Growth hormone-induced glomerular hyperfiltration is dependent on vasodilating prostanoids.
Exogenous growth hormone (GH) and insulin-like growth factor (IGF)-I induce an increase of renal hemodynamics in normal subjects, but the precise mechanism mediating this phenomenon has not been explored in humans. We investigated whether the renal response to exogenous GH requires the presence of vasodilating prostaglandins (PG). In 10 healthy normotensive women with normal renal function, the effect of recombinant human (rh)GH on glomerular filtration rate (GFR) was examined using an intraindividual cross-over design. The subjects were studied under conditions of normal hydration and controlled sodium and protein intake without and with coadministration of indomethacin, 150 mg/d. rhGH, 4.5 IU twice per day, was administered by subcutaneous self-injection for 3 days. GFR was measured as inulin clearance (Cin) in the morning hours in the fasting state in supine position before and after 3 days of rhGH treatment. Baseline GFR was 115.7 +/- 10.1 (SD) mL/min/1.73 m2. Three days of treatment with rhGH caused a 50% increase in serum IGF-I values and GFR increased by 10% to 127.9 +/- 11.7 mL/min/1.73 m2 (P < 0.03). The study was repeated under coadministration of indomethacin, which was started 2 days before application of rhGH. Despite a similar increase in serum IGF-I values, the increase in GFR was completely blocked by indomethacin. Urinary PGE2 excretion was not stimulated by rhGH, but decreased by 50% during indomethacin treatment, as expected. These findings suggest that the increase of GFR during GH treatment in humans is mediated by or requires the presence of vasodilating prostanoids.
Tönshoff
B
B
Department of Pediatrics, University of Heidelberg, Germany.
Nowack
R
R
Kurilenko
S
S
Blum
W F
WF
Seyberth
H W
HW
Mehls
O
O
Ritz
E
E
D000328:Adult; D015232:Dinoprostone / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D013006:Growth Hormone / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D011453:Prostaglandins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015232:Dinoprostone; D007213:Indomethacin