Suppression of growth hormone release restores phosphaturic response to PTH in immature rats.
Immature rats display a blunted rise in urinary phosphate but not adenosine 3',5'-cyclic monophosphate (cAMP) excretion in response to parathyroid hormone (PTH), perhaps as a consequence of the increased demand for phosphate during growth. Because a major driving force for growth is growth hormone (GH), and in view of the fact that GH has been shown to promote renal phosphate retention in the immature animal, it is possible that GH may attenuate the phosphaturic effect of PTH. The objective of this study was to determine whether suppression of pulsatile GH release, during administration of a synthetic peptide antagonist to GH-releasing factor, i.e., [N-acetyl-Tyr1-D-Arg2]-GRF-(1-29)-NH2 (GRF-AN), alters the renal response to increasing doses of PTH (1.5-15.0 micrograms.100 g-1.h-1) in the acutely thyroparathyroidectomized immature rat. Baseline fractional excretion of phosphate (FEPi), before administration of PTH, was negligible in all groups (less than 0.05%). Infusion of PTH resulted in an attenuated rise in FEPi in immature control rats compared with adult control rats (from 3.8 +/- 1.4% at lowest PTH dose to 16.7 +/- 3.1% at highest dose in immature rats vs. 21.1 +/- 3.5 to 31.9 +/- 4.4% in adult rats, P less than 0.05). In contrast, immature rats treated for 2 days with GRF-AN (100 micrograms/kg, twice daily) displayed an enhanced phosphaturic response (FEPi from 12.0 +/- 4.2 to 42.9 +/- 3.7%, P less than 0.05) compared with immature control rats, which was not different from that observed in control adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Mulroney
S E
SE
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, District of Columbia 20007.
Lumpkin
M D
MD
Haramati
A
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000652:urine; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010710:Phosphates / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D017337:Sermorelin / Q000031:analogs & derivatives*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C058677:somatotropin releasing hormone (1-29)amide, N-acetyl-tyrosyl(1)-arginyl(2)-; D000242:Cyclic AMP