L-triiodothyronine (T3) regulates cellular growth rate, growth hormone production, and levels of nuclear T3 receptors via distinct dose-response ranges in cultured GC cells

Yitzchak Halperin, Martin I. Surks, Lawrence E. Shapiro

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Abstract

Cultured rat somatotrophic cells have been useful models for the study of thyroid hormone action. A consensus of previous reports has indicated that approximately 0.2 nM T3 results in 50% occupancy of T3 nuclear receptors as well as halfmaximal stimulation of several T3 responses. To characterize the nature of thyroid hormone responses in GC cells, we studied in detail the T3 dose relationships between nuclear receptor occupancy and three thyroid hormone responses (cell growth, GH production, and T3 nuclear receptor regulation). The dose response to T3 for each parameter was unique, and none was identical to the dose response for receptor occupancy. Respective T3 concentrations and percentage of T3 nuclear receptor occupancy resulting in 50% of the maximal response for GC cell growth were 0.05 ± 0.02 nM and 15 ± 3% (four experiments), 0.15 ± 0.04 nM and 27 ± 3% for GH production (three experiments), and 2.1 nM and 69% for down-regulation of T3 nuclear receptors (two experiments). We conclude that the dose response for occupancy of the T3 nuclear receptor covers a wide range of T3 concentrations. Within the wide dose-response range for nuclear occupancy a spectrum of biological responses are regulated by distinct thyroid hormone dose ranges. These data suggest that the impact of T3 nuclear receptor occupancy on T3 responses might be variable and that the mechanisms involved may be clarified through studies in GC cells.

Original languageEnglish (US)
Pages (from-to)2321-2326
Number of pages6
JournalEndocrinology
Volume126
Issue number5
StatePublished - May 1990

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Thyroid Hormone Receptors
Triiodothyronine
Cytoplasmic and Nuclear Receptors
Growth Hormone
Cultured Cells
Thyroid Hormones
Growth
Down-Regulation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

L-triiodothyronine (T3) regulates cellular growth rate, growth hormone production, and levels of nuclear T3 receptors via distinct dose-response ranges in cultured GC cells. / Halperin, Yitzchak; Surks, Martin I.; Shapiro, Lawrence E.

In: Endocrinology, Vol. 126, No. 5, 05.1990, p. 2321-2326.

Research output: Contribution to journalArticle

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abstract = "Cultured rat somatotrophic cells have been useful models for the study of thyroid hormone action. A consensus of previous reports has indicated that approximately 0.2 nM T3 results in 50{\%} occupancy of T3 nuclear receptors as well as halfmaximal stimulation of several T3 responses. To characterize the nature of thyroid hormone responses in GC cells, we studied in detail the T3 dose relationships between nuclear receptor occupancy and three thyroid hormone responses (cell growth, GH production, and T3 nuclear receptor regulation). The dose response to T3 for each parameter was unique, and none was identical to the dose response for receptor occupancy. Respective T3 concentrations and percentage of T3 nuclear receptor occupancy resulting in 50{\%} of the maximal response for GC cell growth were 0.05 ± 0.02 nM and 15 ± 3{\%} (four experiments), 0.15 ± 0.04 nM and 27 ± 3{\%} for GH production (three experiments), and 2.1 nM and 69{\%} for down-regulation of T3 nuclear receptors (two experiments). We conclude that the dose response for occupancy of the T3 nuclear receptor covers a wide range of T3 concentrations. Within the wide dose-response range for nuclear occupancy a spectrum of biological responses are regulated by distinct thyroid hormone dose ranges. These data suggest that the impact of T3 nuclear receptor occupancy on T3 responses might be variable and that the mechanisms involved may be clarified through studies in GC cells.",
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