Dose-Dependent Depletion of Nuclear Receptors by L-triiodothyronine: Evidence for a Role in Induction of Growth Hormone Synthesis in Cultured GH1 Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1976-11, Vol.73 (11), p.3877-3881
• Main Authors: Samuels, Herbert H., Stanley, Frederick, Shapiro, Lawrence E.
• Format: Article
• Language: English
• Subjects: Cell culture techniques; Cell Line; Cell lines; Cell nucleus; Cell Nucleus - metabolism; Cultured cells; Dose-Response Relationship, Drug; Flasks; Growth Hormone - biosynthesis; Growth hormones; Hormones; Kinetics; Nuclear receptors; Receptors; Receptors, Cell Surface - metabolism; Thyroid hormones; Time Factors; Triiodothyronine - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.73.11.3877

The relationship between the binding of L-triiodothyronine (T3) to nuclear receptors and the induction of growth hormone synthesis was examined in cultured GH1 cells, a rat pituitary cell line. After 24 hr, T3 induced a maximal 4-fold increase in the rate of growth hormone synthesis; the T3 concentration that induced a half-maximal increase was 0.22 nM. The biologic dose-response curve was shifted to the left of the receptor occupancy curve (Kd = 0.5 nM) by a factor of approximately 2 when receptor binding was examined for 4 hr but showed a significantly closer agreement when examined for the same 24-hr period as the biologic response. This shift in the fractional occupancy curve is not due to further equilibration but occurs as a result of a time- and dose-dependent depletion of the nuclear receptor by T3.