Dose-dependent depletion of nuclear receptors by L-triiodothyronine: evidence for a role in induction of growth hormone synthesis in cultured GH1 cells.
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 wynthesis; 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.
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000096:biosynthesis*; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism*
D011956:Receptors, Cell Surface; D014284:Triiodothyronine; D013006:Growth Hormone