Biomedical subjects

J Argente

Publications and source records attributed to J Argente.

At least 37 records · Page 2Linked to original sources

PubMed2000

Modifications of growth velocity and the insulin-like growth factor system in children with acute lymphoblastic leukemia: a longitudinal study.

The basis of impaired growth in children with acute lymphoblastic leukemia (ALL) is multifactorial, including the disease itself, infections, undernutrition, and adverse effects of therapy. Because growth is regulated by the GH-insulin-like growth factor (IGF) system, which may be altered in catabolic states, we studied serum IGF-I, free IGF-I, IGF-II, the IGF-binding proteins (IGFBP-1 to -3), and total and free acid-labile subunit (ALS) levels in 26 prepubertal children with ALL at diagnosis (n = 26) and 6 (n = 21), 12 (n = 21), 18 (n = 21), 24 (n = 20), 30 (n = 16), and 36 months (n = 16) after beginning treatment to investigate the effects of disease and therapy on this system and its relationship with growth in these patients. Intensive chemotherapy compromised growth, with a catch-up period beginning when maintenance therapy began and increased growth after stopping therapy. Weight increased 6 months after chemotherapy withdrawal, whereas the body mass index was increased both at 6 months after diagnosis and 6 months after therapy suppression. Serum IGF-I, IGF-II, IGFBP-3, and total and free ALS levels were significantly decreased at diagnosis. Normalization of IGF-II and IGFBP-3 occurred 6 months after diagnosis, and normalization of IGF-I and total and free ALS occurred 1 yr after terminating therapy. IGFBP-1 and IGFBP-2 levels were significantly increased at diagnosis and decreased after stopping therapy. Free IGF-I was elevated throughout the study. IGF and IGFBP-3 levels showed a close relationship to growth velocity at the end of chemotherapy, with this correlation remaining until at least 1 yr after therapy withdrawal. In conclusion, intensive chemotherapy compromises linear growth in prepubertal ALL patients, and this phenomenon is associated with alterations in the IGF system. However, when therapy is reduced or stopped, catch-up growth occurs, but various parameters of the GH-IGF axis remain impaired. This suggests the need for a longer period of follow-up to assess the long-term risks of therapy and disease on this system.

Body Height↗

PubMed2000

Anthropometric parameters and their relationship to serum growth hormone-binding protein and leptin levels in children with acute lymphoblastic leukemia: a prospective study.

OBJECTIVE: The aim of this study was to follow auxological parameters and their relationship to serum growth hormone-binding protein (GHBP) and leptin levels in children with acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: In total, 26 prepubertal children with ALL were studied. We report these data at the time of the clinical diagnosis (n=26) and at 6 (n=21), 12 (n=21), 18 (n=21), 24 (n=20), 30 (n=16) and 36 months (n=16) after beginning treatment. RESULTS: Serum GHBP levels decreased during the first 18 months and returned to normal when therapy was withdrawn. Height SDS increased at 24 months after diagnosis. Weight and the upper arm circumference had increased 6 months after chemotherapy withdrawal, whereas tricipital and subscapular skinfolds had increased both at 6 months after diagnosis and 6 months after therapy had stopped. Therefore, the tendency to become overweight is both an early and a late side-effect of anti-leukemia therapy. A significant positive correlation was found between serum leptin levels and every nutritional anthropometric parameter, with body mass index having the best relationship. However, serum GHBP levels were only correlated with BMI at the end of the study. No correlation was found between leptin and GHBP. CONCLUSIONS: In children with ALL, linear growth is compromised during the acute phase of their illness and therapy; this is probably secondary to a state of partial and transient GH insensitivity. These patients tend to become obese after therapy withdrawal, with leptin being an excellent nutritional marker.

Anthropometry↗

PubMed2000

Effect of neonatal and adult testosterone treatment on the cellular composition of the adult female rat anterior pituitary.

The adult female pituitary has significantly more lactotrophs than that of the male, while the later has a higher percent of somatotrophs. It is clear that GH and prolactin (PRL) gene expression and somatotroph and lactotroph proliferation are modulated by the postpubertal hormone environment; however, the role of the neonatal steroid environment in this process is not known. We have used in situ hybridization to determine the number of GH and PRL mRNA-containing cells, as well as the level of expression of these two hormones, in response to neonatal and adult testosterone treatment. Female rats exposed to testosterone during the neonatal period, adulthood or both periods, as well as normal females and males were used. Exposure to testosterone during the neonatal period significantly increased the percentage of somatotrophs (ANOVA: P<0. 005) and decreased that of lactotrophs in the adult female rat (ANOVA: P<0.001). Adult testosterone treatment had no significant effect on the percentage of somatotrophs. The percentage of lactotrophs was significantly increased by adult testosterone only in those rats also exposed to neonatal testosterone. PRL mRNA concentrations, as reflected by silver grains/cell, were reduced by neonatal testosterone and increased by adult testosterone treatment (ANOVA: P<0.0001). Overall PRL mRNA levels, measured by densitometry, were also reduced by neonatal testosterone exposure, but adult testosterone had no effect (ANOVA: P<0.001). GH mRNA levels per cell, as reflected by silver grains/cell, were increased by adult testosterone, while neonatal testosterone treatment had no effect. Overall GH mRNA levels per unit area, determined by densitometry measurements, were increased by both neonatal and adult testosterone treatment, with the combination of these two treatments resulting in adult females having levels indistinguishable from intact males (ANOVA: P<0.003). These results suggest that, in combination with postpubertal sex steroids, the neonatal gonadal steroid environment plays an important role in determining anterior pituitary hormone synthesis and cellular composition.

Analysis of Variance↗

PubMed2000

[Orofaciodigital syndrome associated with agenesis of the pituitary gland].

UNLABELLED: Oral-facial digital syndrome (OFDS) consists of a group of heterogeneous genetic disorders with different patterns of inheritance. These disorders share facial, oral and digital abnormalities. At least 11 types of this syndrome have been described (I-IX) and the association between OFDS type II and absent pituitary has recently been reported in the case of two brothers. OBJECTIVE: 1. To describe the case of patients with OFDS associated with the absence of the hypophysis and panhypopituitarism. 2. To analyse whether the association between the agenesis of the hypophysis with OFDS represents a new type of this syndrome. PATIENT: An 11-month-old male infant presented with a malformation syndrome with oral (Gothic palate, lobulated tongue with lateral frenulae and hamartomas) facial (a small nose with flattened nasal root and hypoplastic nostrils, small facial skeleton, high forehead, low-implanted ears, stenosis of the choana) and digital malformations (poly- and clinodactyl hands and feet) typical of OFDS. In addition to these findings, at the age of 11 months he had growth retardation (length - 5.9 SD), obesity, mild psychomotor delay, a single upper incisor, micropenis and undescended testes. Endocrinologic studies showed combined GH, TSH, LH and FSH deficiency. Cranial magnetic resonance imaging showed a smooth sella turcica, lacking the pituitary gland, and the absence of the normal sign of neurohypophysis. Replacement therapy with GH and 1-thyroxine was started. SUMMARY: We report a patient with the clinical characteristics of OFDS type II, associated with the absence of hypophysis and panhypopituitarism. CONCLUSION: The infrequent association of agenesis of the pituitary gland and panhypopituitarism with OFDS, and the previous report of two brothers with this syndrome and the same association, suggests that this is a new type of OFDS.

Abnormalities, Multiple↗

PubMed2000

[Lung transplantation and hemophilia. Preoperative considerations].

Lung transplantation is indicated in certain patients with terminal pulmonary disease. We report a case in which a single lung (left) was transplanted to a 16-year-old girl with hemophilia B; she also suffered idiopathic pulmonary fibrosis and had a history of malnutrition, osteoporosis, severe scoliosis, hepatitis C positivity and recurrent bilateral pneumothorax. Treatment with pure factor IX was started the moment the donor lung was available and was continued for 37 days after surgery. Plasma levels of factor IX were kept at 100% during surgery and in the early postoperative period, and over 40% after that time. Correct hemostasis was thus achieved throughout the procedure, with no need for blood products. Patient outcome was satisfactory. The stay in the intensive care recovery ward was 17 days and discharge was 40 days after transplantation. We discuss aspects of hemophilia and lung transplantation, and the influence on malnutrition, chronic steroid treatment and osteoporosis.

Adolescent↗

PubMed1999

Urinary alpha and beta C-telopeptides of collagen I: clinical implications in bone remodeling in patients with anorexia nervosa.

Fragments derived from degradation of type I collagen C-telopeptide (CTX) can be nonisomerized (alpha) or beta-isomerized (beta) depending on the age of bone; i.e., mainly the alpha form is derived from new bone and the beta form from old bone. We have studied 41 female patients with anorexia nervosa (AN), aged 18.5 +/- 2.2 years (range 16-24 years), and with an evolution time between 1.5 and 11 years, and 31 healthy control females (C), with a mean age of 19 +/- 2.3 years (range 16-24 years). The AN patients showed a significant decrease in bone mass, with a mean Z-score of bone mineral density (BMD) of -3.2 +/- 0.8 (range -0.9 to -5.4). The aim of our study was to determine the levels of urinary alpha- and beta-CTX markers of bone resorption, the alpha/beta ratio (alpha/beta), and the level of bone alkaline phosphatase (bAP), a biochemical marker of bone formation, in order to relate them to the degree of osteopenia and the status of bone remodeling. Statistical analysis was by the Mann-Whitney test. The degree of osteopenia correlated with bAP levels (p = 0.0027) but not with the other parameters. Patients with AN were divided into three groups according to their levels of bAP: high (H), normal (N) or low (L). We found that BMD was significantly lower, and alpha- and beta-CTX were significantly higher, in groups H and N than in group L. Bone AP correlated significantly with alpha-CTX (p = 0.0042) and alpha/beta (0.0095) in the controls, but not with beta-CTX, while in AN patients bAP correlated with beta-CTX (p = 0.0000) and with alpha-CTX (p = 0.022) but not with the alpha/beta ratio. The ratio CTX/bAP (resorption/formation) was similar in AN patients and controls. It is concluded that: (1) patients with AN have a high degree of osteopenia which correlated with bAP levels; (2) urinary CTX fragments found in AN patients seem to come mainly from old bone (beta-CTX), while CTX found in healthy adolescent control females come from new bone (alpha-CTX). For this reason, alpha-CTX is more suitable than beta-CTX for measuring bone resorption in controls and beta-CTX is more suitable in patients with AN; (3) the resorption/formation ratio (CTX/bAP) was similar in AN patients and controls. From points (2) and (3) it is possible to suggest that, although bAP reflects bone formation in control females, this marker does not reflect effective bone mineralization in AN patients, a similar feature to that of patients with osteomalacia.

Absorptiometry, Photon↗

PubMed1999

A variation in Bone Alkaline Phosphatase levels that correlates positively with bone loss and normal levels of aminoterminal propeptide of collagen I in girls with anorexia nervosa.

Anorexia nervosa (AN) is a very extended pathology among adolescent girls nowadays. These patients show a high degree of osteopenia; hence, study of their bone remodelling is of great interest. Serum bone alkaline phosphatase (bAP) and aminoterminal propeptide of procollagen I (PINP) provide good sensitivity in the analysis of bone alterations in postmenopausal osteoporosis. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN, and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of the beta-isomer of urinary carboxyterminal propeptide of collagen I (beta-CTX) have also been included. Serum bAP (IRMA) Tandem R-Ostase, Hybritech), PINP (RIA, Orion Diagnostica) and CTX (CrossLaps ELISA, Osteometer) were determined in 41 girls with AN, aged 18.5+/-2.2 years (mean+/-SD) and in 31 healthy control women, aged 19+/-2.3 years. Bone mineral density (BMD) in lumbar spine was measured by DEXA in the AN group. We found that 41 of the 43 patients had BMD z-scores under -2. No significant differences were found in the levels of serum bAP nor in PINP and beta-CTX levels between controls and patients, although values in the AN group were highly variable. All the BMD z-score values were negative, and their absolute value correlates positively with bAP (P = 0.0279) and almost with beta-CTX (P = 0.0921) but not with PINP (P = 0.4627). Bone AP correlates with PINP in control girls (P = 0.017), but not in the AN group (P = 0.3573). Patients with AN were divided into three groups according to their levels of bAP: low (I), normal (II) or high (III). Patients with the highest bAP levels also presented the highest increase in bone resorption, according to their beta-CTX levels, and the highest degree of osteopenia. However, values of PINP were similar in the three groups of patients. The bAP/beta-CTX ratios in subgroups I, II and III of AN patients were 0.035, 0.065 and 0.073, a finding that suggests that bAP is not indicating the real degree of bone mineralization in these patients, because it is a contradiction that the formation/resorption ratio should be higher in the patients who have the highest bone loss. These results could suggest that bone loss in AN is produced by an increase in bone resorption (beta-CTX), without variations in bone matrix formation (PINP); bAP levels are a good marker in the follow-up of osteopenia degree, but not a real indicator of bone mineralization, a similar situation to that of osteomalacia.

Adolescent↗

PubMed1999

Diagnosis of late puberty.

Late puberty is defined as the lack of pubertal development at two standard deviations above the mean age for the general population of the geographical area. In practical terms, this is a chronological age of 14 years for males (testicular volume <4 ml) and 13 years for girls (lack of thelarche). The goal of the assessment is to determine whether the delay or lack of development is due to a lag in normal pubertal maturation or represents an abnormality that must be investigated. Etiologies of pubertal delay and pubertal failure include: a) Constitutional delay of puberty (healthy patients with a clinical history of delayed growth and development; b) Hypogonadotropic states (congenital abnormalities, tumours, endocrinopathies); c) Hypergonadotropic states (chromosomal alterations, syndromes, genetic disorders, radiotherapy/chemotherapy); d) Secondary to chronic illness (organic abnormalities, oncological diseases, malnutrition, eating disorders and endocrinopathies). Diagnostic evaluation must include: a detailed physical examination, including auxological parameters (height and bone maturation), personal and familial antecedents, measurements of general hematological and biochemical parameters, gonadotropins, prolactin, thyroid hormones, sex steroids, growth hormone and growth factors. When necessary, an MRI must be performed. A karyotype is indicated in girls with delayed puberty and short stature and in boys who have small testes and hypergonadotropism.

Adolescent↗

PubMed1998

Bone mineral density in children and adolescents with diabetes mellitus type 1 of recent onset.

There is still controversy over the impact of diabetes control and duration on bone mass and growth parameters in children and adolescents with insulin-dependent diabetes mellitus (IDDM). The aim of this study was to assess bone mineral density (BMD) at axial and appendicular sites, in children with noncomplicated IDDM of recent onset, and its relation to metabolic control and auxological parameters (weight, height, and puberal stage). Fifty-five young Spanish IDDM, otherwise healthy patients (26 males, aged (SD 9.7 +/- 4.3 years) and 29 females, aged (SD 11.2 +/- 3.8 years) were studied. Duration of diabetes was 1-13.8 years. Two hundred eighty-two age-matched, healthy, Spanish children served as controls. HbA1 was assayed by high pressure liquid chromatography (HPLC) and BMD was measured using dual X-ray absorptiometry (DXA) densitometry at the spine and forearm. Results showed a Gaussian BMD distribution of patients according to sex and age, without sexual-stage differences. There was no correlation between BMD and glycated hemoglobin (average life disease or last HbA1 values) or duration of the disease; moreover, no differences in bone mass were found between <3 and >/=3 years of disease duration. Diabetes impact index (mean HbA1 x duration of disease in months) showed no significant influence of diabetes control on BMD. We could not demonstrate any impact of diabetes on BMD and growth parameters in children with IDDM of short duration.

Absorptiometry, Photon↗

PubMed1998

Sexually dimorphic interaction of insulin-like growth factor (IGF)-I and sex steroids in lactotrophs.

Anterior pituitary hormone secretion is sexually dimorphic due partially to gender differences in the postpubertal hormone environment; however, differences in the pituitary's responsiveness to these signals may also play a role. We have used simple and double in situ hybridization to determine whether lactotrophs and somatotrophs from male and female rats respond differently in vitro to growth hormone-releasing hormone (GHRH), somatostatin (SS) or insulin-like growth factor (IGF)-I and whether sex steroids modulate these responses. Cultures were treated with either 17 beta-estradiol (E; 10(-9)M), testosterone (T; 10(-7)M), dihydrotestosterone (DHT; 10(-7) M) or vehicle in combination with either GHRH (10(-7)M), SS (10(-7)M), IGF-I (10(-7)M) or vehicle. Basal mRNA levels of GH, prolactin (PRL) and pituitary transcription factor-1 (Pit-1) did not differ between the sexes. The responses to peptide hormones alone were similar between the sexes, but not in the presence of gonadal steroids. In females, DHT reduced and E increased the stimulatory effect of GHRH and inhibitory effect of SS on GH mRNA levels (two-way ANOVA: P < 0.05), while having no effect in males. An additive effect of E and GHRH on PRL mRNA levels was seen only in males. The E induced rise in PRL mRNA levels was completely inhibited by SS in females, but only partially so in males (two-way ANOVA: P < 0.001). IGF-I inhibited the E induced rise in PRL and lactotroph Pit-1 mRNA levels only in females. These results suggest that sex steroids modulate the pituitary's response to hypothalamic and circulating factors differently in males and females and that this may play a role in generating the sexually dimorphic patterns of pituitary hormone secretion.

Animals↗

PubMed1998

Cellular composition of the adult rat anterior pituitary is influenced by the neonatal sex steroid environment.

Growth hormone (GH) and prolactin (PRL) secretion differ significantly between adult males and females and this is due, at least in part, to the postpubertal hormone environment which affects GH and PRL gene expression, as well as somatotrope and lactotrope proliferation. However, the role of the neonatal steroid environment in this phenomenon is less well understood. We have used in situ hybridization to determine the number of GH and PRL mRNA containing cells, as well as the level of expression of these two hormones and of the pituitary transcription factor 1 (Pit-1). Neonatally castrated male rats that had been exposed to testosterone during the neonatal period, adulthood or during both periods, males castrated as adults, normal adult males and normal proestrous females were used. Orchidectomy of adult rats had no effect on the number of somatotropes or lactotropes, but significantly reduced GH and PRL mRNA levels. Neonatal castration significantly reduced the percentage of somatotropes and increased that of lactotropes in the adult male. In addition, GH and Pit-1 mRNA levels were reduced significantly, but PRL mRNA levels were not modified. Treatment of neonatally castrated males with testosterone during the neonatal period significantly increased the percentage of somatotropes and decreased the percentage of lactotropes compared to vehicle-treated animals. It also increased GH and Pit-1 mRNA levels, but did not affect PRL mRNA levels. Adult testosterone treatment significantly increased the percentage of both somatotropes and lactotropes, as well as GH, PRL and Pit-1 mRNA levels. Treatment of neonatally castrated males with testosterone during both the neonatal and adult periods returned the percentage of somatotropes and lactotropes, as well as GH, PRL and Pit-1 mRNA levels, to that of the intact male. These results suggest that, although the postpubertal steroid environment is important in determining anterior pituitary hormone synthesis and cellular composition, the neonatal steroid environment also plays an important role in this phenomenon.

Animals↗

PubMed1998

[Pseudotumor forms of demyelinating diseases. Report of three cases and review of the literature].

INTRODUCTION AND CLINICAL CASES: We present three patients with unusual clinical findings studied in our hospital, after a period of follow-up of at least two years from the time of diagnosis of their demyelinating condition. We discuss the clinical onset, CT and magnetic resonance findings, neuropathological studies and posterior clinical course. Anatomopathological studies were done in two of the cases, since the diagnoses were not clear and the other paraclinical investigations did not clarify things. DISCUSSION: The presence of large space-occupying lesions or ring-like outlines in myelinating disorders may make it difficult to make a differential diagnosis from other conditions such as neoplasias and abscesses. This may lead to an erroneous initial diagnosis and even to the use of unsuitable, aggressive treatments. CONCLUSIONS: In young patients in whom radiological imaging suggests space-occupying lesions (single or multiple) one should consider the possibility of a primary demyelinating disease of the central nervous system with the appearance of a pseudo-tumour. In certain cases, stereotaxic biopsy should be considered if the diagnosis remains in doubt, rather than begin unsuitable treatment. The fundamental reason for the presentation of our cases is to emphasize that these pseudo-tumoral forms of demyelinating diseases should be considered in diagnosis.

Adolescent↗

PubMed1997

Leptin plasma levels in healthy Spanish children and adolescents, children with obesity, and adolescents with anorexia nervosa and bulimia nervosa.

OBJECTIVES: (1) To investigate normal circulating levels of leptin in children at various stages of pubertal maturation (Tanner stages) according to sex; and (2) to analyze serum leptin levels in pediatric patients with eating disorders (obesity, anorexia nervosa, and bulimia nervosa). STUDY DESIGN: Fasting leptin levels were studied in normal healthy boys and girls throughout development. Obese pediatric subjects and patients with anorexia nervosa were studied at the time of diagnosis and after 6 months and 1 year of treatment for weight reduction or weight recuperation, respectively. Patients with bulimia nervosa were studied at the moment of diagnosis. RESULTS: Leptin levels in both boys and girls vary significantly depending on the maturational stage, being low in both sexes at Tanner stage I and rising significantly by Tanner stage III. In girls, there was a further increase by Tanner stage V and a significant decrease in boys, resulting in a sexual dimorphism in Tanner V subjects. In obese prepubertal patients, leptin levels were significantly elevated at the time of diagnosis and declined significantly with weight loss (ANOVA: p < 0.0001). In anorexia nervosa patients' leptin levels are significantly reduced compared with age- and sex-matched controls (p < 0.0001). These levels remain significantly lower even after recovery of at least 10% of the original body weight and 1 year later. In patients with bulimia leptin levels were reduced at the time of diagnosis but were significantly higher than in patients with anorexia. CONCLUSION: In normal pediatric subjects leptin levels are highly correlated with the body mass index, but this is not the case in eating disorders, where the body mass index is either significantly elevated or reduced. Both age and sex should be taken into consideration when analyzing serum leptin levels.

Adolescent↗

PubMed1997

Immunoblot studies of the acid-labile subunit (ALS) in biological fluids, normal human serum and in children with GH deficiency and GH receptor deficiency before and after long-term therapy with GH or IGF-I respectively.

OBJECTIVE: The aims of this investigation were (a) to study the presence of immunoreactive forms of the acid-labile subunit (ALS) in different human biological fluids, (b) to define the age dependence of serum ALS in normal children and adults and (c) to compare the regulation of ALS by GH or IGF-I in children with GH deficiency (GHD) and GH receptor deficiency (GHRD) before and after 1 year of therapy with GH or IGF-I, respectively. DESIGN AND PATIENTS: Selected human biological fluids from different consenting volunteers and serum from 68 normal children and 5 adults were analysed. Four children diagnosed as GHD and 7 children diagnosed as GHRD were treated with recombinant human (rh) GH at a dosage of 0.05 mg/kg/day s.c. or rhIGF-I at a dosage of 120 micrograms/kg twice daily s.c., respectively, for 12 months. MEASUREMENTS: Immunoreactive forms of ALS were studied by Western immunoblot using a specific rabbit antiserum derived against synthetic human ALS and quantified by laser densitometry analysis. Serum from children with GHD or GHRD were sampled before and at 6 and 12 months of therapy; serum from these patients had been also assayed at baseline for determination of IGF-I and IGF binding protein (IGFBP)-3 by radioimmunoassay and immunoradiometric assay, respectively. RESULTS: An immunoreactive 85 kDa doublet of ALS was detected in serum, plasma, follicular, peritoneal and synovial fluid, but not in urine, seminal plasma, amniotic or extra-embryonic coelomic fluids. Assessment of serum from newborns to adults revealed an age dependence; the ALS doublet was low, but detectable, in newborns, increased during adolescence and remained constant in adulthood. ALS levels were significantly lower in GHD (P = 0.02) and in GHRD children (P = 0.001) than in age-matched controls. Treatment with rhGH in GHD children produced a 2.7-fold increase in serum ALS concentrations at 6 months of therapy (P = 0.01), which was maintained after 1 year of treatment (P = 0.006), leading to normalization of ALS concentrations. In contrast, administration of rhIGF-I to GHRD children failed to increase and normalize serum ALS levels either at 6 or 12 months of therapy. CONCLUSIONS: Immunoreactive forms of acid-labile subunit are present in serum and plasma, as well as in follicular, peritoneal and synovial fluids, suggesting that acid-labile subunit can either cross the capillary barrier or be secreted locally. Acid-labile subunit concentrations are age-dependent with a sharp increase during adolescence, and are reduced in GH deficient and GH receptor deficient children. While treatment with rhGH is able to increase and normalize acid-labile subunit concentrations in GH deficient children, therapy with rhIGF-I fails to increase serum acid-labile subunit levels in GH receptor deficient patients. These data suggest that acid-labile subunit is directly GH-regulated, and that IGF-I cannot increase acid-labile subunit levels, as assessed by Western immunoblot.

Adolescent↗

PubMed1997

Circannual somatostatin gene and somatostatin receptor gene expression in the early post-natal rat pineal gland.

The origin of somatostatin in the pineal gland is controversial as a double origin - neural in pinealopetal nerve fibers and parenchymal corresponding to locally synthesized peptide - is suggested. We have investigated the ontogeny and possible circadian and circannual variations of somatostatin and somatostatin receptor gene expression in the rat pineal gland using RT-PCR. Somatostatin gene expression was observed in the pineal of animals up to 15 days of postnatal life in autumn and winter, but not in prepubertal or adult rats; no transcript was detected during spring and summer at any age and a circadian rhythm was only detected in 15-day-old rats. In situ hybridization confirmed these results. The transcript of the somatostatin receptor gene (SSTR2) was detected at all ages studied with no seasonal variations in its expression, indicating separate regulatory mechanisms. In conclusion, somatostatin and somatostatin receptor mRNAs are expressed in the neonatal rat pineal with circadian and seasonal variations.

Animals↗

PubMed1997

Disturbances in the growth hormone-insulin-like growth factor axis in children and adolescents with different eating disorders.

Numerous endocrine abnormalities of the growth hormone (GH)-insulin-like growth factor axis have been described in patients with both anorexia nervosa and obesity during childhood and adolescence. These alterations include changes in the levels of 24-hour spontaneous GH secretion, high-affinity, low-capacity GH binding protein (GHBP), IGF-I, IGF-II and the IGF binding proteins (IGFBPs). However, the existing information is sometimes confusing and contradictory. Furthermore, little or no data in these pathologies are available concerning IGFBP-2 or free IGF-I. We have analysed the GH-IGF axis in large populations of adolescents with anorexia nervosa and prepubertal children with exogenous obesity. These patients were studied at the time of diagnosis and at two timepoints during nutritional therapy and normal weight recovery. The results of these studies using age- and sex-matched controls are described here.

Adolescent↗

PubMed1997

Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in prepubertal children with exogenous obesity: effect of short- and long-term weight reduction.

We have studied the GH-insulin-like growth factor (IGF) axis in prepubertal children with exogenous obesity at the time of clinical diagnosis and at two time points during weight reduction on a calorie-restricted diet. Spontaneous GH secretion, IGF-I, free IGF-I (fIGF-I), IGF-II, their binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) values at the time of clinical diagnosis (n = 65), after a 25% decrease in the body mass index (BMI) expressed as the SD score (BMI SD score; n = 29), and after a diminution of at least 50% of the initial BMI SD score (n = 9) are reported. GH secretion was significantly reduced at diagnosis, and after a decrease of at least 25% in the initial BMI SD score, it returned to normal in all patients. Total IGF-I levels were not significantly different from those in controls at any point. In contrast, fIGF-1 and IGF-II levels were significantly increased, both at diagnosis and after BMI SD score reduction. Obese patients were hyperinsulinemic at diagnosis and remained so even after a 50% reduction of their BMI SD score. Serum IGFBP-1 and IGFBP-2 levels were significantly decreased at diagnosis and at the two points studied during weight reduction. Serum IGFBP-3 and GHBP levels were increased significantly at diagnosis and returned to normal levels after a reduction in the BMI SD score. A positive correlation between serum GHBP levels and BMI was found in both controls and obese patients. Serum IGFBP-3 levels correlated positively with IGF-I, fIGF-I, and IGF-II in all groups, but these correlations were weaker in the obese patients at diagnosis. IGFBP-2 correlated significantly with IGF-II only in the obese group at diagnosis (r = -0.760; P < 0.0001), but with fIGF-I in all groups. IGFBP-1 was negatively correlated with IGF-I and fIGF-I in all groups. In conclusion, the GH-IGF axis is dramatically altered in patients with exogenous obesity. However, most changes in the peripheral IGF system appear to be independent of the modifications in GH secretion. In addition, in contrast to current thought, not all of the observed abnormalities are reversed with a significant reduction in the BMI SD score.

Body Mass Index↗

PubMed1997

Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation.

We have studied the GH-insulin-like growth factor (IGF) axis in patients with anorexia nervosa at the time of diagnosis and at two points during weight recuperation. We report their spontaneous GH secretion and IGF-I, free IGF-I (fIGF-I), IGF-II, the IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3), and GH-binding protein (GHBP) levels at the time of the clinical diagnosis (n = 50) and after recuperation of between 6-8% (n = 42) and 10% or less of the initial weight (n = 20). Two distinct groups were seen, those who significantly hypersecreted GH and those whose GH secretion was reduced significantly. After recuperation of 10% or more of their initial weight, all patients had a normal GH pattern. Independently of GH secretory dynamics, IGF-1, IGFBP-3, and GHBP serum levels were all significantly decreased at diagnosis, and only GHBP returned to normal after weight recuperation. Serum IGFBP-1 and IGFBP-2 levels were significantly increased at the time of diagnosis and decreased after weight recuperation. The body mass index (BMI) correlated positively with fIGF-I levels and negatively with IGFBP-1 and IGFBP-2 levels, but only after weight recuperation in all cases. Contrary to what is seen in normal individuals, no correlation was found between BMI and serum GHBP levels in anorexia nervosa patients. Serum IGFBP-2 levels had a strong negative correlation with fIGF-I, IGF-II, and the sum of IGF-I and IGF-II, but only at the time of diagnosis. In conclusion, the GH-IGF axis is dramatically altered in patients with anorexia nervosa. Changes in the peripheral IGF system however, appear to be independent of modifications in GH secretion and, in contrast to current thought, not all of the observed abnormalities are rapidly reversed with weight recuperation.

Adolescent↗