Regulation of plasma growth hormone-binding proteins in health and disease

Baumann, Gerhard; Shaw, Melissa A.; Amburn, Klaus

doi:10.1016/0026-0495(89)90108-x

Cited by 156 publications

(67 citation statements)

References 13 publications

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“…In contrast, B max values did change throughout pouch life with binding capacity increasing from non-detectable levels (25-38 days post-partum) to about half that observed in the adult possum by around 117 days post-partum. An increase in GHBP levels with age, like that seen in the possum, is also evident in the human, rat and pig (Daughaday et al 1987, Baumann et al 1989, Mulumba et al 1991, Ambler et al 1992. In the human, GHBP levels increase from low levels in the fetus and neonate to reach peak levels between 20 and 46 years of age and thereafter decline (Daughaday et al 1987).…”

Section: Discussionmentioning

confidence: 89%

Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

Saunders

Gemmell²,

Waters³

et al. 2002

Journal of Endocrinology

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Plasma concentrations of growth hormone (GH) were measured in the brushtail possum (Trichosurus vulpecula) pouch young from 25 through to 198 days post-partum (n=71). GH concentrations were highest early in pouch life (around 100 ng/ml), and thereafter declined in an exponential fashion to reach adult concentrations (10·8 1·8 ng/ml; n=21) by approximately 121-145 days post-partum, one to two months before the young is weaned. Growth hormone-binding protein (GHBP), which has been shown to modify the cellular actions of GH in eutherian mammals, was identified for the first time in a marsupial. Based on size exclusion gel filtration, possum GHBP had an estimated molecular mass of ]65 kDa, similar to that identified in other mammalian species, and binding of 125 I-labelled human GH (hGH) was displaced by excess hGH (20 µg). An immunoprecipitation method, in which plasma GHBP was rendered polyethylene glycol precipitable with a monoclonal antibody to the rabbit GHBP/GH receptor (MAb 43) and labelled with 125 I-hGH, was used to quantitate plasma GHBP by Scatchard analysis in the developing (pooled plasma samples) and adult (individual animals) possums. Binding affinity (K a ) values in pouch young aged between 45 and 54 and 144 and 153 days post-partum varied between 1·0 and 2·4 10 9 /M, which was slightly higher than that in adult plasma (0·96 0·2 10 9 /M, n=6). Binding capacity (B max ) values increased from nondetectable levels in animals aged 25-38 days post-partum to reach concentrations around half that seen in the adult (1·4 0·2 10 -9 M) by about 117 days post-partum and remained at this level until 153 days post-partum. Therefore, in early pouch life when plasma GH concentrations are highest, the very low concentrations of GHBP are unlikely to be important in terms of competing with GH-receptor for ligand or altering the half-life of circulating GH.

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Section: Discussionmentioning

confidence: 89%

Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

Saunders

Gemmell²,

Waters³

et al. 2002

Journal of Endocrinology

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“…Moreover, the r-hGH-induced increase of plasma GH-BP activity during long-term administration was transient, as indicated by the dropoff observed at $360 d (Table 2). That unexpected event may be due to the failure of the long-term exposure to supraphysiologic doses of the hormone to sustain the up-regulation of the hGH receptor; a similar mechanism seems involved in patients with acromegaly (29), in whom elevated GH levels and low GH-BP activity coexist, suggesting a down-regulation of the GH receptor due to the long-lasting high GH levels (27). Others did not observe significant variations of plasma GH-BP activity in long-term r-hGH-treated Turner patients (20); it should be noted that the study involved adolescent girls in whom, due to overweight (29,30), the baseline levels of GH-BP were higher than those found in either bone age-or chronologic age-matched controls.…”

Section: Discussionmentioning

confidence: 99%

Plasma Growth Hormone-Binding Protein Activity, Insulin-like Growth Factor I, and Its Binding Protein Levels in Patients with Turner's Syndrome: Effect of Short- and Long-Term Recombinant Human Growth Hormone Administration

1995

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Plasma growth hormone-binding protein (GH-BP) activity and the levels of IGF-I and its binding proteins (IGFBP) were studied in eight girls with Turner's syndrome before and during recombinanthGH (r-hGH) administration. Growth hormone and GH-BP activity were assayed at baseline and hourly, over a 12-h period, after an intramuscular bolus of 0.09 mgikg of the hormone. After 7 d, each patient received r-hGH at 0.33 mgikg/weekly s.c. every day at nighttime; plasma growth hormone-binding protein activity, blood IGF-I, and IGFBP were evaluated before and on d 7, 30, 180, and 360. Baseline reference values were obtained from 10 bone agematched healthy girls. Basal GH-BP activity, IGF-I, and IGFBP levels were similar in patients and controls. Four h after the intramuscular injection, GH-BP activity maximally increased and returned to baseline 6-7 h later; during long-term r-hGH administration GH-BP activity peaked at + 180 d but declined to pretreatment at +360 d. IGF-I, IGFBP-3, and IGFBP-4 increased under r-hGH and, in contrast to GH-BP activity, remained high throughout the study. In conclusion, in girls with Turner's syndrome, GH-BP activity, IGF-I, IGFBP-3, and IGFBP-4 are induced by r-hGH. However, the increase of IGF-I and IGFBP-3 does not require an increased level of the cellular growth hormone receptors, as suggested by the unchanged +360 d values of plasma GH-BP activity compared with baseline. The absence of an association among any of the biochemical parameters studied and the growth of the patients taking r-hGH suggests that a peripheral defect may affect their growth. (Pediatr Res 37: 106111, 1995)

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“…GHBP Assay-GHBP activity was measured in conditioned media by a standard GH binding assay, as previously reported (11,12,28). Conditioned medium (0.05 or 0.4 ml, as indicated) from cells treated as indicated was incubated with freshly labeled 125 I-hGH (ϳ0.5 ng) for 45 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Metalloprotease-mediated GH Receptor Proteolysis and GHBP Shedding

Wang¹,

He²,

Gerhart³

et al. 2002

Journal of Biological Chemistry

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Growth hormone-binding protein (GHBP) is complexed to a substantial fraction of circulating GH. In humans, rabbits, and other species, GHBP derives from proteolytic shedding of the GH receptor (GHR) extracellular domain. In cell culture studies, stimuli such as phorbol ester, platelet-derived growth factor, or serum induce GHR proteolysis, which concomitantly yields shed GHBP in cell supernatants and a cell-associated cytoplasmic domain-containing GHR remnant. This process is sensitive to metalloprotease inhibition, and genetic reconstitution studies identify tumor necrosis factor-␣ converting enzyme (TACE/ADAM-17), a transmembrane metalloprotease, as a GHR sheddase. Stimuli that induce GHR proteolysis render cells less responsive to GH, but the mechanism(s) of this desensitization is not yet understood. In this study, we mapped the rabbit (rb) GHR cleavage site. We adenovirally expressed a C-terminal epitope-tagged rbGHR lacking most of its cytoplasmic domain, purified the remnant protein induced by the phorbol ester, PMA, and derived the cleavage site by N-terminal sequencing of the purified remnant. The N-terminal sequence, 239 FTCEEDFR 246 , matched perfectly the rbGHR and suggests that cleavage occurs eight residues from the membrane in the proximal extracellular domain stem region. Deletion and alanine substitution mutagenesis indicated that, similar to other TACE substrates, the spacing of residues in this region, more than their identity, influences GHR cleavage susceptibility. Further, we determined that PMA pretreatment desensitized a cleavage-sensitive GHR mutant, but not a cleavage-insensitive mutant, to GH-induced JAK2 activation. These results suggest that inducible GHR proteolysis can regulate GH signaling.

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Regulation of plasma growth hormone-binding proteins in health and disease

Cited by 156 publications

References 13 publications

Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

Plasma Growth Hormone-Binding Protein Activity, Insulin-like Growth Factor I, and Its Binding Protein Levels in Patients with Turner's Syndrome: Effect of Short- and Long-Term Recombinant Human Growth Hormone Administration

Metalloprotease-mediated GH Receptor Proteolysis and GHBP Shedding

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