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Biomedical subjects

J Argente

Publications and source records attributed to J Argente.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1996

Sex steroid effects on the development and functioning of the growth hormone axis.

1. The secretory pattern of growth hormone (GH) is sexually dimorphic in the adult rat. However, this difference between the sexes does not become apparent until after the onset of puberty, suggesting that pubertal sex steroids play an important role in the manifestation of this phenomenon. 2. We have addressed the question as to whether there exists a sexual dimorphism in the hypothalamic neuropeptides that regulate GH release from the anterior pituitary, i.e., somatostatin (SS) and growth hormone-releasing hormone (GHRH). In addition, we have investigated whether the developmental changes in the GH secretory pattern are correlated with changes in these neuropeptides. The effect of testosterone treatment on SS and GHRH neurons during both the neonatal period and adulthood have also been studied. 3. We have found that the synthetic capacity, as reflected in relative messenger RNA (mRNA) levels, of both SS and GHRH neurons changes throughout development in both male and female rats. These mRNA levels are sexually dimorphic at certain times during maturation and can be modulated by changes in testosterone levels, suggesting that sex steroid modulation of these two neuropeptide systems could at least partially account for the sexual dimorphism seen in the adult GH secretory pattern. 4. The neonatal steroid environment has also been suggested to be involved in the generation of the final adult GH secretory pattern, although the mechanisms underlying this effect are even less well understood. In support of the hypothesis that the neonatal steroid environment plays an important role in organizing the GH axis, we have found that the number of GHRH neurons in the adult brain, as well as their sensitivity to adult steroids, is modulated by neonatal testosterone treatment. The number of SS neurons in the periventricular and paraventricular nuclei were not modulated by neonatal steroids; however, the synthetic capacity of these neurons does appear to be influenced by the neonatal steroid environment. 5. These studies suggest that both the neonatal and adult sex steroid environments influence the adult GH secretory pattern by modulating GHRH and SS neurons.

Animals↗
PubMed1996

Ontogeny of pituitary transcription factor-1 (Pit-1), growth hormone (GH) and prolactin (PRL) mRNA levels in male and female rats and the differential expression of Pit-1 in lactotrophs and somatotrophs.

Pituitary transcription factor-1 (Pit-1 or GHF-1), a transcription factor specific to the anterior pituitary, is involved in the expression and regulation of the growth hormone (GH) and prolactin (PRL) genes. Post-pubertally, the expression of both GH and PRL becomes sexually dimorphic with males having higher GH levels and females higher PRL levels; however, little is known about the postnatal regulation of their common transcription factor. Furthermore, whether the Pit-1 gene is differentially expressed in somatotrophs and lactotrophs remains to be elucidated. In this study, we used in situ hybridization histochemistry to examine Pit-1, GH and PRL mRNA levels in the anterior pituitaries of male and female rats throughout development (0, 5, 10, 20, 30, 40 and 60 days of age) to determine when GH and PRL production becomes sexually dimorphic and if this is accompanied by a dimorphism in Pit-1 gene expression. In addition, the level of Pit-1 mRNA was determined separately in both GH mRNA and PRL mRNA containing cells during the various developmental stages. We found that in both males and females the mRNA levels of Pit-1, GH and PRL remain relatively unchanged until around the time of pubertal onset (30-40 days) when there is a significant increase in all three mRNA species, which is followed by a decrease to adult levels. Also around the time of puberty, both GH and PRL mRNA levels become sexually dimorphic, with males having higher levels of GH mRNA and females higher PRL mRNA levels. In contrast, at no time during development were overall Pit-1 mRNA levels found to differ between the sexes. However, when Pit-1 mRNA content was measured separately in specific cell types, significant differences between the sexes became evident. Throughout development Pit-1 mRNA levels are higher in lactotrophs of females than in those of males, whereas in somatotrophs males have higher Pit-1 mRNA levels than females. Furthermore, within a sex there is differential expression of Pit-1 in the two cell types with females having significantly higher levels of Pit-1 in lactotrophs than in somatotrophs and males having higher levels in somatotrophs than in lactotrophs. These data support the hypothesis that a sexual dimorphism exists in the expression and pituitary specific transcription factor Pit-1; however, this dimorphism is not manifest as a difference in overall mRNA levels, but in the differential expression of this gene in lactotrophs and somatotrophs.

Aging↗
PubMed1996

In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment.

Pituitary transcription factor-1 (Pit-1 or GHF-1) is a transcription factor specific to the anterior pituitary and is involved in the expression and regulation of the growth hormone (GH), prolactin (PRL) and thyroid-stimulating hormone (TSH) beta-subunit genes. The expression of these three genes can be modulated by changes in the hormone environment and it is thought that some of these effects are mediated through Pit-1, but little is known about the physiological regulation of this transcription factor. Therefore, we first asked whether Pit-1 gene expression is modified as a result of changes in the in vivo gonadal steroid environment and if this could be correlated with changes in GH and/or PRL mRNA levels. Secondly, we sought to determine if sex steroids affect the mRNA levels of these three peptides by acting at the level of the pituitary and whether these effects are androgen or estrogen mediated. Finally, how sex steroids modulate the response of these three genes to the hypothalamic neuropeptides growth hormone-releasing hormone (GHRH) and somatostatin (SS) was analyzed. To this end, we compared Pit-1, GH and PRL mRNA levels in the anterior pituitary of intact, castrated, and castrated testosterone-replaced adult male rats. In addition, primary cultures of adult male pituitaries were used to study the direct effects of both androgens and estrogens on Pit-1, GH, and PRL mRNA levels. In situ hybridization histochemistry was used to compare relative levels of Pit-1, GH and PRL mRNA. Densitometric analysis of the in vivo studies showed that castration resulted in a 57, 40 and 55% decline in Pit-1, GH and PRL mRNA signal levels, respectively. Furthermore, replacement with testosterone (T) at the time of castration completely prevented the decline in all three mRNA species (ANOVA: Pit-1 mRNA, p < 0.0001; GH mRNA, p < 0.0001; PRL mRNA, p < 0.0001). In vivo, both T (10(-7) M) and estradiol (10(-9) M) were capable of stimulating Pit-1 mRNA and PRL mRNA levels, while dihydrotestosterone (DHT; 10(-7) M) had no effect. There was no effect of any of these steroid treatments on GH mRNA levels in vitro. Addition of GHRH to the cultures increased GH mRNA levels, as well as those of Pit-1 and PRL, and SS had the opposite effect on GH mRNA levels. Whereas the GH response to GHRH was not significantly modified by exposure to sex steroids, the effect of SS was. The presence of sex steroids was capable of modifying the Pit-1 and PRL responses to both GHRH and SS. These results clearly indicate that changes in circulating levels of sex steroids modulate the expression of Pit-1 in the anterior pituitary and that these changes can be correlated with commensurate modifications in GH and PRL mRNA levels. Furthermore, the effect on both Pit-1 and PRL mRNA levels occurs, at least in part, at the level of the anterior pituitary and is an estrogen-receptor-mediated event. In contrast, the effects of gonadal steroids on GH mRNA levels are less direct and are most likely mediated at the level of the hypothalamus, as well as through modulation of the response of the somatotroph to hypothalamic factors. We conclude that the transcription factor Pit-1 is actively regulated physiologically and may be involved in mediating some of the effects of sex steroids and hypothalamic factors on the synthesis of certain anterior pituitary hormones.

Animals↗
PubMed1996

The growth hormone axis: control and effects.

Many important advances in our understanding of the growth hormone (GH) axis have occurred during the last decade. A number of neurotransmitters and neuropeptides are implicated in the control of growth hormone-releasing hormone (GHRH) and somatostatin release; however, the role of many of these, such as serotonin, gamma-aminobutyric acid and dopamine, is still a matter of discussion. As a newly isolated hypothalamic peptide with a possible role in the control of GH secretion, pituitary adenylate cyclase activating peptide has received considerable attention. Synthetic hexapeptides that stimulate GH release (GH-releasing peptides 1, 2 and 6) have been identified. Pituitary-specific transcription factors involved in the expression of the GH gene have been identified, the GHRH receptor gene has been cloned, as well as a number of somatostatin receptor genes, and advances in our understanding of the insulin-like growth factor-binding proteins, and growth hormone-binding proteins have been made.

Animals↗
PubMed1996

The role of glia in the neuroendocrine hypothalamus: possible implications in hormone secretion.

Recent evidence indicates that glia may play a significant role in the link between the endocrine and nervous systems. Gonadal steroids modulate astroglia morphology, differentiation and gene expression in different brain areas. Hormonal effects on glia may have important consequences for neuronal development, metabolism and activity, for the formation and plasticity of synaptic connections, and for the modulation of hypothalamic hormone release. Perinatal and adult testosterone levels modulate the expression of the specific astroglia cytoskeletal marker glial fibrillary acidic protein in the arcuate nucleus of the rat hypothalamus. These changes parallel hormonal effects on the expression of growth hormone-releasing hormone (GHRH) and the number of GHRH neurones in the arcuate nucleus. The effects of testosterone and its metabolite oestradiol on hypothalamic neurones may be dependent on the release by hypothalamic astroglia of insulin-like growth factor I, a molecule involved in the control of growth hormone secretion.

Adult↗
PubMed1996

Insulin-like growth factor I, insulin-like growth factor binding proteins, and growth hormone binding protein in Spanish premature and full-term newborns.

The normal values of insulin-like growth factor I (IGF-I), IGF-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), and the high-affinity growth hormone binding protein (GHBP) are not well established in large series of healthy fullterm newborns. We report the normative data for IGF-I, IGFBP-I, IGFBP-3, and GHBP in 271 normal Spanish full-term newborns, born between 37 and 42 weeks of gestation, and compare these results with the same parameters studied in 39 premature infants. Furthermore, we report the relationship between results found in the normal full-term newborns and those of 252 healthy prepubertal (Tanner stage I) Spanish children. Serum GHBP, IGF-I, and IGFBP-3 levels are very low in the premature infant and show a significant increase in full-term newborns, and continue to decline during childhood (p < 0.001; analysis of variance). A positive correlation between GHBP, IGF-I, and IGFBP-3 versus gestational age was observed. In contrast, we found a negative correlation between IGFBP-I and gestational age. There is a direct relationship between the ponderal index and IGF-I and IGFBP-3. When the group of premature newborns was divided into infants born before or after 32 weeks of gestation, we found higher levels of IGF-I and IGFBP-3 (p < 0.01 and p < 0.05, respectively, by Student's test) in the group with the higher gestational age; however, the IGFBP-I level was lower in this group (p < 0.001 by Student's t test), with no differences seen in serum GHBP concentrations. The presence of IGFBPs in the premature infant suggests that they are important modulators of IGF-I action during fetal growth and development.

Carrier Proteins↗
PubMed1996

Growth hormone-releasing peptides: clinical and basic aspects.

Growth hormone (GH)-releasing peptides (GHRPs), a family of synthetic oligopeptides which stimulate GH release, were identified more than a decade ago. The effects of these peptides on GH release have been described in vivo and in vitro, in both animals and humans, using various doses and administration routes. It is generally accepted that GHRPs stimulate the release of GH by acting at the level of the pituitary through a receptor different to that for the endogenous GH-releasing hormone (GHRH). In addition, it has been reported that there are specific binding sites for these peptides in the hypothalamus and that systemic administration of GHRPs increases the expression of the immediate early gene c-fos in a subpopulation of hypothalamic neurons. However, the identity of these hypothalamic neurons and the mechanism of action of GHRPs at both the hypothalamic and pituitary levels remain unknown. One interesting aspect of GHRPs is that they are orally active and this phenomenon has been demonstrated in both animals and humans. Furthermore, these drugs stimulate GH secretion in humans dose-dependently with the magnitude and duration of this response being comparable to that seen with an intravenous peptide bolus. We have studied the oral activity of GHRP-2 on GH release in normal children. In addition, we have analyzed the response to GHRP-2 of obese adolescents, as well as the effects of an intravenous bolus of GHRH alone and GHRH plus GHRP-2. Orally administered GHRP-2 stimulates GH secretion in normal children and, although it seems that this drug is more potent in girls, there were no statistical differences between the groups. Characteristically, GH levels started to increase by 15 min, peaked at 60 min and returned to basal concentrations by 180 min. The effect of GHRP-2 was synergistic with GHRH 1-29 NH2. In addition, obese subjects appeared to have a greater response to this peptide than did normal controls. To study the effects of GHRPs on hypothalamic GHRH and somatostatin neurons, female dwarf rats (dw/dw) were treated continuously with GHRP-6 (1 mg/kg per 24 h) for 14 days. In situ hybridization for GHRH and SS was performed. We found that GHRP-6 stimulated GHRH mRNA levels in the posterior arcuate nucleus (ARC), with no significant effect in the anterior ARC or ventromedial hypothalamic neurons. SS mRNA levels in the posterior periventricular nucleus (PeN) were decreased after GHRP-6 treatment, while no effect was seen in the anterior PeN, ARC, or lateral paraventricular nucleus. These results suggest that GHRP-6 treatment modulates hypothalamic neurons controlling GH secretion; however, whether this effect is direct or mediated through another factor remains to be elucidated.

Animals↗
PubMed1996

Interaction of the signalling pathways of insulin-like growth factor-I and sex steroids in the neuroendocrine hypothalamus.

Among the numerous endocrine signals that affect the central nervous system, sex steroids play an important role. It has been recently postulated that part of the effects of these hormones on the brain may be mediated by trophic factors, such as insulin-like growth factor I (IGF-I). Both estradiol and IGF-I increase the survival and differentiation of developing fetal rat hypothalamic neurons in culture. The effect of estradiol is blocked by the pure estrogen receptor antagonist ICI 182,780, by an antisense oligonucleotide to the estrogen receptor, and by an antisense oligonucleotide to IGF-I. In turn, the effect of IGF-I is blocked by ICI 182,780 and by the antisense oligonucleotide to the estrogen receptor. These findings indicate that estrogen-induced activation of the estrogen receptor in developing hypothalamic neurons requires the presence of IGF-I and that both estradiol and IGF-I use the estrogen receptor to mediate their trophic effects on hypothalamic cells. In vivo, sex steroids affect IGF-I levels in the endocrine hypothalamus. IGF-I levels in tanycytes, a specific subtype of glial cells present in the arcuate nucleus and median eminence, are sexually dimorphic in the rat, increase with the onset of puberty, and are regulated by perinatal and adult levels of sex steroids. These changes may be due to hormonal modifications of IGF-I uptake by tanycytes from blood or cerebrospinal fluid. Therefore, this type of glial cell appears to play a central role in the interaction of sex steroids and IGF-I in the hypothalamus.

Animals↗