Thyroid hormone controls the expression of insulin-like growth factor I receptor gene at different levels in lung and heart of developing and adult rats.
Thyroid hormone exerts profound effects on the insulin-like growth factors (IGFs)/IGF factor I receptor (IGF-IR) system through its action on the production of IGF-I peptide and IGF-binding proteins. Most of these actions are mediated by the direct control of pituitary GH gene by thyroid hormone. In this work, we have analyzed the possible effect of hypothyroidism on the expression of IGF-IR gene, both in adult and developing animals. Our results show that in the lung and heart, thyroid hormone exerts a negative effect on IGF-IR gene expression in the adult animals and during perinatal life (from day 15 onwards). This negative effect is exerted at different levels. In the heart, this regulation occurs at a pretranslational level, indicated by the fact that parallel changes in the number of membrane IGF-I receptors and IGF-IR transcripts were observed, whereas in lung, no effect of thyroid hormone was noted in the amount of IGF-IR transcripts, suggesting a translational or posttranslational control. GH does not seem to mediate T3 effects on this gene. In contrast, retinoic acid increases the expression of IGF-IR gene at a transcriptional or posttranscriptional level in adult lung and heart. Because the IGFE/ IGF-IR system is depressed in hypothyroid animals, the specific increase in the number of IGF-IRs in the lung and heart of these animals could represent a mechanism to ameliorate the negative effects of hypothyroidism on these important organs.
Moreno
B
B
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Rodríguez-Manzaneque
J C
JC
Pérez-Castillo
A
A
Santos
A
A
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000502:physiology*; D019382:Human Growth Hormone / Q000494:pharmacology; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017451:Receptors, Somatomedin / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D014284:Triiodothyronine; D019382:Human Growth Hormone; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I