Decreased anterior pituitary T3 nuclear receptors in a Walker 256 carcinoma-bearing rat model of nonthyroidal disease.
Rats bearing the Walker 256 carcinoma have decreased pituitary nuclear T3 but normal pituitary TSH content and response to experimental hypothyroidism. To elucidate further the role of T3 receptor occupancy and biological response in the tumor-bearing rat model of nonthyroidal disease, we measured the concentration of T3 nuclear receptors, rTSH and rGH and beta-TSH mRNA and GH mRNA in the anterior pituitary of euthyroid rats bearing the Walker 256 carcinoma. The abundance of T3 nuclear receptors was decreased in tumor-bearing rats and was associated with a decrease in mRNA content for beta-TSH and GH. alpha-tubulin mRNA was decreased to a comparable degree. The pituitary content of rTSH and rGH was, however, the same as in control animals. Since tumor rats have normal regulation of TSH secretion by thyroid hormone, the present findings suggest that TSH secretion in T rats is maintained by a lower T3 nuclear receptor occupancy than in controls. The decrease in beta-TSH mRNA may precede a decrease in TSH synthesis and changes in pituitary TSH stores. Since the decrease in GH mRNA was comparable to the decrease in alpha-tubulin mRNA, it does not appear to be specifically related to decreased T3 nuclear receptor occupancy. We conclude that, in the tumor-bearing rat model of nonthyroidal disease, decreases in beta-TSH mRNA occur despite a decreased T3 receptor occupancy. Both thyroid-dependent and thyroid-independent factors may be involved in regulating beta-TSH mRNA.
Hupart
K H
KH
Department of Medicine, Montefiore Medical Center, Bronx, New York.
DeFesi
C R
CR
Katz
C P
CP
Shapiro
L E
LE
Surks
M I
MI
D000818:Animals; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011986:Receptors, Somatotropin / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000378:metabolism
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D011988:Receptors, Thyroid Hormone; D011989:Receptors, Thyrotropin