Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.
Aagaard. Niels Kristian NK; Grøfte. Thorbjørn T; Greisen. Jacob J; Malmlöf. Kjell K; Johansen. Peter B PB; Grønbaek. Henning H; Ørskov. Hans H; Tygstrup. Niels N; Vilstrup. Hendrik H
Key Findings
- Prednisolone (a steroid) dramatically increased liver urea production and caused a negative nitrogen balance, indicating catabolism.
- Co‑administering growth hormone cut liver urea synthesis by about one‑third and restored nitrogen balance.
- Ipamorelin reduced liver urea synthesis by ~20%, lowered urea‑cycle gene expression, and neutralized the negative nitrogen balance, though less potently than growth hormone.
Practical Outcomes
- For steroid‑using biohackers, ipamorelin may help blunt the muscle‑wasting side effects of high‑dose steroids by improving nitrogen retention. The animal data suggest a modest benefit, so if you experiment, start with low doses and monitor protein retention markers. Human studies are lacking, so treat this as a hypothesis‑generating insight rather than a proven protocol.
Summary
In rats given a high dose of the steroid prednisolone, the peptide ipamorelin (a growth‑hormone‑releasing drug) helped keep the body from losing as much nitrogen, which is a sign of reduced muscle‑breakdown. It did this by lowering the liver’s urea‑making activity and improving overall nitrogen balance, though it wasn’t quite as strong as giving growth hormone itself.
Abstract
Growth hormone (GH) reduces the catabolic side effects of steroid treatment via effects on the amino-nitrogen metabolism. Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on selected hepatic measures of alpha-amino-nitrogen conversion during steroid-induced catabolism. Five groups of rats were included: (1) free-fed controls (2) pair-fed controls (3) prednisolone (delcortol, 4 mg x kg(-1) x day(-1)) (4) prednisolone and GH (1 mg x kg(-1) x day(-1)) (5) prednisolone and Ipamorelin (0.5 mg x kg(-1) x day(-1)). After seven days the hepatic capacity of urea-N synthesis (CUNS) was determined in parallel with measurements of liver mRNA levels of urea cycle enzymes, whole-body N-balance, and N-contents of various organs. Compared to pair-fed controls, prednisolone increased CUNS (p<0.01) as well as the expression of urea cycle genes (p<0.01), and decreased N-balance (p<0.01) as well as organ N-contents (p<0.05). Compared to prednisolone treated animals, co-administration of GH reduced CUNS by 33% (p<0.01), normalized urea cycle gene expression, improved N-balance 2.5-fold, and normalized or improved organ N-contents. In prednisolone treated rats Ipamorelin reduced CUNS by 20% (p<0.05), decreased the expression of urea cycle enzymes, neutralised N-balance, and normalized or improved organ N-contents. Accelerated nitrogen wasting in the liver and other organs caused by prednisolone treatment was counteracted by treatment with either GH or its secretagogue Ipamorelin, though at the doses given less efficiently by the latter. This functional study of animals confirms that the GH secretagogue exerts GH related metabolic effects and may be useful in the treatment of steroid-induced catabolism.
Study Information
pubmed
2009
2009-02-23T00:00:00.000Z
10.1016/j.ghir.2009.01.001
4
38