ABSTRACT
The anterior pituitary contains abundant type II iodothyronine 5'-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that it exists in other cell types, including somatotropes and lactotropes. Here we investigated the potential of D2 to mediate thyroid hormone regulation of growth hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid states GH mRNA levels are stimulated by triiodothyronine (T(3)) generated via D1, whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is more responsive to tetraiodothyronine (T(4)) in a propylthiouracil-insensitive, reverse T(3)-suppressible manner. Under short-term hyperthyroid conditions, GH levels correlate with plasma T(3); in contrast, the correlation is not observed in hypothyroidism, a condition in which plasma T(3) levels are too low to account for the response. These results add support to the concept that D2 is present in the pituitary and that the enzyme plays an important role in mediating stimulation of GH by thyroid hormones, particularly in hypothyroid states in which they could alleviate the impact of hypothyroxinemia on GH secretion.
Subject(s)
Hypothyroidism/enzymology , Iodide Peroxidase/metabolism , Pituitary Gland/cytology , Pituitary Gland/enzymology , Adaptation, Physiological , Animals , Blotting, Northern , Hypothyroidism/pathology , Hypothyroidism/physiopathology , Male , RNA, Messenger/biosynthesis , Rats , Rats, Wistar , Thyroxine/biosynthesis , Triiodothyronine/biosynthesis , Iodothyronine Deiodinase Type IIABSTRACT
Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03% methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.
Subject(s)
Gene Expression , Growth Hormone/genetics , Thyroid Hormones/physiology , Animals , Blotting, Northern , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Thyroid Hormones/genetics , Thyroid Hormones/metabolism , Time Factors , Transcription, Genetic , Triiodothyronine, Reverse/administration & dosageABSTRACT
Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03 methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.