Effects of thyroid hormone and actinomycin D on phosphate uptake of brush-border membrane vesicles from kidney of rachitic rats.
It is generally accepted that 3,5,3'-triiodothyronine (T3) is responsible for most of the known physiological actions of thyroid hormone. Our new rachitogenic diets, deficient in both vitamin D and iodine and low in phosphorus (1.13% calcium and 0.14% phosphorus), induced typical rachitic changes in rats. To know the possible role of T3 on bone and phosphate (Pi) metabolism and its related biochemical and molecular mechanism, weanling male Wistar rats were fed this diet for 28 days, and then treated with 6 micrograms/100g BW of T3 and/or 60 micrograms/100g BW of actinomycin D intraperitoneally. After 2 hours of treatment, renal brush-border membrane vesicles (BBMV) were prepared according to the calcium precipitation method, and their Na(+)-dependent Pi uptake was analyzed by Lineweaver-Burk plots. Km value was not significantly altered by all these treatments. In contrast, Vmax value as a Pi uptake index was significantly increased in T3-treated rats compared with rachitic control. This increase was evident as less as 2 hr after T3 administration, so it was assumed that T3 stimulated the Pi uptake not by mediation of the de novo protein synthesis. However this increase was suppressed by administration of actinomycin D, and then this result suggests that the antirachitic effect of T3 is mediated by somehow de novo protein synthesis. After all, T3 acting as an antirachitic agent, the most likely possibility is that T3 provides favorable conditions for mineralization of bone by improving Pi transport in various types of cells, even under rachitogenic condition, at least of hypophosphatemic type, and correction of phosphate metabolism may be the most essential prerequisite for cure of this type of rickets.
Kishida
M
M
Second Department of Pathology, Osaka City University Medical School, Japan.
Umano
T
T
Kadoya
Y
Y
Motoda
T
T
Hashimoto
R
R
Shimazaki
M
M
Shimazu
A
A
D000818:Animals; D003609:Dactinomycin / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000493:pharmacokinetics*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012279:Rickets / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D010710:Phosphates; D014284:Triiodothyronine; D003609:Dactinomycin