Dose dependent depletion of nuclear receptors by L triiodothyronine: evidence for a role in induction of growth hormone synthesis in cultured GH1 cells

Abstract

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 approx. 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.