Mechanism of hypothyroidism action on insulin-like growth factor-I and -II from neonatal to adult rats: insulin mediates thyroid hormone effects in the neonatal period.
The effects of thyroid hormone deficiency on serum levels and liver messenger RNA (mRNA) expression of insulin-like growth factors (IGFs) were studied in neonatal (until 20 days of life), weaned (22-37 days), and adult (72-87 days) rats, short periods (5, 10, and 15 days) after thyroidectomy (T). Serum levels and liver mRNA expression of IGF-I, plasma and pituitary GH, plasma insulin, and glycemia were measured in all populations; and serum levels and liver mRNA expression of IGF-II were measured only in the neonatal populations. Surprisingly, plasma insulin and GH and serum and liver mRNA expression of IGF-I were found elevated in T neonatal rats, and they decreased in weaned and adult rats and in neonatal rats rendered hypothyroid by mercapto-1-methylimidazole (MMI) treatment (MMI-hypothyroid). T and MMI-treatment of neonatal rats disturbed the normal pattern of progressive decrease of IGF-II with age. A positive correlation between insulin and IGF-I and a poor correlation between GH and IGF-I were found in both hypothyroid neonates (T and MMI-hypothyroid). On the contrary, a positive correlation between GH and IGF-I and a poor correlation between insulin and IGF-I were found for control and T adult rats. Because plasma insulin and GH changed in the same direction in all groups, insulin secretion in T neonatal was suppressed by streptozotocin, and insulin was given to T adult rats. The combined results of these experiments support the idea that the effects of thyroid hormones on IGF-I secretion are age-dependent, and they are mediated mainly by insulin during the neonatal period and by GH during adulthood.
Ramos
S
S
Instituto de Bioquímica (Centro Mixto Consejo Superior de Investigaciones Cientificas-Universidad Complutense de Madrid), Facultad de Farmacia, Ciudad Universitaria, Spain.
Goya
L
L
Alvarez
C
C
Pascual-Leone
A M
AM
D000375:Aging / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn / Q000097:blood* / Q000254:growth & development; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D007093:Imidazoles; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D007329:Insulin Antagonists / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000032:analysis* / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D013963:Thyroid Hormones / Q000502:physiology; D013965:Thyroidectomy; D014886:Weaning
D007093:Imidazoles; D007328:Insulin; D007329:Insulin Antagonists; D012333:RNA, Messenger; D013963:Thyroid Hormones; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C018100:1-methylimidazole