Expression of the growth hormone gene and the pituitary-specific transcription factor GHF-1 in diabetic rats.
Diabetes in the rat is associated with poor growth and decreased GH in the pituitary. In this study we have examined whether this reduction reflects an impairment of GH gene expression. Diabetes was induced by the administration of streptozotocin (7 mg/100 g BW), and 18 days later, GH content, GH mRNA, and GH transcription rate were determined. GH mRNA levels were reduced by more than 80% in the pituitaries of diabetic rats, which had a similarly reduced GH content. The differences observed in transcription fully account for the changes in mRNA concentration, since the transcription rate of the gene was also reduced by a factor of 10 in the diabetic pituitaries. Insulin therapy (3 U/15 days) partially restored these parameters. The expression of the specific transcription factor GHF-1/Pit-1 in diabetic rats was also analyzed. Both GHF-1 mRNA levels and the binding of nuclear proteins to an oligodeoxynucleotide conforming to the GHF-1 proximal binding site in the promoter of the GH gene were normal in the diabetic pituitaries, thus excluding the possibility that decreased availability of this factor could be responsible for the decreased GH transcription. Since diabetes produced an approximately 3-fold reduction of circulating T3, the potential role of thyroid hormones on GH gene expression was also evaluated in thyroidectomized and thyroidectomized diabetic rats. Thyroidectomy decreased GH and GH mRNA to less than 5% of the values found in intact animals, and a single saturating injection of T3 (250 micrograms/100 g BW) resulted in a 8- to 10-fold induction of GH mRNA after 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Bedo
G
G
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Santisteban
P
P
Jolin
T
T
Aranda
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D001835:Body Weight; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D013006:Growth Hormone / Q000235:genetics*; D007328:Insulin / Q000627:therapeutic use; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013965:Thyroidectomy; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology
D004268:DNA-Binding Proteins; D007328:Insulin; D009838:Oligodeoxyribonucleotides; C494186:Pou1f1 protein, rat; D012333:RNA, Messenger; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D014284:Triiodothyronine; D013006:Growth Hormone