Triiodothyronine down-regulates thyrotropin-releasing hormone (TRH) synthesis and decreases pTRH-(160-169) and insulin releases from fetal rat islets in culture.
TRH is localized with insulin in beta-cells. It is synthesized as a prohormone containing five copies of TRH and seven cryptic peptides, including pro (p)-TRH-(160-169). Thyroid hormone regulates the expression of several genes encoding peptide hormones. We found that circulating T3 concentrations were inversely correlated with TRH levels in two physiopathological situations. There are low concentrations of circulating thyroid hormone and very high concentrations of TRH and pTRH-(160-169) during development, and experimental hypothyroidism results in higher concentrations of prepro (pp)-TRH messenger RNA (mRNA) and TRH content in the adult rat pancreas than are present in the euthyroid pancreas. The present study was carried out to investigate the interaction between T3 and pancreatic TRH during the functional maturation of islets in culture and to validate the data obtained in vivo. T3 decreases ppTRH mRNA in islets in a dose-dependent manner. The primary impact of T3 on islet function may be mediated by ppTRH mRNA, as short term T3 treatment had no effect. Long term T3 treatment reduced the islet TRH content and the amounts of pTRH-(160-169) and insulin released. This secretory pattern and coordinated regulation of pTRH-(160-169) and insulin suggests that pTRH-(160-169) plays a specific role in the regulation of insulin secretion.
Fragner
P
P
INSERM U-30, Mécanisme d'Action Cellulaire des Hormones, Hôpital Necker Enfants Malades, Paris, France.
Ladram
A
A
Aratan de Leon
S
S
D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000196:embryology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D014284:Triiodothyronine; C057639:prepro-thyrotropin releasing hormone (160-169); D013973:Thyrotropin-Releasing Hormone