The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats

Abstract

Growth hormone (GH) is of importance for normal bone remodelling. A recent clinical study demonstrated that MK-677, a member of a class of GH secretagogues (GHSs), increases serum concentrations of biochemical markers of bone formation and bone resorption. The aim of the present study was to investigate whether the GHSs, ipamorelin (IPA) and GH-releasing peptide-6 (GHRP-6), increase bone mineral content (BMC) in young adult female rats. Thirteen-week-old female Sprague-Dawley rats were given IPA (0·5 mg/kg per day; n=7), GHRP-6 (0·5 mg/kg per day; n=8), GH (3·5 mg/kg per day; n=7), or vehicle administered continuously s.c. via osmotic minipumps for 12 weeks. The animals were followed in vivo by dual X-ray absorptiometry (DXA) measurements every 4th week. After the animals were killed, femurs were analysed in vitro by mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. After this, excised femurs and vertebrae L6 were analysed by the use of Archimedes' principle and by determinations of ash weights. All treatments increased body weight and total tibial and vertebral BMC measured by DXA in vivo compared with vehicle-treated controls. However, total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected. Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged. The pQCT measurements in vitro revealed that the increase in the cortical BMC was due to an increased cross-sectional bone area, whereas the cortical volumetric BMD was unchanged. Femur and vertebra L6 volumes were increased but no effect was seen on the volumetric BMDs as measured by Archimedes' principle. Ash weight was increased by all treatments, but the mineral concentration was unchanged. We conclude that treatment of adult female rats with the GHSs ipamorelin and GHRP-6 increases BMC as measured by DXA in vivo. The results of in vitro measurements using pQCT and Archimedes' principle, in addition to ash weight determinations, show that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.

Glucocorticoid-dependent stimulation of adiposity and appetite by a ghrelin mimetic in the rat

“…The mismatch between the GHS effects on body weight gain and fat accumulation in these ADX rats provides an indication that there is a fat-free component to the weight gain induced by GHS. This could reflect a GH-dependent stimulatory effect on bone and/or lean body mass (25). In the present study, the acute effects of GHRP-6 on food intake were observed in adrenal-intact rats, and this orexigenic effect was significant up to 7 h following a single peripheral injection administered during the morning, a time when the animals are normally satiated.…”

Bone effects of hexarelin, a GH-releasing peptide, in female rats: influence of estrogen milieu

“…In keeping with this finding, long-term administration of ipamorelin and GHRP-6, two other GHSs, induced an increment of lumbar BMC in young intact female rats (15).…”

A novel GH secretagogue, A233, exhibits enhanced growth activity and innate immune system stimulation in teleosts fish

“…In adult rats, GHRP6 also increased body weight (Svensson et al 2000) as well as other GHSR agonists, like SM-130686 administered orally (Nagamine et al 2001) and BIM-28131 administered by s.c. injection (Strassburg et al 2008). It has been recently reported that GHSR1a agonist, a pentapeptide with D-amino acids, promotes weight gain in rats, by i.p.…”