Kinetics of red blood cell T3 uptake in hypothyroidism with or without hormonal replacement, in the rat.
L-triiodothyronine (L-T3) is taken up and accumulated into red blood cells (RBC) by means of a specific carrier-mediated system. The aim of this study was to evaluate the reactivity of this system in relation to induced alterations in thyroid hormone (TH) supply. We investigated the kinetic parameters (Vmax, maximal velocity and Km, Michaelis constant) of washed-RBC L-T3 uptake 1) in thyroidectomized (TXT) rats, 2) in TXT rats administered with low doses of L-T4 (15 microg/kg/day x 14) to restore normal serum TH levels (REPL), 3) in TXT rats administered with high doses of L-T4 (200 microg/kg/day x 14) to achieve a large increase in serum TH levels (HIGH). Serum free T3 and T4 levels were significantly decreased in TXT rats (2.4 and 8.8 fold, respectively), not different in REPL rats and significantly increased in HIGH rats (2.4 and 3 fold, respectively) compared to sham-operated rats (SHAM). Both kinetics of RBC L-T3 uptake were significantly increased in TXT rats (Vmax+/-SE in pmol/min/10(8) cells=235.1+/-11.1, p<0.05 and Km+/-SE in nM=190.1+/-9.0, p<0.05), not different in REPL rats (Vmax=1 84.8+/-7.6 and Km=151.9+/-7.1) and significantly decreased in HIGH rats (Vmax=168.0+/-4.1, p<0.01 and Km=131.9+/-4.6, p<0.01) compared to SHAM rats (Vmax=197.7+/-5.8 and Km=160.9+/-6.1). These results show that kinetics of RBC L-T3 uptake are modified in response to defect or excess in circulating TH levels. Since RBC play likely a role of a buffer system, the changes in carrier-mediated influx of L-T3 could be seen as a compensatory mechanism that counteract the disturbances in the TH availability for the target tissues.
Moreau
X
X
INSERM U38, Fonction Thyroïdienne et Régulations, Faculté de Médecine, Marseille, France.
Lejeune
P J
PJ
Jeanningros
R
R
D000818:Animals; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D020249:Hormone Replacement Therapy; D007037:Hypothyroidism / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000097:blood*; D013965:Thyroidectomy; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D014284:Triiodothyronine / Q000097:blood*
D013963:Thyroid Hormones; D014284:Triiodothyronine; D013974:Thyroxine