Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men.
Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1-5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline (DPD) cross-links in 53 women and 71 men aged 65-88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 (P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 (P = 0.0001). In women, IGFBP-1 was inversely related to insulin (P < 0.0005) and glucose (P < 0.005) and IGFBP-4 to osteocalcin (P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men (P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration (P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men (P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH (P < 0.05) and 56% after GH + testosterone (P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additionally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined.
Münzer
Thomas
T
Endocrine Section, Laboratory of Clinical Investigations, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Rosen
Clifford J
CJ
Harman
S Mitchell
SM
Pabst
Katherine M
KM
St Clair
Carol
C
Sorkin
John D
JD
Blackman
Marc R
MR
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015675:Osteocalcin / Q000097:blood; D013739:Testosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D001786:Blood Glucose; D012739:Gonadal Steroid Hormones; C032231:IGFBP1 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D015675:Osteocalcin; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C004648:testosterone enanthate; D017258:Medroxyprogesterone Acetate