Antagonist to GH-releasing factor inhibits growth and renal Pi reabsorption in immature rats.
Compared with adult rats, the immature rat has an enhanced tubular capacity for phosphate reabsorption, which presumably facilitates the growth process. Since the main driving force for growth is thought to be the pulsatile release of growth hormone, we examined the possibility that the adaptation in phosphate handling by the immature kidney is promoted by growth hormone (GH). To address this issue, we used a synthetic peptide antagonist to GH-releasing factor (GRF-AN) that we have shown blocks episodic GH secretion, and attenuates somatic growth. Immature male Wistar rats (4-5 wk of age) were catheterized with Silastic jugular cannulas and placed in metabolic cages. The rats were injected intravenously with either saline or GRF-AN (100 micrograms/kg) twice daily for 4 days. On the 4th day, they were prepared for renal clearance experiments to assess the maximum capacity for phosphate transport (TmPi). In animals treated with GRF-AN, there was an attenuated gain in body weight over 4 days of treatment (5 +/- 2 vs. 23 +/- 2% in saline controls, P less than 0.01). The suppressed growth was associated with a doubling of daily urinary phosphate excretion, and a reduction in the TmPi (3.3 +/- 0.1 vs. 4.6 +/- 0.3 mumol/ml in controls, P less than 0.01). A single injection of the antagonist to a separate group of immature rats did not alter TmPi. Thus injections of this new antagonist to GH-releasing factor over a 4-day period inhibit the pulsatile release of GH and significantly attenuate growth. The decline in growth of the immature rat was associated with a decrease in the renal capacity for phosphate reabsorption, down to levels seen in normal adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Mulroney
S E
SE
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007.
Lumpkin
M D
MD
Haramati
A
A
D000042:Absorption; D000818:Animals; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone