Thyroid hormone export varies among primary cells and appears to differ from hormone uptake.
We characterized T3 efflux in primary cultures of cells derived from human placenta, neonatal rat cardiac myocytes, and rat inner medullary collecting ducts (IMCD). The T3 efflux rate was highest in placenta cells, followed by ventriculocytes, atriocytes, and IMCD cells. Verapamil reversibly blocked [125I]T3 efflux in these cells in a manner that correlated with their T3 efflux rate. Thus, verapamil inhibition of [125I]T3 efflux in placenta cells led to a 432% increase in the [125I]T3 content compared with 33% increase in IMCD cells. Several unlabeled iodothyronines, but not TRIAC, differentially blocked [125I]T3 efflux such as (T4 > T3 > rT3 = D-T3 > D-T4) in placenta cells and (T4 > rT3 = D-T4 = T3 > D-T3) in ventriculocytes, suggesting tissue-specific differences in the carriers/transporters responsible for T3 efflux. This hypothesis draws further support from the fact that D-T3 inhibited [125I]T3 efflux in placenta cells, but not in ventriculocytes. TRIAC did not affect T3 efflux in ventriculocytes or placenta cells, but it greatly inhibited [125I]T3 uptake in these cells, suggesting that [125I]T3 uptake and efflux mechanisms are distinct and appear to be mediated by distinct carrier/transporter proteins. Collectively, these data suggest that differences in thyroid hormone transport in target cells may provide an important mechanism for regulating hormone action in a tissue-specific fashion.
Neves
Francisco A R
FA
Department of Pharmaceutical Sciences, University of Brasília, Brasília, DF 70910-900, Brazil.
Cavalieri
Ralph R
RR
Simeoni
Luiz A
LA
Gardner
David G
DG
Baxter
John D
JD
Scharschmidt
Bruce F
BF
Lomri
Noureddine
N
Ribeiro
Ralff C J
RC
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002823:Chorion / Q000166:cytology / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013963:Thyroid Hormones / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007202:Indicators and Reagents; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014700:Verapamil