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

V. Sibilia, D. Cocchi, I. Villa, N. Lattuada, A. Soglian, A. Rubinacci, E. E. Muller, A. Pecile, C. Netti

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. Methods: HEXA was administered for 60 days (50 μg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. Results: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5%) and bone area (+4.1%) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+ 7.2%) and bone area (+ 5.3%) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. Conclusions: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.

Original languageEnglish
Pages (from-to)855-862
Number of pages8
JournalEuropean Journal of Endocrinology
Volume146
Issue number6
Publication statusPublished - 2002

Fingerprint

Estrogens
Bone and Bones
Peptides
Bone Density
Diaphyses
Lumbar Vertebrae
Thigh
Alkaline Phosphatase
Serum
Insulin-Like Growth Factor I
hexarelin
Bone Remodeling
Photon Absorptiometry
deoxypyridinoline

ASJC Scopus subject areas

  • Endocrinology

Cite this

Bone effects of hexarelin, a GH-releasing peptide, in female rats : Influence of estrogen milieu. / Sibilia, V.; Cocchi, D.; Villa, I.; Lattuada, N.; Soglian, A.; Rubinacci, A.; Muller, E. E.; Pecile, A.; Netti, C.

In: European Journal of Endocrinology, Vol. 146, No. 6, 2002, p. 855-862.

Research output: Contribution to journalArticle

Sibilia, V, Cocchi, D, Villa, I, Lattuada, N, Soglian, A, Rubinacci, A, Muller, EE, Pecile, A & Netti, C 2002, 'Bone effects of hexarelin, a GH-releasing peptide, in female rats: Influence of estrogen milieu', European Journal of Endocrinology, vol. 146, no. 6, pp. 855-862.
Sibilia, V. ; Cocchi, D. ; Villa, I. ; Lattuada, N. ; Soglian, A. ; Rubinacci, A. ; Muller, E. E. ; Pecile, A. ; Netti, C. / Bone effects of hexarelin, a GH-releasing peptide, in female rats : Influence of estrogen milieu. In: European Journal of Endocrinology. 2002 ; Vol. 146, No. 6. pp. 855-862.
@article{9b6a0a8dba534867b3a05da26fb16c4f,
title = "Bone effects of hexarelin, a GH-releasing peptide, in female rats: Influence of estrogen milieu",
abstract = "Objective: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. Methods: HEXA was administered for 60 days (50 μg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. Results: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5{\%}) and bone area (+4.1{\%}) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+ 7.2{\%}) and bone area (+ 5.3{\%}) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. Conclusions: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.",
author = "V. Sibilia and D. Cocchi and I. Villa and N. Lattuada and A. Soglian and A. Rubinacci and Muller, {E. E.} and A. Pecile and C. Netti",
year = "2002",
language = "English",
volume = "146",
pages = "855--862",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "6",

}

TY - JOUR

T1 - Bone effects of hexarelin, a GH-releasing peptide, in female rats

T2 - Influence of estrogen milieu

AU - Sibilia, V.

AU - Cocchi, D.

AU - Villa, I.

AU - Lattuada, N.

AU - Soglian, A.

AU - Rubinacci, A.

AU - Muller, E. E.

AU - Pecile, A.

AU - Netti, C.

PY - 2002

Y1 - 2002

N2 - Objective: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. Methods: HEXA was administered for 60 days (50 μg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. Results: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5%) and bone area (+4.1%) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+ 7.2%) and bone area (+ 5.3%) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. Conclusions: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.

AB - Objective: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. Methods: HEXA was administered for 60 days (50 μg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. Results: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5%) and bone area (+4.1%) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+ 7.2%) and bone area (+ 5.3%) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. Conclusions: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.

UR - http://www.scopus.com/inward/record.url?scp=0036306249&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036306249&partnerID=8YFLogxK

M3 - Article

C2 - 12039707

AN - SCOPUS:0036306249

VL - 146

SP - 855

EP - 862

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 6

ER -