehicle-treated controls). Addition of dexamethasone to primary rat pituitary cell cultures increased GHS-R mRNA levels in a dose- and time-dependent manner while the transcriptional inhibitor, actinomycin D, completely blocked the stimulatory action of dexamethasone. Taken together, these results suggest glucocorticoids directly increase pituitary GHS-R mRNA levels by stimulating GHS-R gene transcription.
Tamura
H
H
Department of Medicine, Nippon Medical School, Tokyo, Japan.
Kamegai
J
J
Sugihara
H
H
Kineman
R D
RD
Frohman
L A
LA
Wakabayashi
I
I
D000315:Adrenalectomy; D000818:Animals; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D013997:Time Factors
D005938:Glucocorticoids; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D003609:Dactinomycin; D003907:Dexamethasone; C048250:somatotropin releasing hormone receptor