Regulation of rat pancreatic nuclear triiodothyronine receptor by glucocorticoid.
The nuclear T3 receptors in rat pancreas exhibit a characteristic maturation pattern during development and are subjected to autologous regulation by thyroid hormones. To see if glucocorticoids also regulate T3 receptors in the pancreas, rats at various age groups were subjected to experimental conditions that altered their glucocorticoid status and the corresponding changes in nuclear T3 receptors, and exocrine enzymes in their pancreata were evaluated. Hydrocortisone administration to normal suckling and weaning rats did not change total T3 binding capacity or the dissociation constant as measured at 30 degrees C (Kd30). A significant increase in the degree of occupancy of the T3 receptor was found at 5-10 days after treatment with hydrocortisone (42.2 + 4.1% vs. 19.2 + 2.0%). T3 binding capacity and exocrine enzyme concentrations were significantly reduced in both adrenalectomized (Adx) pups and adults, indicating a continuous dependency on glucocorticoid from preweaning to adulthood. In adrenalectomized rat pups, either T4 or glucocorticoid replacement alone restored T3 binding capacity and exocrine enzyme concentrations. T4 and glucocorticoid were given together to Adx rats, the level of stimulation of both pancreatic T3 binding capacity and exocrine enzyme concentrations was found to be equal to the sum of the stimulation by each of these hormones when given alone. Furthermore, a good correlation was found between Bmax30 (Bmax measured at 30 degrees C, representing total sites) for T3 binding and exocrine enzyme activities in different groups following various experimental treatments. These findings provide further evidence that thyroxine can act directly on the rat pancreas presumably through the T3 receptor in regulating the postnatal development of the exocrine enzymes.
Lee
J T
JT
Department of Pediatrics, Children's Hospital, State University of New York, Buffalo.
Lebenthal
E
E
Lee
P C
PC
D000315:Adrenalectomy; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism
D005938:Glucocorticoids; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013974:Thyroxine; D006854:Hydrocortisone