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Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans.
J Clin Endocrinol Metab. 1996 Jun; 81(6):2222-6.JC

Abstract

Sex steroids, GH, and insulin-like growth factor I (IGF-I) have all been shown to be highly anabolic in bone. Using available markers of bone formation, we measured the changes in serum concentrations of carboxy-terminal propeptide of type I collagen (PICP) and osteocalcin in five groups of subjects given different bone anabolic hormones: group I (five males and three females; mean +/- SE age, 25 +/- 2 yr) received recombinant human IGF-I (rhIGF-I) as a constant 28-h infusion i.v. (5-10 micrograms/kg.h); group II (three males and two females; 25 +/- 2 yr) received rhIGF-I (100 micrograms/kg, sc, twice daily) for 5-7 days; group III (five males; 28 +/- 2 yr) received rhGH (0.025 mg/kg.day, sc, for 7 days, alone (group IIIa) or followed by a 28-h sc infusion of rhIGF-I (10 micrograms/kg.h) in addition to rhGH (group IIIb); group IV (six prepubertal boys; 13 +/- 0.6 yr) received testosterone enanthate (100 mg, im) twice over 4 weeks; and group V (five hypogonadal girls with Turner's syndrome) received different forms of estrogen for 4 weeks. Most groups (except for III) had deoxypyridinoline concentrations (a marker of bone resorption) measured in urine as well. Each subject served as his/her own control. rhIGF-I treated subjects in group I showed a marked decrease in circulating PICP concentrations after 4 h of infusion (from 116.8 +/- 19.2 micrograms/L to 89.6 +/- 16.3; P < 0.01), followed by a marked increase at 28 h (137.6 +/- 19.7; P < 0.01) and a sustained increase 5-7 days after sc therapy (group II). This decrease followed by an increase in PICP concentrations after rhIGF-I may be secondary to the marked suppression of circulating insulin observed at 4 h followed by the establishment of an insulin-like effect of the peptide. Subjects receiving rhGH alone (group IIIa) also had comparable increases in circulating PICP (from 107.6 +/- 8.7 to 125.0 +/- 10.9; P < 0.01) and a further additive increase when rhIGF-I was coadministered (140.9 +/- 10.3; P < 0.01). These changes were accompanied by comparable increases in IGF-I concentrations in all groups (I, II, and III). Hypogonadal children had higher levels of circulating PICP than adults and showed the most significant increases after therapy [group IV, 212.2 +/- 13.8 to 429.9 +/- 52.4 micrograms/L (P < 0.001); group V, 312.8 +/- 49.0 to 355.5 +/- 44.3 (P < 0.04)]. The latter was observed despite either a modest (group IV) or no increase (group V) in circulating IGF-I concentrations. None of the groups studied showed any change in serum osteocalcin concentrations after treatment. Urinary deoxypridinoline concentrations also increased after rhIGF-I and testosterone administration. We conclude that rhIGF-I, rhGH, and sex steroid hormones all markedly increase measures of bone turnover, and that rhIGF-I and rhGH can synergize on this effect on bone. These data collectively suggest that IGF-I and sex steroid hormones (testosterone and estrogen) can impact bone formation independently, and that the actions of IGF-I, GH, sex steroid hormones (and perhaps insulin) may synergize to maximally stimulate attainment of peak bone mass in humans. PICP measurement appears to be a sensitive marker of short term anabolic hormone actions in bone.

Authors+Show Affiliations

Nemours Children's Clinic, Jacksonville, Florida 32207, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8964855

Citation

Mauras, N, et al. "Recombinant Human Insulin-like Growth Factor I, Recombinant Human Growth Hormone, and Sex Steroids: Effects On Markers of Bone Turnover in Humans." The Journal of Clinical Endocrinology and Metabolism, vol. 81, no. 6, 1996, pp. 2222-6.
Mauras N, Doi SQ, Shapiro JR. Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans. J Clin Endocrinol Metab. 1996;81(6):2222-6.
Mauras, N., Doi, S. Q., & Shapiro, J. R. (1996). Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans. The Journal of Clinical Endocrinology and Metabolism, 81(6), 2222-6.
Mauras N, Doi SQ, Shapiro JR. Recombinant Human Insulin-like Growth Factor I, Recombinant Human Growth Hormone, and Sex Steroids: Effects On Markers of Bone Turnover in Humans. J Clin Endocrinol Metab. 1996;81(6):2222-6. PubMed PMID: 8964855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans. AU - Mauras,N, AU - Doi,S Q, AU - Shapiro,J R, PY - 1996/6/1/pubmed PY - 1996/6/1/medline PY - 1996/6/1/entrez SP - 2222 EP - 6 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 81 IS - 6 N2 - Sex steroids, GH, and insulin-like growth factor I (IGF-I) have all been shown to be highly anabolic in bone. Using available markers of bone formation, we measured the changes in serum concentrations of carboxy-terminal propeptide of type I collagen (PICP) and osteocalcin in five groups of subjects given different bone anabolic hormones: group I (five males and three females; mean +/- SE age, 25 +/- 2 yr) received recombinant human IGF-I (rhIGF-I) as a constant 28-h infusion i.v. (5-10 micrograms/kg.h); group II (three males and two females; 25 +/- 2 yr) received rhIGF-I (100 micrograms/kg, sc, twice daily) for 5-7 days; group III (five males; 28 +/- 2 yr) received rhGH (0.025 mg/kg.day, sc, for 7 days, alone (group IIIa) or followed by a 28-h sc infusion of rhIGF-I (10 micrograms/kg.h) in addition to rhGH (group IIIb); group IV (six prepubertal boys; 13 +/- 0.6 yr) received testosterone enanthate (100 mg, im) twice over 4 weeks; and group V (five hypogonadal girls with Turner's syndrome) received different forms of estrogen for 4 weeks. Most groups (except for III) had deoxypyridinoline concentrations (a marker of bone resorption) measured in urine as well. Each subject served as his/her own control. rhIGF-I treated subjects in group I showed a marked decrease in circulating PICP concentrations after 4 h of infusion (from 116.8 +/- 19.2 micrograms/L to 89.6 +/- 16.3; P < 0.01), followed by a marked increase at 28 h (137.6 +/- 19.7; P < 0.01) and a sustained increase 5-7 days after sc therapy (group II). This decrease followed by an increase in PICP concentrations after rhIGF-I may be secondary to the marked suppression of circulating insulin observed at 4 h followed by the establishment of an insulin-like effect of the peptide. Subjects receiving rhGH alone (group IIIa) also had comparable increases in circulating PICP (from 107.6 +/- 8.7 to 125.0 +/- 10.9; P < 0.01) and a further additive increase when rhIGF-I was coadministered (140.9 +/- 10.3; P < 0.01). These changes were accompanied by comparable increases in IGF-I concentrations in all groups (I, II, and III). Hypogonadal children had higher levels of circulating PICP than adults and showed the most significant increases after therapy [group IV, 212.2 +/- 13.8 to 429.9 +/- 52.4 micrograms/L (P < 0.001); group V, 312.8 +/- 49.0 to 355.5 +/- 44.3 (P < 0.04)]. The latter was observed despite either a modest (group IV) or no increase (group V) in circulating IGF-I concentrations. None of the groups studied showed any change in serum osteocalcin concentrations after treatment. Urinary deoxypridinoline concentrations also increased after rhIGF-I and testosterone administration. We conclude that rhIGF-I, rhGH, and sex steroid hormones all markedly increase measures of bone turnover, and that rhIGF-I and rhGH can synergize on this effect on bone. These data collectively suggest that IGF-I and sex steroid hormones (testosterone and estrogen) can impact bone formation independently, and that the actions of IGF-I, GH, sex steroid hormones (and perhaps insulin) may synergize to maximally stimulate attainment of peak bone mass in humans. PICP measurement appears to be a sensitive marker of short term anabolic hormone actions in bone. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/8964855/Recombinant_human_insulin_like_growth_factor_I_recombinant_human_growth_hormone_and_sex_steroids:_effects_on_markers_of_bone_turnover_in_humans_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.81.6.8964855 DB - PRIME DP - Unbound Medicine ER -