Regulation of lysosomal sulfate transport by thyroid hormone.
Sulfate transport was examined in rat liver lysosomes that were isolated from thyroid hormone-treated, thyroidectomized, and control animals. Sulfate uptake was significantly decreased in lysosomes from animals that had received intraperitoneal T3 (3,5,3'-triiodothyronine) at a dose of 20 micrograms/100 g body weight. The effect of T3 was maximal by 24 h post-injection and resulted in marked decreases in both Vmax (control: 155 +/- 33 pmol/unit of beta-hexosaminidase/30 s versus T3 treated: 24 +/- 7 pmol/unit of beta-hexosaminidase/30 s) and Km (control: 213 +/- 34 microM versus T3 treated: 92 +/- 6 microM). Thyroidectomy was associated with a significant increase in Vmax (control: 250 pmol/unit of beta-hexosaminidase/30 s versus thyroidectomized: 564 pmol/unit of beta-hexosaminidase/30 s), while Km was not significantly affected. The effect of thyroid hormone on lysosomal sulfate transport appeared to be relatively specific. In contrast to its effect on sulfate transport, T3 treatment had no effect on the uptake of either glucose or N-acetylglucosamine by rat liver lysosomes. Lysosomal pH, acidification in response to Mg/ATP, and the specific activities of alpha-L-iduronidase, beta-hexosaminidase, beta-D-glucosidase, and acid phosphatase were unaffected by T3 administration. Incubation of T3 with lysosomes from control animals had little or no effect on sulfate transport. Treatment of isolated lysosomes with either protein kinase A or alkaline phosphatase resulted in modest stimulation of transport. Thus, T3 does not appear to regulate transport by either direct interaction with the lysosomal transporter or protein kinase A-mediated phosphorylation. The exact mechanism for the inhibitory effect of T3 on lysosomal sulfate transport remains to be determined.
Chou
H F
HF
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90502.
Passage
M
M
Jonas
A J
AJ
D000818:Animals; D001692:Biological Transport; D005260:Female; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism*; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology*
D013431:Sulfates; D014284:Triiodothyronine; D005947:Glucose