Investigating the role of the growth hormone-insulin-like growth factor (GH-IGF) axis as a determinant of male bone mineral density (BMD)

INTRODUCTION: The GH-IGF axis has profound effects on bone metabolism and may be important in the etiology of idiopathic osteoporosis. Serum IGF-I is often low in men with osteoporosis, which may be attributable to GH hypo-secretion or hepatic GH insensitivity. We studied the GH-IGF axis in depth to look for evidence to support these hypotheses. MATERIALS AND METHODS: 28 healthy 60- to 70-year-old men with low, intermediate, or normal BMD were studied. GH secretion was measured by overnight urine collection. GH reserve was assessed by exercise and glucagon stimulation tests. Hepatic IGF-I production was investigated using a GH-IGF-I generation test. Data were analyzed using Pearson's correlation coefficient, linear regression, and analysis of variance. RESULTS: Serum IGF-I was reduced in subjects with low BMD (P = 0.009). There was no difference in GH secretion or reserve between the groups. Overall, GH reserve and IGF-I were positively related but this was attenuated in the low BMD group. However, no statistically significant difference in IGF-I generation capacity between BMD groups was found. CONCLUSIONS: Men with reduced BMD have low IGF-I but normal GH secretion and reserve. Our data suggested, but could not confirm, hepatic resistance to GH as a mechanism for this association.     

Provocative stimulation of growth hormone: a monozygotic twin study discordant for spinal cord injury

BACKGROUND/OBJECTIVE: A blunted growth hormone (GH) response to provocative testing and/or low levels of plasma insulin-like growth factor-I (IGF-I) have been reported in persons with spinal cord injury (SCI). A reduction in activity of the GH-IGF-I axis may have deleterious effects on body composition and function. Provocative testing for GH stimulation was performed to determine the response in monozygotic twins that were discordant for SCI. METHODS: GH stimulation testing was performed by the administration of intravenous arginine. RESULTS: Nine SCI twins with paraplegia, a mean age of 39 +/- 9 years, and duration of injury of 14 +/- 9 years were studied. The twins with SCI had a significantly lower body mass index than non-SCI twins (22.5 +/- 4.0 vs 25.1 +/- 4.2 kg/m2; P < 0.05); percent fat mass was greater in the twins with SCI (30 +/- 11% vs 22 +/- 10%; P < 0.05). Baseline serum GH was correlated with percent fat only in the SCI twins. The response to GH provocative stimulation was less in the twins with SCI: peak GH response was 5.8 +/- 6.6 vs 13.0 +/- 7.3 ng/mL (P < 0.05), and sum GH response was 15.7 +/- 15.6 vs 30.2 +/- 17.3 ng/mL (P = 0.06). Although baseline serum GH was correlated with stimulated response in the SCI twins, this relationship was not found in the non-SCI twins. Adiposity was positively related to the provocative serum GH response in twins with SCI rather than negatively related, as noted in the non-SCI twins. CONCLUSIONS: This study confirms and extends prior work that reported a reduction in stimulated GH release in persons with SCI, which was related to baseline values.     

Regulation of cartilage growth by growth hormone and insulin-like growth factor I

A number of studies have shown that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have important regulatory roles for skeletal growth. However, it has been a matter of controversy whether GH acts directly on cells in the growth plate or if the growth-promoting effects of GH are mediated by liver-derived (endocrine-acting) IGF-I. With the recognition that GH regulates the production of IGF-I in multiple extra-hepatic tissues, autocrine and paracrine functions of IGF-I have been suggested as important components of GH action. This review focuses on recent developments in our understanding of the cellular mechanisms by which GH promotes longitudinal bone growth and the inter-relationship between GH and IGF-I in the growth plate.     

Serum levels of bone GLA protein (osteocalcin,BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegly: Effects of long-term octreotide treatment

Summary We measured serum concentrations of bone Glaprotein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150–450 g/day for 6–33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2±4.2 g/liter versus 8.0±3.3 g/liter, P<0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r=0.67, P<0.001). Also IGF-I concentrations were positively correlated with BGP (r=0.66, P<0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146±46 g/liter versus 127±44 g/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.     

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.     

Growth hormone directly and indirectly stimulates articular chondrocyte cell growth

Although growth hormone (GH) is known to regulate cartilage growth and differentiation during development, it is still unclear whether the cell growth of articular chondrocytes is stimulated directly by GH or mediated by GH-induced insulin-like growth factor-I (IGF-I). In the present study, we focused on whether GH directly or indirectly stimulates articular chondrocyte proliferation. Monolayer articular chondrocytes from 5-week-old male Sprague-Dawley rats were cultured in Ham's F-12/Dulbecco's modified essential medium supplemented with 10% fetal bovine serum. Stimulation of DNA synthesis by GH was dose-dependent between 0.1 and 1 microg/ml, and the maximum active concentration of GH was 500 ng/ml, which induced a 3.5-fold increase over control values. Anti-IGF-I antiserum neutralized about 80% of GH-induced DNA synthesis. GH stimulated the secretion of IGF-I into the conditioned medium in a dose-responsive manner. To determine whether GH stimulated DNA synthesis directly, we investigated the time-course changes in mRNA expression of IGF-I and the proto-oncogene c-myc. Induction of IGF-I mRNA occurred at 4 h, and reached a maximum level at 12 h, whereas the expression of c-myc mRNA was induced within 4 h, and continued to increase until 72 h after GH treatment. Furthermore, administration of cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both IGF-I and c-myc mRNAs. These results suggest that early induction of c-myc is due to a direct stimulatory effect of GH, and that long-term induction of c-myc was attributable to an indirect effect of GH in which GH-induced secondary proliferative factors may act in an autocrine/paracrine manner. The superinduction of c-myc gene by cycloheximide also indicates that fresh protein synthesis of an intermediate protein was not required for GH-induced c-myc expression. Western ligand blot analysis of IGF-binding proteins revealed that cultured rat articular chondrocytes produced a predominant 41 kDa and a faint 32 kDa form, and that GH significantly stimulated the secretion of the 41 kDa form without affecting expression of the 32 kDa form. Furthermore, a specific IGF-I binding study suggested that the increase in DNA synthesis induced by GH was not associated with changes in affinity or in the number of IGF-I binding sites. These results support the conclusion that the stimulatory effect of GH was mainly mediated by GH-induced IGF-I production in monolayer rat articular chondrocytes. However, it is likely that GH may also have a direct stimulatory effect by inducing c-myc proto-oncogene expression.     

Histomorphometric analysis of bone mass and bone metabolism in growth hormone deficient adult men

Transiliac bone biopsies were obtained from 36 growth hormone (GH) deficient men (mean age ± SD, 28 ± 4 years), of which 13 had an isolated GH deficiency and 23 had partial or complete hypopituitarism. The latter group was adequately substituted for the pituitary hormone deficiencies other than GH. Static histomorphometry was compared with eight controls, and dynamic histomorphometry was compared with six healthy men matched for age. Mean trabecular bone volume was not decreased and bone volume was high (>30%) in ten patients. Osteoid thickness and mineralization lag time were slightly although not significantly higher than in controls. Osteoid surface, mineralizing surface and bone formation rate tended to be lower than in the controls. The eroded surface was significantly higher (p < 0.002) in the GH deficient patients. The results demonstrate that GH deficient patients do not show trabecular osteoporosis. The increased eroded surface together with normal to increased bone volume and bone surface suggests a prolonged reversal phase or a less sufficient coupling phenomenon.     

Growth Hormone Secretion and Bone Mineral Density in Prepubertal Black and White Boys

Racial differences in bone mineral density (BMD) appear to account in part for racial differences in the incidence of osteoporosis and fractures. We previously reported that the greater BMD in adult blacks compared with whites is associated with a higher serum 17 beta-estradiol and greater secretion of growth hormone (GH) in men but not women. To determine whether these racial differences occur in prepubertal boys, we measured spontaneous overnight GH secretion, serum testosterone, 17 beta-estradiol, IGF-I, and IGFBP3, IGF-I/ IGFBP3 ratio, BMD of the total body, forearm, lumbar spine, trochanter, and femoral neck, and lean body mass and body fat in 14 healthy black and 16 white boys ages 6-7 years. Measurements of GH were obtained at 20-minute intervals for 12 hours. Results were analyzed by deconvolution and are expressed as mean +/- SE. Whereas BMD of the hip (0.755 +/- 0.020 vs 0.663 +/- 0.021 g/cm(2), P = 0.0037), trochanter (0.617 +/- 0.014 vs 0.552 +/- 0.018 g/cm(2), P = 0.0102) and femoral neck (0.710+/-0.018 vs 0.6381 +/- 0.021 g/cm(2), P = 0.0157) were significantly greater in black compared with white boys, BMD of the total body (0.768 +/- 0.010 vs 0.741 +/- 0.012 g/cm(2), NS), forearm (0.405 +/- 0.010 vs 0.380 +/- 0.008 g/cm(2), NS), and lumbar spine (0.612 +/- 0.013 vs 0.609 +/- 0.021 g/cm(2), NS) was not different in the two groups. Stepwise regression analysis showed significant correlations between BMD and race at each skeletal site except the lumbar spine and trochanter. Deconvolution analysis revealed no racial difference in any of the GH measurements. Whereas serum testosterone, serum 17 beta-estradiol, and serum IGF-I were not different, serum IGFBP-3 was higher and the molar ratio of serum IGF-l/IGFBP-3 was lower in white than in black males. In summary, prepubertal BMD is higher in black than in white males at the hip, trochanter, and femoral neck, and the racial difference does not result from differences in secretion of GH.     

The relative importance of endocrine versus autocrine/paracrine insulin-like growth factor-I in the regulation of body growth

Body growth is regulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I). The classical somatomedin hypothesis of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have recently abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice displayed a more than 75% reduction in serum IGF-I associated with increased serum levels of GH. In contrast, they demonstrated a normal postnatal growth, indicating that extrahepatic, autocrine/paracrine-acting IGF-I is the main determinant of postnatal growth. Thus, the ”classical” somatomedin hypothesis needs revision. We propose the ”dual somatomedin hypothesis” according to which: (1) autocrine/paracrine IGF-I is the main determinant of postnatal body growth and (2) liver-derived, endocrine-acting, IGF-I exerts negative feedback on GH secretion and possibly also exerts other effects on carbohydrate and lipid metabolism. Received: 5 October 1999 / Revised: 31 December 1999 / Accepted: 8 January 2000     

Growth hormone and insulin-like growth factor-I and mesangial matrix in uremic rats

Combined growth hormone (GH) and insulin-like growth factor-I (IGF-I) therapy has been advocated for clinical use to minimize the diabetogenic effect of GH and enhance their anabolic effects. However, GH has been shown to accelerate the development of glomerular sclerosis in experimental animals and IGF-I mediates the renal effects of GH. The purpose of this study was therefore to examine morphometrically the effects of GH (1 mg intraperitoneally three times a week), IGF-I (50 g/kg body weight subcutaneously twice a day), and combined GH/IGF-I treatments in vivo on mesangial matrix at 3–20 days after 5/6 nephrectomy in 140- to 150-g rats. There were no significant changes in growth and renal function after GH and/or IGF-I treatment. The effects of GH and IGF-I on glomerular size were additive, which were more prominent in juxtamedullary glomeruli. GH induced proportional increases in mesangial area (MA) and glomerular area (GA), whereas IGF-I induced a similar increase in GA without a corresponding change in MA. When compared with GH treatment alone, combined GH/IGF-I treatment resulted in a lesser degree of mesangial expansion despite an enhanced glomerular size. While additional studies are needed to examine the long-term effects of these findings, our results suggest a potentially beneficial effect of combined GH/IGF-I therapy during uremia.     

Investigating the role of the growth hormone–insulin-like growth factor (GH–IGF) axis as a determinant of male bone mineral density (BMD)

IntroductionThe GH–IGF axis has profound effects on bone metabolism and may be important in the etiology of idiopathic osteoporosis. Serum IGF-I is often low in men with osteoporosis, which may be attributable to GH hypo-secretion or hepatic GH insensitivity. We studied the GH–IGF axis in depth to look for evidence to support these hypotheses.Materials and methods28 healthy 60- to 70-year-old men with low, intermediate, or normal BMD were studied. GH secretion was measured by overnight urine collection. GH reserve was assessed by exercise and glucagon stimulation tests. Hepatic IGF-I production was investigated using a GH–IGF-I generation test. Data were analyzed using Pearson’s correlation coefficient, linear regression, and analysis of variance.ResultsSerum IGF-I was reduced in subjects with low BMD (P = 0.009). There was no difference in GH secretion or reserve between the groups. Overall, GH reserve and IGF-I were positively related but this was attenuated in the low BMD group. However, no statistically significant difference in IGF-I generation capacity between BMD groups was found.ConclusionsMen with reduced BMD have low IGF-I but normal GH secretion and reserve. Our data suggested, but could not confirm, hepatic resistance to GH as a mechanism for this association.     

糖尿病患者血清IGF- I JGF-Ⅱ、GH水平与骨质疏松的关系

目的　探讨人类（主要为糖尿病患者）血清胰岛素样生长因子（ＩＧＦ）、生长激素（ＧＨ）与骨质疏松发生发展的关系。方法　通过对不同年龄阶段的 ５１例糖尿病患者与４０ 例对照组的ＢＭＩ、ＩＧＦ、ＧＨ、血糖、ＢＤ、Ｃａ、Ｐ等值的测定，进行对照、比较、研究。结果　糖尿病患者随年龄的增长、血糖的升高、ＢＭＩ的增加、ＧＨ 水平的降低、ＩＧＦ－Ⅰ的分泌水平的减少、骨骼的ＢＤ、Ｃａ、Ｐ等值降低，骨质疏松发生率增加。结论　ＩＧＦ是人类重要而又作用广泛的内分泌因素之一，它不仅具有促细胞分化、增殖活性及胰岛素样作用，与糖尿病关系密切。而且对成骨细胞、破骨细胞即骨质疏松的发生、发展起一定作用。糖尿病病人存在骨代谢障碍即骨质疏松，血中ＩＧＦ、ＧＨ 水平减少的容易导致骨质疏松发生。     

Administration of ghrelin to young uraemic rats increases food intake transiently, stimulates growth hormone secretion and does not improve longitudinal growth.

BACKGROUND: Ghrelin administration stimulates appetite and growth hormone (GH) secretion. Whether these effects are preserved in young individuals with chronic renal failure (CRF) and their potential benefit on growth is questioned. METHODS: Three experiments were performed in subtotally nephrectomized young rats (Nx). (i) Food intake was monitored in CRF rats receiving saline intraperitoneally or a ghrelin dose (30 nmol) shown to increase food intake over 2 and 24 h in rats with normal renal function. (ii) Plasma levels of GH were measured after a dose of intravenous ghrelin (3 nmol) was given to three groups of five rats each: Nx, sham-operated fed ad libitum (SAL) and sham-operated pair-fed with Nx (SPF). (iii) Growth of Nx rats treated with intraperitoneal ghrelin (3 nmol) for 7 days (Nx-Ghr) was compared with that of SAL and Nx groups receiving saline (n=8-10 per group). RESULTS: In CRF rats, the dose of 30 nmol of ghrelin increased food consumption for 2 h (1.3+/-0.2 g vs 0.5+/-0.2 g, P<0.05) but not 24-h food intake (12.5+/-0.6 g vs 12.2+/-0.5 g). Ghrelin (3 nmol) increased plasma levels of GH, which were maximal 10 min after injection, no differences being observed among groups (SAL: 666.2+/-104.6 ng/ml; Nx: 691.6+/-90.7 ng/ml; SPF: 577.8+/-125.4 ng/ml). Return to basal GH levels was delayed in Nx. Ghrelin did not improve body length and weight gains, longitudinal bone growth rate or food intake in the Nx-Ghr group. CONCLUSIONS: In young uraemic rats, ghrelin increases appetite but not 24-h food intake, stimulates GH secretion and does not improve growth.     

Insulin-like growth factor binding proteins as growth inhibitors in children with chronic renal failure

Children with chronic renal failure (CRF) often fail to attain an adult height consistent with their genetic potential. The growth hormone (GH)/insulin-like growth factor (IGF)/growth plate chondrocyte axis has been intensively studied in these children to determine the basis for this growth failure. Evidence suggests that hepatic GH resistance results in deficient expression of IGF-I. However, serum IGF-I levels are usually normal and it is IGF-I action on target tissues which is inhibited, possibly by the presence of excess high-affinity IGF binding proteins (IGFBPs) in CRF serum. In this paper we evaluate the roles of IGFBP-1, -2, and -3 as growth inhibitors in CRF children. The data support a role for each of these IGFBPs as growth inhibitors. Currently, IGFBP-1 meets most criteria expected of a growth inhibitor, but IGFBP-2 and -3 will likely also meet these criteria and may well be important contributors to the growth failure of CRF. Ultimately, many or all of the six IGFBPs may be found to contribute to the excess high-affinity IGF binding sites which are a hallmark of CRF serum and are possible contributors to the growth failure of CRF children.     

Glucocorticoid-induced osteopenia in adolescent heart transplant recipients.

BACKGROUND: Glucocorticoid-induced cushingoid symptoms, including osteopenia and osteoporosis are well-documented in adult heart transplant recipients (HTR). Bone mineral density (BMD) of the axial skeleton is diminished by 10% to 20% within 60 days after transplantation (Tx) and most adult HTR fulfill World Health Organization criteria for osteoporosis (BMD > 2.5 SD below norm). At present, we do not know whether glucocorticoids have similar deleterious effects in adolescent HTR. METHODS: To determine the consequences of glucocorticoid immunosuppression on regional bone mineral density (BMD) and biochemical markers of bone metabolism in adolescent HTR, we studied 19 patients (aged 16 +/- 3) at 19 months (group mean) after Tx. We measured BMD (hydroxyapatite g/cm(2)) of the total body, lumbar spine, and pelvis using dual-energy X-ray absorptiometry (Lunar). Serum levels of bone-specific alkaline phosphatase and pyridinoline cross-links were determined by enzyme immunoassay in serum kits. RESULTS: The BMD of the lumbar spine (-12%), femur neck (-13%), femur trochanter (-12%), and ward's triangle (-16%) were significantly (p < 0.05) lower in adolescent HTR than age- and gender-matched norms. Serum levels of alkaline phosphatase (29 +/- 6 vs 22 +/- 3 U/liter) and pyridinoline cross-links (5.3 +/- 1.1 vs 3.8 +/- 0.7 mmol/liter) were significantly (p < 0.05) elevated in adolescent HTR, compared with age- and gender-matched controls studied in our laboratory. CONCLUSIONS: Our cross-sectional results demonstrate that BMD of the axial skeleton in adolescent HTR is significantly lower (-10% to 20%) than age-matched norms and that serum biochemical markers of bone metabolism are significantly elevated, suggesting accelerated bone turnover.     

生长激素治疗中老年男性骨质疏松的研究进展

骨质疏松是中老年人群中的一种常见病,是中老年人不可避免的一种骨质老化现象。目前全球骨质疏松患者超过1亿人,国内对7省市4.87万人的调查结果显示,60岁以上人群骨质疏松症的患病率为22.6%。骨质疏松可以导致骨折,可明显增加老年人病死率和致残率,调查显示,骨质疏松性骨折后1年内男性死亡率(31﹪)是女性(17﹪)的2倍。有研究表明中老年骨质疏松与生长激素分泌减少有一定关系,小剂量补充治疗后骨骼密度明显增加。本文就生长激素与中老年男性骨质疏松的关系及其补充治疗的可能作用机制作一综述。     

Low Body Size and Elevated Sex-Hormone Binding Globulin Distinguish Men with Idiopathic Vertebral Fracture

Factors predisposing to vertebral fracture in men are less well defined compared with women. Most studies of osteoporosis in men have included patients with low bone mineral density (BMD), with or without vertebral fracture, or have included other fractures. To clarify these associations we investigated sex hormone levels, bone markers, and (indirectly) lean body mass (LBM) in 81 men with idiopathic vertebral fracture. Serum testosterone, estradiol, sex-hormone binding globulin (SHBG), 24-hr urinary creatinine (24-hr UCr), urinary free deoxypyridinoline (UfDPD) and serum type I procollagen carboxy-terminal propeptide, type I procollagen amino-terminal propeptide, type I collagen carboxy-terminal telopeptide, and osteocalcin were measured. SHBG was higher and 24-hr UCr lower in osteoporotic subjects. UfDPD was higher when corrected for 24-hr UCr. Serum bone turnover markers were not significantly increased, nor were serum sex hormones (and free hormone indices) significantly decreased in patients. SHBG levels were inversely related with lumbar spine and femoral neck BMD in both patients and control subjects. Free estradiol index was only correlated with BMD in men with osteoporosis. Body size is lower in men with established osteoporosis. The normal free hormone indices suggest that SHBG does not affect free hormone levels whereas the relationship between SHBG (but not sex hormones) and 24-hr UCr points to a relationship between SHBG and LBM. The association of high levels of SHBG with low levels of LBM may indicate an action via the known inverse relationship of SHBG with IGF-I, though any action through IGF-I probably occurred at an earlier age than that at which the patients presented. Estrogen has no relationship with BMD in normal men but may play a role in men with osteoporosis.     

Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro

Summary In this study we investigated the direct, shortterm effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P<0.001, n=15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P<0.05, n=10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P=0.07, n=9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P=0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.     

Stimulation of growth hormone secretion in children with X-linked hypophosphatemia

X-linked hypophosphatemia is characterized by low serum phosphorus, relative vitamin D deficiency and rickets. Despite adequate metabolic control with oral phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have short stature. Whether growth hormone (GH) deficiency plays a role in short stature in patients with X-linked hypophosphatemia is not known. The purpose of this report was to investigate the response of GH to sequential paired pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH was 3.8±0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225±38 ng/ml and IGF binding protein-3 was 3.0±0.2 mg/l in 16 children studied with X-linked hypophosphatemia. In response tol-dopa and arginine hydrochloride stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I secretory defect.