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1.
Clin Endocrinol (Oxf) ; 55(6): 789-95, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11895221

ABSTRACT

OBJECTIVE: Intensive studies of oestrogen receptors have suggested extragonadal functions of oestrogen. However, the in vivo extragonadal functions of oestradiol remain unclear because of the lack of an adequate assay system at low concentrations. In this study, we assessed the usefulness of a new ultra-sensitive assay for children. METHODS: Serum oestradiol was measured with an ultrasensitive assay (assayable concentration: 5-1,835 pmol/l: ESTR-US-CT, CIS biointernational, France). Intra- and interassay coefficients of variation at low concentrations (< 36.7 pmol/l) were 8.2 +/- 6.8 (0.1-31.2)% and 8.3 +/- 3.7 (7.5-12.9)%, respectively. SUBJECTS: Sera from 88 healthy children (55 males and 33 females; 1 month to 16 years old) and 31 patients who underwent gonadal suppression therapy were analysed. RESULTS: Age-related changes were observed in both sexes. Serum oestradiol concentrations in childhood decreased slightly compared to those in infancy, then increased at puberty. Most prepubertal children showed oestradiol concentrations lower than 36.7 pmol/l. A study on patients who underwent gonadal suppression therapy revealed oestradiol changes within low concentrations, depending on the stage of the therapy. CONCLUSIONS: The new assay was considered precise enough for the assessment of oestradiol secretion at low concentrations in childhood. Age-related changes in serum oestradiol suggested gonadal activity in the prepubertal period. This assay could be a powerful tool for investigating novel oestradiol functions in vivo.


Subject(s)
Aging/physiology , Estradiol/blood , Adolescent , Analysis of Variance , Child , Child, Preschool , Female , Follicle Stimulating Hormone/blood , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Infant , Longitudinal Studies , Luteinizing Hormone/blood , Male , Puberty/blood , Puberty, Precocious/drug therapy , Radioimmunoassay/methods , Reference Values , Sensitivity and Specificity
2.
Article in English | MEDLINE | ID: mdl-11064284

ABSTRACT

The melanophores in the dermis on scales in the bitterling, Acheilognathus lanceolatus were studies to obtain information about the control mechanism of aggregation and dispersion using intact, membrane-permeabilized and cultured cells. The cultured melanophores showed supersensitivity, namely, they responded to norepinephrine with much higher sensitivity than intact cells. The cultured melanophores failed to respond to high KCl. Melatonin aggregated and adenosine dispersed melanosomes within a cell. Digitonin permeabilized cells showed aggregation with Ca ions and dispersion by cyclic adenosine 3',5'-monophosphate (cAMP) in the presence of ATP. Movement of melanosomes was observed under the high magnification of light microscope and the tracks of each pigment granule were followed. The granules moved fast and linearly during aggregation, whereas they showed to-and-fro movement during dispersion.


Subject(s)
Cell Movement , Fishes , Melanophores/cytology , Melanosomes , Animals , Cell Division , Cell Size , Cells, Cultured , Melanophores/drug effects , Melanosomes/drug effects , Norepinephrine/pharmacology , Potassium Chloride/pharmacology
3.
Horm Res ; 53 Suppl 3: 53-6, 2000.
Article in English | MEDLINE | ID: mdl-10971105

ABSTRACT

Achondroplasia is one of the most common causes of severe rhizomelic dwarfism. We have previously reported the growth-promoting effect of growth hormone (GH) in this disorder. In this expanded clinical study, dose dependency and the long-term effect of GH were also investigated. Prepubertal children with achondroplasia (82 males and 63 females) were randomly divided into 2 groups. Patients were treated with 0.5 IU/kg per week or 1.0 IU/kg per week subcutaneous recombinant human GH. Of 75 patients, the mutational analysis of fibroblast growth factor receptor-3 revealed that G1138A was detected in 70 and G1138C was found in 2. GH increased growth rate and height z score in a dose-dependent manner. GH also increased serum insulin-like growth factor (IGF)-I, IGF-binding protein-3 and osteocalcin. No adverse effects were observed in either group. We conclude that GH therapy is a useful method for improvement of severe growth retardation of achondroplasia.


Subject(s)
Achondroplasia/drug therapy , Growth Hormone/therapeutic use , Protein-Tyrosine Kinases , Achondroplasia/genetics , Achondroplasia/pathology , Body Height/drug effects , Bone Development/drug effects , Cell Differentiation/drug effects , Child , Child, Preschool , DNA/genetics , Female , Humans , Insulin-Like Growth Factor Binding Protein 3/metabolism , Insulin-Like Growth Factor I/metabolism , Male , Mutation/genetics , Mutation/physiology , Receptor, Fibroblast Growth Factor, Type 3 , Receptors, Fibroblast Growth Factor/genetics
4.
Endocr J ; 47(2): 197-201, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10943745

ABSTRACT

We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positive for anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.


Subject(s)
Graves Disease/diagnosis , Immunoglobulins, Thyroid-Stimulating/blood , Antithyroid Agents/therapeutic use , Autoantibodies/blood , Child , Exophthalmos/etiology , Female , Graves Disease/complications , Graves Disease/drug therapy , Humans , Magnetic Resonance Imaging , Propylthiouracil/therapeutic use , Receptors, Thyrotropin/blood , Thyrotropin/blood , Thyrotropin-Releasing Hormone , Thyroxine/blood , Triiodothyronine/blood
5.
Endocrinology ; 141(4): 1317-24, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10746634

ABSTRACT

In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor alpha and beta were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.


Subject(s)
Estrogens/biosynthesis , Genitalia, Female/metabolism , Genitalia, Male/metabolism , Vitamin D/physiology , Animals , Aromatase/genetics , Aromatase/metabolism , Calcium/pharmacology , Estradiol/blood , Estradiol/pharmacology , Female , Follicle Stimulating Hormone/blood , Gene Expression , Genitalia, Male/abnormalities , Genitalia, Male/pathology , Luteinizing Hormone/blood , Male , Mice , Mice, Knockout/genetics , Receptors, Calcitriol/genetics
6.
Bone ; 26(3): 281-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10710002

ABSTRACT

Microgravity induces significant and progressive bone loss in both humans and animals. This is the consequence of disturbed bone remodeling. We performed a bed rest experiment to simulate microgravity and tried to clarify bone metabolism by measuring biochemical markers of bone turnover. Six healthy volunteers participated in 120 days of bed rest. The parameters of calcium homeostasis, calcitropic hormones, and biochemical markers of bone turnover were examined. After ambulatory control evaluation, all subjects underwent 120 days of bed rest. Metabolic evaluation was performed in a baseline period, and on days 7, 16, 50, 72, 92, and 108 during bed rest, and on days 10 and 25 during a recovery period. Bed rest induced an increase in urinary calcium (Ca) excretion and serum Ca and bone resorption markers. Urine pyridinoline, deoxypyridinoline, and type I collagen cross-linked N-telopeptide increased more rapidly than urinary Ca excretion and serum Ca. Tartrate-resistant acid phosphatase (TRAP) increased even in the recovery period. Carboxy-terminal propeptide of type I collagen, a bone formation marker, significantly decreased on days 50, 92, and 108 of bed rest. These changes of biochemical markers of bone metabolism, except for TRAP, rapidly returned toward control levels in the recovery period. Immunoreactive parathyroid hormone showed a modest decrease during bed rest and a significant increase in the recovery period. Insulin-like growth factor I (IGF-I) and its binding protein, insulin-like growth factor binding protein-3, increased during bed rest, indicating the possibility of resistance to IGF-I in bones under reduced mechanical stress and strain. Bone loss from unloading results from the combination of acceleration of bone resorption and subsequent retardation of bone formation.


Subject(s)
Biomarkers , Bone Remodeling , Hypokinesia/metabolism , Adult , Bone Resorption , Calcium/blood , Calcium/urine , Humans , Hypokinesia/physiopathology , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/metabolism , Male , Parathyroid Hormone/blood
7.
Horm Res ; 51 Suppl 3: 113-5, 1999.
Article in English | MEDLINE | ID: mdl-10592454

ABSTRACT

Human growth hormone (hGH) is an essential therapeutic drug for the treatment of GH deficiency. The development of recombinant GH using a pen injection system has enabled easy and safe treatment of GH-deficient patients; however, the process of dissolving hGH in the powder form is complicated and dangerous. In this study, we investigated the usefulness of a newly developed liquid form of hGH (Norditropin((R)) SimpleXx(TM)) in the treatment of 51 patients with GH deficiency. Fifteen previously untreated patients with GH deficiency were treated with liquid hGH (group A), and 36 patients who had previously used hGH in the powder form were changed to the liquid form (group B). Both groups were treated with liquid hGH 0.5 IU/kg per week for 6 months. The growth rate of patients in group A increased from 4.0 +/- 2.4 cm/year to 9.2 +/- 2.9 cm/year. The patients in group B continued to grow at the same rate as before using the liquid hGH therapy. Questionnaires to the patients in group B demonstrated that 85% preferred the convenience of using the new liquid form of hGH. Our results indicate that liquid hGH has similar efficacy to that of powder hGH, but its improved convenience may have a beneficial effect on patient compliance.


Subject(s)
Human Growth Hormone/administration & dosage , Human Growth Hormone/deficiency , Body Height , Child , Child, Preschool , Female , Growth , Human Growth Hormone/therapeutic use , Humans , Injections/instrumentation , Male , Pain , Patient Compliance , Solutions , Surveys and Questionnaires
9.
Acta Paediatr Suppl ; 88(428): 118-20, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10102070

ABSTRACT

Achondroplasia is a common skeletal dysplasia with severe growth retardation. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR3) were identified in patients with achondroplasia. In the present study, 70 of 75 Japanese patients with achondroplasia were found to have a G1138A mutation in FGFR3, and two patients had a G1138C mutation. Growth hormone therapy was given to 145 patients with achondroplasia. Significant dose-dependent effects on skeletal growth were obtained, with no long-term adverse effects.


Subject(s)
Achondroplasia/drug therapy , Achondroplasia/genetics , Body Height/drug effects , Human Growth Hormone/administration & dosage , Receptors, Fibroblast Growth Factor/genetics , Achondroplasia/complications , Child , Child, Preschool , Female , Follow-Up Studies , Growth Disorders/drug therapy , Growth Disorders/etiology , Humans , Male , Molecular Biology , Mutation , Treatment Outcome
10.
Bone ; 22(5 Suppl): 145S-147S, 1998 May.
Article in English | MEDLINE | ID: mdl-9600772

ABSTRACT

Bone loss during space flight may be induced by decreased activity of bone formation. To explore a new method for the bone loss in microgravity, the effects of insulin-like growth factor I (IGF-I), a potent stimulator for osteoblast activities, were studied in in vitro and in vivo system. The complex of IGF-I and its specific binding protein, IGFBP-3, may stimulate the osteoblastic activities via prolonged serum half life and increased cellular association of IGF-I. In an ovariectomy combined with neurectomy model, this complex stimulated bone turnover. IGF-I/IGFBP-3 may be a candidate for the treatment of bone loss induced by the microgravity.


Subject(s)
Bone Density , Bone Development/physiology , Insulin-Like Growth Factor Binding Protein 3/physiology , Insulin-Like Growth Factor I/physiology , Space Flight , Animals , Bone Development/drug effects , Cell Division , Cells, Cultured , Drug Combinations , Humans , Insulin-Like Growth Factor Binding Protein 3/pharmacology , Insulin-Like Growth Factor I/pharmacology , Osteoblasts/drug effects , Recombinant Proteins , Weightlessness
11.
Acta Paediatr Jpn ; 39(4): 521-7, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9316304

ABSTRACT

Osteogenesis imperfecta (OI) is an inheritable disorder characterized by bone fragility with various symptoms of connective tissue disorders. OI is commonly classified by Sillence's classification into four types according to the clinical features. The cardinal symptom is pathologic fracture, which is often recognized before birth, is frequent during infancy and childhood, then decreases at puberty. Bone mineral density is markedly decreased in OI, especially of the lumbar spine. Bone deformities are frequently observed in the long bones of the extremities, and spinal deformities and compression fractures are also common. Growth retardation is extremely severe, especially in type III. Calcitonin has been the most common therapy for OI. Recently, bisphosphonates have been found to be potent drugs that increase bone mass in OI patients. To prevent further fracture or bone deformity, appropriate orthopedic managements, including intramedullary rodding, are critically important. Growth hormone is effective in stimulating bone growth during childhood. The pathogenesis of OI is quantitative or qualitative abnormalities of type I collagen. The clinical features of each type usually correspond to the type of mutation. Several possibilities for gene therapy have been proposed.


Subject(s)
Osteogenesis Imperfecta , Adolescent , Bone Density , Child , Child, Preschool , Collagen/genetics , Collagen/metabolism , Diagnosis, Differential , Humans , Infant , Infant, Newborn , Male , Orthopedic Fixation Devices , Osteogenesis Imperfecta/diagnosis , Osteogenesis Imperfecta/genetics , Osteogenesis Imperfecta/pathology , Osteogenesis Imperfecta/therapy
12.
J Clin Endocrinol Metab ; 82(7): 2056-61, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9215272

ABSTRACT

Serum bone alkaline phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immunoradiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal children (207 males and 156 females, age 0-18 yr) and in 20 GH-deficient children (age 5-13 yr) who showed significant bone growth during GH therapy. We found the following results. 1) There were no significant circadian variations in serum B-ALP levels (coefficients of variation: 2.10-9.66%). 2) In normal children, serum B-ALP levels were high in infants and gradually declined and increased again during puberty. During the pubertal period, the highest serum B-ALP values were observed at midpuberty (stage 3 of breast and pubic hair development and 4-12 mL of testicular volume). 3) Serum B-ALP levels were significantly correlated with levels of the carboxy-terminal propeptide of type 1 procollagen (r = 0.447, P < 0.0001) and osteocalcin (r = 0.433, P < 0.0001). 4) After beginning GH therapy, serum B-ALP levels increased significantly; a 26% increase in serum B-ALP level was observed after 3 months of GH therapy. 5) The ratio between serum B-ALP level after 3 months of GH therapy and before GH therapy was positively correlated with the GH-induced improvement in the height SD score (height SD score after 1 yr of GH therapy minus that before GH therapy) and improvement in the height velocity SD score (height velocity SD score during GH therapy minus before GH therapy) (r = 0.531, P < 0.05 and r = 0.608, P < 0.01, respectively). 6) The increment of SD score in serum B-ALP level after 1 yr of GH treatment was also significantly correlated with that for bone mineral density after 1 yr of GH therapy (r = 0.663, P < 0.005). These results show that B-ALP levels are a useful marker for bone formation because B-ALP levels increased when the growth rate accelerated. Serum B-ALP is a potential predictor of the effectiveness of GH therapy, because the serum level after 3 months of GH therapy reflects the outcome of 1 yr of GH therapy.


Subject(s)
Alkaline Phosphatase/blood , Bone and Bones/enzymology , Growth Hormone/deficiency , Isoenzymes/blood , Osteogenesis/physiology , Adolescent , Age Factors , Animals , Biomarkers/analysis , Body Height , Child , Child, Preschool , Circadian Rhythm , Female , Growth Hormone/therapeutic use , Humans , Infant , Infant, Newborn , Male , Osteocalcin/blood , Osteogenesis/drug effects , Peptide Fragments/blood , Procollagen/blood , Sex Factors
14.
J Bone Miner Res ; 10(11): 1698-704, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8592946

ABSTRACT

The hypophosphatemic mouse, the murine homologue of X-linked hypophosphatemia, is characterized by renal defects in phosphate reabsorption and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) production and by an osteoblast dysfunction. In view of the potential importance of insulin-like growth factors (IGFs) in the regulation of these processes and the role of IGF-binding proteins (IGFBPs) as modulators of IGF action, we asked whether Hyp mice have alterations in IGFs or IGFBPs. Using specific radioimmunoassays and Western ligand blot analysis, we evaluated serum levels of IGFs (IGF-1 and IGF-II) and IGFBPs, respectively, in normal and Hyp mice. We also examined the effect of dietary phosphatase on these parameters. Serum levels of IGF-1 and IGF-II in Hyp mice were not significantly different from those in normal mice, but IGFBP-3 levels were significantly lower (70% of normal, p < 0.05) in the mutant strain. The other IGFBP species appear unchanged. Phosphate supplementation normalized serum phosphate levels in Hyp mice and elicited a significant decrease in serum IGF-I levels (23%, p < 0.05) and a further deduction in IGFBP-3 (22%, p < 0.02). Phosphate deprivation induced hypophosphatemia IGF-II. The present results indicate that the low serum IGFBP-3 activity in Hyp mice is not related to hypophosphatemia per se. Based on the documented effects of parathyroid hormone (PTH) on IGF-I and IGFBP-3, we propose that the secondary hyperparathyroidism displayed by Hyp mice and its exacerbation by phosphate supplementation may contribute to low IGFBP-3 levels in control Hyp mice and to the decreases in serum IGF-I and IGFBP-3 in phosphate-supplemented Hyp mice.


Subject(s)
Hypophosphatemia, Familial/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor I/metabolism , Analysis of Variance , Animals , Blotting, Western , Diet , Hypophosphatemia, Familial/physiopathology , Male , Mice , Mice, Inbred C57BL , Phosphates/administration & dosage , Phosphates/metabolism , Radioimmunoassay
16.
J Pediatr ; 123(2): 264-8, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8345424

ABSTRACT

A male infant with malignant osteopetrosis was treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. Therapy with 1 alpha-hydroxyvitamin D3 increased the serum calcium level despite the markedly elevated serum level of 1 alpha, 25-dihydroxyvitamin D before treatment. Recombinant human interferon gamma increased neither the bone mineral nor matrix turnover, and was not tolerated because of bone marrow suppression.


Subject(s)
Hydroxycholecalciferols/therapeutic use , Interferon-gamma/therapeutic use , Osteopetrosis/therapy , Dose-Response Relationship, Drug , Drug Therapy, Combination , Humans , Hydroxycholecalciferols/pharmacology , Infant , Interferon-gamma/pharmacology , Male , Osteopetrosis/diagnosis , Osteopetrosis/metabolism , Recombinant Proteins
17.
J Pediatr Endocrinol ; 6(1): 45-52, 1993.
Article in English | MEDLINE | ID: mdl-8374688

ABSTRACT

Achondroplasia is one of the most commonly known types of skeletal dysplasia in the adult leading to short stature. Before beginning growth hormone (GH) treatment of short stature in patients with achondroplasia, we evaluated their growth pattern and their hypothalamic-pituitary function, including GH secretion. We studied 22 patients with achondroplasia (7 males and 15 females: age range, 3 to 12 years). The z-score of their height at admission was -5.4 +/- 1.2 (mean +/- SD), and that of their annual height gain before admission was -3.1 +/- 1.3 (mean +/- SD). GH response to provocative tests was normal in all patients except five: four showed subnormal (< 10 ng/ml) response to L-Dopa stimuli, and one patient showed subnormal (< 20 ng/ml) response to GRF stimuli. The mean GH concentration during sleep was found to be low (< 5 ng/ml) in three patients. These three patients were suspected to have latent GH deficiency, as they also showed a markedly low IGF-1 level and marked delay of bone age. LH, FSH, TSH, and cortisol response to provocative tests were normal in all the patients. We treated this group of patients with recombinant human GH (1 IU/kg/week). In 18 patients who were treated with GH for more than 6 months, height velocity during GH therapy was significantly increased compared to that before GH therapy (4.1 +/- 0.8 cm/year vs 7.2 +/- 1.4 cm/year). We conclude that parameters reflecting hypothalamic-pituitary function, particularly GH secretion, should be examined in achondroplasia patients, and that GH treatment may be beneficial in the treatment of short stature in achondroplasia.


Subject(s)
Achondroplasia/drug therapy , Growth Hormone/therapeutic use , Achondroplasia/blood , Achondroplasia/physiopathology , Body Height/physiology , Child , Child, Preschool , Female , Follicle Stimulating Hormone/blood , Growth Hormone/administration & dosage , Growth Hormone/blood , Humans , Hydrocortisone/blood , Hypothalamus/physiology , Injections, Subcutaneous , Insulin-Like Growth Factor I/analysis , Luteinizing Hormone/blood , Male , Pituitary Gland/physiology , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Thyrotropin/blood
18.
Acta Paediatr ; 81(11): 907-11, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1361379

ABSTRACT

Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) concentrations were determined in 36 insulin-dependent diabetic children aged 4-18 years with a duration of diabetes ranging from 1 month to 14 years. Abnormal urinary GP-DAP concentrations were found in 19 of the 36 patients. Twelve of 27 patients without microalbuminuria also had increased urinary concentrations of GP-DAP. There was a significant correlation between urinary GP-DAP and plasma fructosamine (r = 0.52, p < 0.001). Our data suggest that urinary GP-DAP may be used as a marker for diabetic nephropathy. However, there is also a possibility that increased urinary GP-DAP concentrations are functionally related to poor metabolic control. Longitudinal studies are needed to establish the clinical usefulness of urinary GP-DAP.


Subject(s)
Diabetes Mellitus, Type 1/urine , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/urine , Adolescent , Age Factors , Albuminuria/epidemiology , Albuminuria/etiology , Albuminuria/urine , Biomarkers/urine , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/urine , Dipeptidyl Peptidase 4 , Evaluation Studies as Topic , Fructosamine , Hexosamines/blood , Hospitals, University , Humans , Japan/epidemiology , Prevalence , Regression Analysis
19.
J Clin Endocrinol Metab ; 75(4): 1104-9, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1400878

ABSTRACT

To establish a sensitive marker for bone formation we have developed a sandwich enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide. Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr, and in 23 GH-deficient children treated with GH. The serum levels of the propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE) micrograms/L in boys and 1.53 +/- 0.23 micrograms/L in girls. The peak value occurred at the age of 13 yr in boys (2.91 +/- 0.42 micrograms/L) and 11 yr in girls (2.34 +/- 0.34 micrograms/L). The serum intact OC levels in prepubescent boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 micrograms/L, respectively, and these levels increased to 41.0 +/- 3.7 micrograms/L in boys aged 13 yr and to 27.0 +/- 2.5 micrograms/L in girls aged 11 yr. In the GH-deficient patients, a 2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC levels after 1 month of GH therapy correlated with the growth response after 12 months of GH therapy (r = 0.660 and P < 0.01, for propeptide; r = 0.537 and P < 0.01 for intact OC). These results show that since both propeptide and intact OC in serum were increased when the growth rate was elevated, these peptides are sensitive markers of bone formation. Serum levels of these peptides, particularly propeptide, after 1 month of GH therapy might be a helpful predictor of the growth response to long term GH therapy.


Subject(s)
Bone Development/physiology , Calcium-Binding Proteins/blood , Growth Disorders/blood , Growth Hormone/deficiency , Growth Hormone/therapeutic use , Osteocalcin/blood , Protein Precursors , Adolescent , Adult , Biomarkers/blood , Bone Development/drug effects , Child , Child, Preschool , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Female , Growth Disorders/drug therapy , Growth Disorders/physiopathology , Humans , Male , Regression Analysis
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