The modulation by 3,5,3'-triiodothyronine (T3) of pituitary T3 nuclear receptors in hypothyroid rats is inhibited by cycloheximide.
The density of T3 nuclear receptors is known to vary with tissues and physiopathological conditions, but the factors involved in their regulation are still unknown. We have previously shown in the anterior pituitary gland that T3 modulates its own receptors; the density of T3 receptors in hypothyroid rats is half that in normal rats, and one injection of T3 is able to restore normal density of T3 receptors within 1-3 h. To determine whether T3 has a direct action on the synthesis of its nuclear receptor, the effect of cycloheximide (Cy) on T3-induced nuclear receptor was studied. In addition, the relationship between the density of pituitary T3 receptors and the secretion of TSH in different thyroid states was examined. In normal rats one injection of Cy (0.5-8 mg/100 mg BW) induced within 3 h a dose-dependent reduction in the density of pituitary T3 receptors as well as an important decrease in plasma TSH, with no changes in T4, T3, or pituitary TSH content. In hypothyroid rats the 50% decrease in the density of pituitary T3 receptors was not further reduced by 1 mg Cy. However, when the same dose of Cy was given 30 min before T3 it completely inhibited the induction by T3 of its receptors. When Cy was given 30 min or 1 h after T3 the inhibition was only partial. An inverse correlation was found between the density of T3 receptors in the pituitary gland and plasma TSH (r = -0.8128) in all experimental groups except those treated with Cy; this drug had an inhibitory effect on both TSH secretion and the density of receptors. The present data, therefore, support the view that T3 in the pituitary gland may induce the synthesis of its own nuclear receptors and that the density of T3 receptors is also involved in the control of TSH secretion.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013972:Thyrotropin; D003513:Cycloheximide; D013974:Thyroxine