Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men

Abstract

. Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men. Am J Physiol Endocrinol Metab 290: E1006 -E1013, 2006. First published January 3, 2006 doi:10.1152/ajpendo.00166.2005.-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 ϩ 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 Ͻ 0.001 and P Ͻ 0.0001) and IGFBP-1 to IGFBP-2 (P ϭ 0.0001). In women, IGFBP-1 was inversely related to insulin (P Ͻ 0.0005) and glucose (P Ͻ 0.005) and IGFBP-4 to osteocalcin (P Ͻ 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 Ͻ 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration (P Ͻ 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH ϩ sex steroids, whereas GH decreased IGFBP-2 by 15% in men (P Ͻ 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH (P Ͻ 0.05) and 56% after GH ϩ testosterone (P ϭ 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additonally, 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. growth hormone; insulin-like growth factor-binding protein INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS (IGFBPs) are members of a structurally and genetically related superfamily of proteins that bind to insulin-like growth factors (IGFs) with high, but variable, affinities (34). In addition to their principal roles as modulators of endocrine, paracrine, and autocrine actions of IGFs, IGFBPs exert growth hormone (GH)-independent effects on various tissues in vivo and in vitro (38, 59). The detailed mechanisms of IGFBP synthesis and their metabolic activities remain incompletely understood. However, it has been reported (6, 64, 65) that circulating levels of IGFBP-1 are regulated by insulin and IGF-I. IGFBP-2 is also related to insulin levels (13), whereas increases in IGFBP-3 are closely correlated with those in IGF-I in response to GH in children (47) and adults (39) with GH deficiency (GHD). IGFBP-4 and -5 inhibit and stimulate, respectively, IGF-mediated effects on bone (53). How these important modulatory proteins are affected by aging and age-related changes in endocrine balance and the extent to which hormone replacement reverses such changes is incomplet...

Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month’s treatment with supraphysiological doses of growth hormone

“…This finding is largely in accordance with previous clinical studies of healthy subjects and of GHD patients on GH treatment, demonstrating that IGFBP-4 and IGFBP-5 levels are influenced by the GH/IGF-I axis [21,22,32,33].…”

“…In a study on healthy, aged women and men, IGFBP-4 levels were unaffected after 26 weeks of GH treatment, whereas IGFBP-5 increased by 20% in men after GH. The weekly GH dose in that study was, however, approximately only one-sixth of the dose per kg and week used in our study [32].…”

Differing levels of testosterone and the prostate: a physiological interplay

“…Munzer et al 54 demonstrated that hormone administration increased IGFBP3 and IGFBP5 levels. IGFBP3 is the most abundant circulating IGF-binding protein that inhibits cell growth and induces apoptosis by both IGF-I-dependent and IGF-I-independent pathways in many cancers, including prostate cancer.…”

“…[52][53][54][55][56] Animal experiments demonstrate that tumor growth can be inhibited by disrupting IGF-I signaling pathways 53 and in a nested case-control study using data derived from the Physicians' Health Study cohort it was demon strated that increasing plasma levels of IGF-I were directly linked to increasing prostate cancer risk. 52 After adjusting for IGF-binding proteins (such as IGFBP3), men with a serum PSA level >4 ng/ml in combination with the highest quartile of IGF-I had a 17.5-fold risk of prostate cancer.…”

Effects of long-term continuous positive airway pressure on body composition and IGF1

“…Taken together, these data suggest that in addition to normal aging, sleep disturbances such as sleep apnea may substantially affect GH secretion and action, and thereby, have additional impact on the potential effects of CPAP treatment. Several studies have reported a sexual dimorphic interaction of GH axis activation with sleep (22)(23)(24), and both GH administration to healthy old persons (25,26) and GH therapy in patients with adult GHD syndrome (27) revealed that changes in LBM or adipose tissue depended on sex.…”