Thyroid hormone status correlates inversely with expression of the growth hormone receptor gene in rats immediately after birth.
To investigate the role of thyroid hormone in the expression of the gene encoding the growth hormone receptor (GHR) and growth hormone binding protein (GHBP), fetal rats were made hypothyroid through the administration of the goitrogen methimazole to the mother. Euthyroidism was maintained in the mother by concurrent administration of L-thyroxine, which crosses the placenta poorly. Methimazole and L-thyroxine were continued in the mothers until weaning. After birth, groups of methimazole-treated or control pups were sacrificed immediately and at one, two, three, four, five, or six weeks after birth. In each group, weight was recorded, blood was obtained for measurement of T4, thyroid stimulating hormone (TSH), and growth hormone (GH), and liver tissue was obtained for quantitation of GHR and GHBP mRNA. The methimazole-treated pups were demonstrated to be hypothyroid, with markedly higher TSH and lower T4 concentrations, until weaning occurred between weeks three and four, after which they transiently became hyperthyroid at week five (T4 = 17 +/- 5 micrograms/dL vs. 6 +/- 0.5 micrograms/dL for controls) but returned to an euthyroid state at week six. In control pups the relative abundance of GHR and GHBP mRNA increased abruptly in week one, and increased three to four fold over the ensuing six weeks. Immediately after birth, the hypothyroid pups expressed significantly more GHR and GHBP mRNA than did the controls (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213.
D A
DA
Stephan
R K
RK
Menon
B
B
Franz
M A
MA
Sperling
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000378:metabolism; D007037:Hypothyroidism / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008713:Methimazole; D011247:Pregnancy; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D051381:Rats; D011986:Receptors, Somatotropin / Q000032:analysis / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*
D002352:Carrier Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D008713:Methimazole; D013972:Thyrotropin; D013006:Growth Hormone; D013974:Thyroxine; C051815:somatotropin-binding protein