Suppression of growth hormone release restores phosphaturic response to PTH in immature rats
Mulroney, S.E.; Lumpkin, M.D.; Haramati, A.
American Journal of Physiology 261(6 Pt 2): F1110-F1113
1991
ISSN/ISBN: 0002-9513 PMID: 1661083 Document Number: 385174
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 .mu.g.cntdot.100 g-1.cntdot.h-1) in the acutely thyroparathyroidectomized immature rat. Baseline fractional excretion of phosphate (FEPi), before administration of PTH, was negligible in all groups (< 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. 21.2 .+-. 3.5 to 31.9 .+-. 4.4% in adult rats, P < 0.05). In contrast, immature rats treated for 2 days with GRF-AN (100 .mu.g/mkg, twice daily) displayed an enhanced phosphaturic response to (FEPi from 12.0 .+-. 4.2 to 42.9 .+-. 3.7%, P < 0.05) compared with immature control rats, which was not different from that observed in control adult rats. Urinary cAMP excretion increased progressively, but the response did not differ between the groups at any dose. Thus the immature rat is capable of a full renal response to PTH, but the phosphaturic effect of PTH may be attenuated normally in the developing animal by the phosphate-conserving actions of GH.