Endocrinology, Vol 100, 807-813, Copyright © 1977 by Endocrine Society
Stimulation of thyroxine-binding globulin synthesis by isolated rhesus monkey hepatocytes after in vivo beta-estradiol administration
D Glinoer, MC Gershengorn, A Dubois and J Robbins
Clinical Endocrinology Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, Bethesda, Maryland 20014.
The rate of in vitro production of thyroxine-binding globulin (TBG) was
studied in hepatocytes isolated from 6 control rhesus monkeys (serum TBG:
19.6 +/- 0.5 micrograms/ml; mean +/- SE) and 6 monkeys treated for 4-5
weeks with beta-estradiol (E2) (serum TBG: 45.1 +/- 1.8 micrograms/ml).
Incorporation of [3H]leucine into intracellular soluble and particle-bound
TBG, and into secreted TBG was determined for incubation periods up to 9 h.
TBG was purified by affinity chromatography and measured by specific
immunoprecipitation. The absolute amount of [3H]TBG and the ratio of
[3H]TBG to total labeled protein in the same fraction were 3-fold higher in
the particulate fraction and in the incubation medium of hepatocytes
isolated from E2- treated monkeys. In separate experiments, TBG
accumulation in the medium was measured for periods up to 19 h by
radioimmunoassay. A 2.4- fold increase was observed with hepatocytes from
E2-treated monkeys (3.48 ng TBG/h/10(7) cells, compared to 1.46 in
controls). Correction of the production rates for the number of cells
surviving during the incubation, and assuming 10.2 x 10(9) cells per liver,
gave TBG production rates of 250 micrograms/liver/day in hepatocytes from
E2- treated monkeys and 104 micrograms/day in hepatocytes from control
monkeys. These experiments demonstrate that estrogen increases in vitro
synthesis and secretion of TBG by isolated hepatocytes. The observed 2.4 to
3-fold increase was similar to the 2.9-fold increase in TBG production
measured in vivo by kinetic analysis of TBG metabolism.