Differential regulation of the growth hormone receptor gene: effects of dexamethasone and estradiol.
GH receptor (GHR) expression differs during development between central and peripheral tissues. Peripheral GHR expression is known to be sensitive to gonadal and adrenal steroids, but little is known about their effects on GHR in the central nervous system. We have now studied the effects of estradiol (E2) or dexamethasone on GHR expression in rat arcuate nucleus (ARC) and hippocampus, using quantitative in situ hybridization. Dexamethasone, which strongly down-regulates hepatic GHR expression, had no effect on central GHR transcript abundance, whereas E2 treatment, which stimulates hepatic GHR expression, significantly reduced ARC GHR messenger RNA (mRNA) levels. E2 also increased somatostatin (SS) expression significantly in both ARC and periventricular nuclei but did not reduce ARC GH-releasing hormone (GHRH) mRNA levels. Ovariectomy stimulated GHR and GHRH mRNA levels in the ARC, whereas it lowered ARC SS expression. E2 replacement in ovariectomized animals restored GHRH and SS mRNA levels to control values. Hippocampal GHR mRNA transcripts showed the same response to these endocrine manipulations as seen in the ARC. The induction of hepatic GHR expression by E2 is known to involve the transcription of an alternate 5' untranslated first exon, GHR1. This was readily detectable in the liver using a specific GHR1 probe but could not be detected in any CNS area. Our results show that GHR expression in the CNS is sensitive to regulation by peripheral steroids but that CNS and hepatic expression of GHR is differentially regulated by the same treatments.
Bennett
P A
PA
University of Bristol, Department of Medicine, Bristol Royal Infirmary, United Kingdom. p-bennet@nimr.mrc.ac.uk
Levy
A
A
Carmignac
D F
DF
Robinson
I C
IC
Lightman
S L
SL
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D005938:Glucocorticoids; D011986:Receptors, Somatotropin; D004958:Estradiol; D003907:Dexamethasone