Pituitary Thyrotropin (TSH) Rebound Phenomenon and Kinetics of Secretion in the Goitrous Rat: Differential Effects of Thyroxine on Synthesis and Release of TSH1

Abstract

The protein metabolism and [3H]-uridine uptake of thyroid and adenohypophysis and the kinetics of pituitary TSH rebound (PTR) were studied in goitrous female rats (fed propylthiouracil, PTU: for 7-12 wk) following single, i.v. injections of L-thyroxine (T4: 0.8-200 .mu.g). Goitrogenesis was associated with reduced protein concentration and enhanced uptake of [3H]uridine in both glands. Plasma levels of TSH were invariably elevated, but stores in the adenohypophysis were consistently reduced. Small doses of T4 (4 .mu.g) induced significant TSH repletion in the pituitary within 2-6 h following injection. Accumulations of pituitary TSH to supranormal levels (15-fold increases) were achieved with 20 .mu.g T4 at 6 and 24 h; higher doses (100-200 .mu.g) inhibited the PTR at all time intervals tested (0.5-24 h). Administration of puromycin or actinomycin D did not influence the PTR. Protein content and labeled uridine uptake of the pituitary bore no apparent relationship to T4-induced TSH repletion in the gland. Blood clearance rate of exogenous rat TSH was measured prior to and during PTR. Plasma half-life was determined to be 13.6 and 19.9 min in euthyroid and chronically hypothyroid rats, respectively; it was not significantly altered from the latter during rebound (18.7 min). Calculations of theoretical TSH secretory rates prior to (50.5 .+-. 4.4 mU[m units]/h) and after rebound with 20 .mu.g T4 (25.4 .+-. 4.2 mU/h) revealed that the reaccumulation of TSH in the pituitary induced with T4 cannot be attributed solely to inhibition of release, but may also involve enhancement of synthesis. T4 administration at high dose levels inhibits both synthesis and release of TSH from pituitary thyrotrophs, whereas low critical doses of T4 suppress release, but augment synthesis and/or facilitate conformational change in a pituitary precursor(s) molecule which renders it detectable by bioassay.