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Suppression of growth hormone release restores phosphaturic response to PTH in immature rats
S E Mulroney1, M D Lumpkin, A Haramati
1Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, District of Columbia 20007.
Insights
Growth hormone (GH) suppression enhances the kidney's phosphate excretion response to parathyroid hormone (PTH) in immature rats. This suggests GH normally blunts the renal phosphaturic effect of PTH during growth.
Area of Science:
- Nephrology
- Endocrinology
- Pediatric Physiology
Background:
- Immature rats show a reduced urinary phosphate excretion response to parathyroid hormone (PTH).
- Growth hormone (GH) promotes renal phosphate retention in young animals, potentially interfering with PTH's effects.
- GH's role in modulating the renal response to PTH in growing animals requires further investigation.
Purpose of the Study:
- To determine if suppressing growth hormone (GH) release affects the renal phosphate excretion response to PTH in immature rats.
Main Methods:
- Immature rats were treated with a GH-releasing factor antagonist ([N-acetyl-Tyr1-D-Arg2]-GRF-(1-29)-NH2 or GRF-AN).
- Rats underwent thyroparathyroidectomy before receiving increasing doses of PTH.
- Fractional excretion of phosphate (FEPi) was measured to assess renal response.
Main Results:
- Immature rats exhibited a blunted phosphaturic response to PTH compared to adult rats.
- GRF-AN treatment in immature rats enhanced the phosphaturic response to PTH.
- The enhanced response in GRF-AN treated immature rats was comparable to that of adult rats.
Conclusions:
- Suppression of GH release by GRF-AN normalizes the renal phosphate excretion response to PTH in immature rats.
- GH normally attenuates the phosphaturic effect of PTH in growing animals.
- This finding has implications for understanding phosphate homeostasis during growth.
Abstract:
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)