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  • 1
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Insulin-like growth factors I and II (IGFI and II) are synthesized by anterior pituitary cells and participate in cellular growth and differentiation, as well as the control of pituitary hormone secretion. Type 1 and 2 IGF receptors (IGFR1 and IGFR2) and the six IGF binding proteins (IGFBPs), which modulate IGF effects, are expressed in the anterior pituitary gland. We used in situ hybridization to analyse the temporal expression pattern of IGFI and II, IGFR1 and 2 and IGFBP1–6 in the anterior pituitary gland during postnatal development in both male and female rats (10, 20, 30, 40 and 60 days of age). We found all of the components of the IGF system to be expressed in the anterior pituitary gland, with each having a specific temporal pattern of expression. In addition, there exist differences between the sexes in the expression of some components of the IGF system. These data emphasize that in the anterior pituitary gland the IGF system is under tight regulation during postnatal life when this gland continues to develop. The distinct temporal expression of each member of the IGF system may indicate specific roles in the development and physiology of the anterior pituitary gland.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sex steroids and growth factors interact at the intracellular level in a variety of tissues to control numerous physiological functions. Oestrogen is known to stimulate prolactin synthesis and secretion, but the effect of insulin-like growth factor (IGF)-I is less clear. We used GH3 cells, a somatolactotroph cell line, to study the interaction of 17β-oestradiol (E2) and IGF-I on prolactin protein levels and the intracellular mechanisms involved. Cell cultures were treated with E2 (10 nM) and/or IGF-I (10 ng/ml) for 8 h. The real-time reverse transcriptase-polymerase chain reaction, Western blot and enzyme-immunoassay were used to determine changes in prolactin mRNA and protein levels. At this time-point, there were no significant changes in cell number, prolactin mRNA expression, or the amount of secreted prolactin. However, E2 increased intracellular prolactin concentrations. IGF-I alone had no effect, but blocked the stimulatory effect of E2. MAPK (ERK1/2) activation, as determined by Western blot analysis, increased with both E2 and IGF-I, but not with the combination of these factors. The MAPK inhibitor PD98059 blocked the ability of E2 to increase intracellular prolactin concentrations. Similarly, the IGF-I receptor antagonist, JB1, blocked the effect of E2 on prolactin synthesis and MAPK activation, as did the oestrogen receptor antagonist ICI182 780. These results suggest that, to stimulate prolactin synthesis, E2 activates the MAPK cascade and that this requires the presence of both oestrogen and IGF-I receptors.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    Journal of neuroendocrinology 14 (2002), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Undernutrition reduces circulating concentrations of insulin-like growth factor (IGF)-I, but how it affects the brain IGF system, especially during development, is largely unknown. We have studied IGF-I, IGF-II, IGF receptor and IGF binding protein (BP)-2 mRNA expression in the hypothalamus, cerebellum and cerebral cortex of neonatal rats that were food restricted beginning on gestational day 16. One group was refed starting on postnatal day 14. Rats were killed on postnatal day 8 or 22. Undernutrition did not produce an overall reduction in brain weight at either age but, at 22 days, both the cerebellum and hypothalamus weighed significantly less. At 8 days, no change was detected in the central IGF axis in response to undernutrition. However, in 22-day-old undernourished rats, IGF-I and IGF receptor mRNA expression were increased in both the hypothalamus and cerebellum, while IGFBP-2 was decreased, but only in the hypothalamus. Refeeding had no effect on any of these parameters. These results suggest that the hypothalamus and cerebellum respond to malnutrition and the decrease in circulating IGF-I, a peptide fundamental for growth and development, by increasing the local production of both the growth factor and its receptor in attempt to maintain normal development.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chronic systemic administration of growth hormone (GH)-releasing peptide-6 (GHRP-6), an agonist for the ghrelin receptor, to normal adult rats increases insulin-like growth factor (IGF)-I mRNA and phosphorylated Akt (pAkt) levels in various brain regions, including the hypothalamus. Because neuropeptide Y (NPY) neurones of the arcuate nucleus express receptors for ghrelin, we investigated whether these neurones increase their IGF-I and p-Akt levels in response to this agonist. In control rats, immunoreactive pAkt was practically undetectable; however, GHRP-6 increased p-Akt immunoreactivity in the arcuate nucleus, with a subset of neurones also being immunoreactive for NPY. Immunoreactivity for IGF-I was detected in NPY neurones in both experimental groups. To determine if activation of this intracellular pathway is involved in modulation of NPY synthesis RCA-6 cells, an embryonic rat hypothalamic neuronal cell line that expresses NPY was used. We found that GHRP-6 stimulates NPY and IGF-I mRNA synthesis and activates Akt in this cell line. Furthermore, inhibition of Akt activation by LY294002 treatment did not inhibit GHRP-6 induction of NPY or IGF-I synthesis. These results suggest that some of the effects of GHRP-6 may involve stimulation of local IGF-I production and Akt activation in NPY neurones in the arcuate nucleus. However, GHRP-6 stimulation of NPY production does not involve this second messenger pathway.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0888-7543
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-2965
    Keywords: Key words: Alkaline phosphatase – Anorexia nervosa – Bone remodeling – Carboxyterminal telopeptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Fragments derived from degradation of type I collagen C-telopeptide (CTX) can be nonisomerized (α) or β-isomerized (β) depending on the age of bone; i.e., mainly the α form is derived from new bone and the β 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 α- and β-CTX markers of bone resorption, the α/β ratio (α/β), 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 α- and β-CTX were significantly higher, in groups H and N than in group L. Bone AP correlated significantly with α-CTX (p= 0.0042) and α/β (0.0095) in the controls, but not with β-CTX, while in AN patients bAP correlated with β-CTX (p= 0.0000) and with α-CTX (p= 0.022) but not with the α/β 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 (β-CTX), while CTX found in healthy adolescent control females come from new bone (α-CTX). For this reason, α-CTX is more suitable than β-CTX for measuring bone resorption in controls and β-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.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0827
    Keywords: Key words: Bone mineral density — Insulin-dependent diabetes mellitus — Auxological parameters.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. 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× 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.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1076
    Keywords: Human chorionic gonadotropin ; Thalassaemia major ; Growth velocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of long-term human chorionic gonadotropin (HCG) therapy on the linear growth and biological growth parameters was studied in six thalassaemic boys aged 14.5–15.5 years old with hypogonadotropic hypogonadism. A significant (P〈0.001) increase in growth velocity (from 3.3±0.3 to 7.6±0.6 cm/year) was found after 6–12 months of therapy, without acceleration of bone age. A striking improvement in pubertal development was observed. The treatment significantly increased growth hormone (GH) response to l-dopa administration (P〈0.025) as well as sleep GH secretion (P〈0.025). Serum growth factors, evaluated as thymidine activity during deep sleep, increased (P〈0.001), but somatomedin C (Sm-C) levels did not. Prior to treatment, baseline and peak values of plasma growth hormone releasing hormone (GH-RH) following l-dopa were low. After HCG therapy, GH-RH response to l-dopa increased significantly (from 9.2±5.6 to 20.2±6.2 pg/ml; P〈0.05), but remained (P〈0.001) lower than in normal prepubertal children. This study suggests that in thalassaemia major an impaired GH-RH release can be observed, in addition to the described alteration in Sm-C generation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurology 241 (1994), S. 401-403 
    ISSN: 1432-1459
    Keywords: Herpes simplex ; Brainstem encephalitis ; Relapsing course ; Miller Fisher syndrome ; Landry-Guillain-Barré syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a patient with a relapsing form of acute brainstem encephalitis. Pathological examination demonstrated necrotizing encephalitis in the cerebral cortex and, more pronounced, throughout the diencephalon, as well as in the pcs pontis. Neurons and glial cells in the cerebral cortex and brainstem contained herpesvirus antigens. The clinical interrelationship of brainstem encephalitis, Miller Fisher syndrome and Landry-Guillain-Barré syndrome is discussed.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular neurobiology 16 (1996), S. 297-310 
    ISSN: 1573-6830
    Keywords: GH ; sexual dimorphism ; GHRH ; somatostatin ; neonatal steroid environment ; testosterone ; secretory pattern
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 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 neotatal 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.
    Type of Medium: Electronic Resource
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