Age- and growth hormone-induced alterations in renal sulfate transport.
The effects of growth hormone (GH) treatment on renal sodium sulfate cotransport (NaSi-1) were studied in adult (9-10 months) and old (22-23 months) male Fischer 344 rats. All animals received twice-daily s.c. injections of recombinant human GH (hGH; 4 mg/kg) for up to 6 days. Animals were sacrificed by exsanguination on days 0, 1, 2, 3, 4, 5, and 6. Kidneys were removed, and kidney cortex was trimmed immediately and used for RNA and membrane preparations. Plasma hGH concentrations were significantly lower in old rats during the hGH treatment (P <.05). Insulin-like growth factor-I (IGF-I) levels were significantly increased and remained stable after day 2 of hGH treatment in both age groups (P <.05). There was no significant difference in plasma IGF-I levels between age groups. Plasma IGF-I binding protein 3 (IGFBP-3) concentrations were significantly higher in 9- to 10-month-old rats compared with that in 22- to 23-month-old animals (P <.001). There were no significant differences in plasma IGFBP-3 concentrations between days of hGH treatment. The NaSi-1 mRNA levels were significantly lower in 22- to 23-month-old rats compared with that in 9- to 10-month-old animals (P <.001). The NaSi-1 mRNA levels were significantly increased on days 2 and 3 of hGH treatment (P <.05) and then gradually decreased to the control value. The NaSi-1 protein levels in old animals (22-23 months) were also significantly lower than that of 9- to 10-month-old animals and were significantly increased from day 2 of hGH treatment, reaching a maximum level on day 3 or 4 and then returning to the baseline level in both age groups. From these results, it was concluded that 1) NaSi-1 mRNA and protein levels are lower in old animals and increase in both adult and aged rats after hGH treatment, 2) plasma IGF-I levels are similar in adult and aged rats and increase after hGH treatment, and 3) plasma IGFBP-3 levels are lower in old rats and remain unchanged after hGH treatment.
Sagawa
K
K
Department of Pharmaceutics, State University of New York at Buffalo, Amherst, New York, USA.
Han
B
B
DuBois
D C
DC
Murer
H
H
Almon
R R
RR
Morris
M E
ME
D000375:Aging / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D019382:Human Growth Hormone / Q000097:blood / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000493:pharmacokinetics; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000378:metabolism*; D027981:Symporters
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D012964:Sodium