Rapid decline of serum leptin levels in healthy neonates after birth.
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Adipose Tissue↗
Biomedical subjects
W Kiess
Publications and source records attributed to W Kiess.
[Which contraceptive methods are recommended for young women with type 1 diabetes mellitus? A survey among practitioners in Germany].
AIM: The aim of this study was to find out which recommendations German gynecologists gave to young patients with type 1 diabetes mellitus in respect to contraception. In addition, it was asked to what extent German gynecologists/obstetricians had experience regarding counselling of young women with type 1 diabetes. SUBJECTS AND METHODS: A structured questionnaire containing questions about attitudes, health care beliefs and contraception in young women with type 1 diabetes was developed. 804 attendees of the Giessen Gynecological Seminar which was held in January 1997 were asked to participate in the study. RESULTS: Only 142 (17.7%) of the questionnaires were returned. There was no consensus in respect to contraception in young women with diabetes. 61% of the respondents referred to the micropill (< 0.3 mg estrogen) as the preferred contraceptive method for young women with diabetes. Condoms were regarded as second line contraceptive devices in this age and patient group. There was only very limited experience in regard to counselling and treating adolescents/young women with type 1 diabetes. CONCLUSION: Among the German gynecologists questioned there was no consensus in respect to contraception in young women with diabetes. Most importantly, there was only very limited individual experience in regard to counselling and treating adolescents/young women with type 1 diabetes among the doctors who participated in the study.
Adolescent↗
Relation of leptin and neuropeptide Y in human blood and cerebrospinal fluid.
Leptin and neuropeptide Y (NPY) are involved in the regulation of food intake and body weight. Both hormones act through specific receptors in the central nervous system. The objective of this study was to investigate the relation of leptin and NPY in human plasma and cerebrospinal fluid (CSF). Leptin and NPY in CSF and in serum/plasma were measured by radioimmunoassays in 35 patients. Leptin concentrations in serum were 100-200 fold higher than in CSF. There was a significant correlation between leptin levels in CSF and in serum (r=0.88, P<0.0001). Female patients had significantly higher leptin serum concentrations than males (16.6+/-10.9 microg/l vs. 6.5+/-7.3 microg/l, P=0.002). In contrast, NPY levels were only twofold higher in CSF than in plasma. There was no relation between leptin and NPY in CSF and serum/plasma, respectively. The ratio of CSF and peripheral leptin levels did not correlate with the respective albumin ratio, indicating that leptin did not merely leak into the CSF via a defective blood-CSF barrier. It is concluded that leptin uptake from the circulation into CSF is a regulated process. The NPY concentration in CSF is not directly related to leptin CSF levels.
Female↗
Human neuroblastoma cells use either insulin-like growth factor-I or insulin-like growth factor-II in an autocrine pathway via the IGF-I receptor: variability of IGF, IGF binding protein (IGFBP) and IGF receptor gene expression and IGF and IGFBP secretion in human neuroblastoma cells in relation to cellular proliferation.
Neuroblastoma cells are thought to depend upon autocrine stimulation by IGF-II but not by IGF-I. We have studied the expression of IGF, IGFBP and IGF receptor mRNA in two human neuroblastoma cell lines, SK-N-MC and CHP, and asked whether or not the expression of the IGF system in these malignant cells determines their growth pattern. SK-N-MC cells grow with a cell doubling time of 36 hours in medium supplemented with 10% fetal calf serum whereas CHP cells only grow with a doubling time of 72 h. In addition, the SK-N-MC cell line has a plating efficiency ten times greater than the CHP cell line. RNase protection assays were performed using (32)P-labelled riboprobes and RNA that had been purified from SK-N-MC and CHP cells respectively. A 520 bases human IGF-I, a 556 bases human IGF-II, a 480 bases human IGF-I receptor and a 250 human IGF-II/mannose-6-phosphate (M6P) receptor probe were radiolabelled as were human IGFBP-1, -2, -3, -4, -5 and -6 probes. While both SKNMC and CHP neuroblastoma cells expressed mRNAs for IGFBP-2, -4, and -6 no signal was detected for IGFBP-1, and -3 and only SK-N-MC cells expressed IGFBP-5 mRNA. In addition, a 400 bases protected band was seen with the IGF-I receptor probe and a 260 bases protected band with the IGF-IIM6P receptor probe in either cell line. Interestingly, a 300 bases protected species was detected with the IGF-II probe in CHP cell RNA whereas SK-N-MC cells did not express IGF-II transcripts. Conversely, SK-N-MC cells expressed a 520 bases IGF-I transcript while CHP cells did not show IGF-I mRNA expression. As determined by specific radioimmunoassays SK-N-MC cells secreted 0.75+/-0.02 ng/ml IGF-I, 1.2+/-0.04 ng/ml IGF-II and 149+/-2.1 ng/ml IGFBP-2 within 24 h, whereas CHP cells secreted 0.1+/-0.01 ng/ml IGF-I, but 6.2+/-0.1ng/ml IGF-II and 254.8+/-5.5 ng/ml IGFBP-2 (N=5). IGFBP-2 secretion correlated positively with IGF-II secretion in CHP cells (r=0.85, P=0.05) and negatively with IGF-I (r= -0.9, P<0.01) in SK-N-MC cells. In conclusion, SK-N-MC cells which grow rapidly and have a high plating efficiency, express IGF-I, while CHP cells that grow more slowly express IGF-II. We hypothesize that neuroblastoma cells depend upon autocrine stimulation by either IGF-I or IGF-II. Variable sensitivity to growth inhibitors or apoptotic processes may be related to the differential expression of the IGF system.
Autocrine Communication↗
Developmental patterns of serum 3 alpha-androstanediol glucuronide.
3 alpha-androstanediol glucuronide (3 alpha diolG) is a marker of peripheral tissue androgen metabolism. There are no previous data regarding complete paediatric reference ranges for 3 alpha diolG. In order to obtain reference values for 3 alpha diolG we have measured serum levels of 3 alpha diolG in 283 healthy children and adolescents, 146 boys and 137 girls, age 1 month to 20 years and 28 adults. A non-extraction, solid phase radioimmunoassay employing a polyclonal antiserum that is specific for 3 alpha diolG was used to measure serum 3 alpha diolG levels (intra assay variation 5.1-10.1%, inter assay variation 2.7-9.0%). There was a strong sex and age dependence (r = 0.8; p < 0.0001) of 3 alpha diolG levels throughout childhood and adolescence with males showing significantly higher levels of the androgen than females (p < 0.05). 3 alpha diolG serum levels (nmol/l +/- SD) correlated significantly with pubertal stage (p < 0.01). Interestingly, in 35 children with CAH serum 3 alpha diolG levels correlated well with clinical and metabolic status, i.e. 17OHP serum levels. In summary, we have established percentile curves for 3 alpha diolG levels in healthy children and adolescents. We hypothesize that on the basis of our reference values the single measurement of serum 3 alpha diolG could serve as a means to determine androgen status in children with disorders of puberty and sexual development.
17-alpha-Hydroxyprogesterone↗
Developmental patterns of serum 3 alpha-androstanediol glucuronide.
3 alpha-androstanediol glucuronide (3 alpha diolG) is a marker of peripheral tissue androgen metabolism. There are no previous data regarding complete paediatric reference ranges for 3 alpha diolG. In order to obtain reference values for 3 alpha diolG we have measured serum levels of 3 alpha diolG in 283 healthy children and adolescents, 146 boys and 137 girls, age 1 month to 20 years and 28 adults. A non-extraction, solid phase radioimmunoassay employing a polyclonal antiserum that is specific for 3 alpha diolG was used to measure serum 3 alpha diolG levels (intra assay variation 5.1-10.1%, inter assay variation 2.7-9.0%). There was a strong sex and age dependence (r = 0.8; p < 0.0001) of 3 alpha diolG levels throughout childhood and adolescence with males showing significantly higher levels of the androgen than females (p < 0.05). 3 alpha diolG serum levels (nmol/l +/- SD) correlated significantly with pubertal stage (p < 0.01). Interestingly, in 35 children with CAH serum 3 alpha diolG levels correlated well with clinical and metabolic status, i.e. 17OHP serum levels. In summary, we have established percentile curves for 3 alpha diolG levels in healthy children and adolescents. We hypothesize that on the basis of our reference values the single measurement of serum 3 alpha diolG could serve as a means to determine androgen status in children with disorders of puberty and sexual development.
Adolescent↗
Expression of IGF receptors on alveolar macrophages: IGF-induced changes in InsPi formation, [Ca2+]i, and pHi.
Expression of insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose-6-phosphate (IGF-II/Man6P) receptors in cultured bovine alveolar macrophages (BAM) was demonstrated by competitive binding studies and crosslinking experiments. Western blotting of protein extracts from cultured BAM using an anti bovine IGF-II/Man6P receptor antiserum (#66416) confirmed the presence of IGF-II/Man6P receptors on BAM. The effects of IGFs and Man6P on generation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo-[3H]inositol-labelled cultured BAM. IGF-I at nanomolar concentrations and Man6P (10[-8]-10[-3] M) stimulated the accumulation of both Ins(1,4,5)P3 and Ins(1,3,4,5)P4 after 30 sec. IGF-II (up to 2.3 x 10[-8] M) had no significant effect on inositol phosphate accumulation under the same conditions. Both IGFs and Man6P induced a rise in [Ca2+]i in cultured BAM. In addition, using the fluorescent dye SNARF-1/AM we could demonstrate rapid but small IGF-II (10[-9] M) triggered acidification (0.07 pH units) of cultured BAM. Taken together, our results indicate not only the presence of both IGF-I and IGF-II/Man6P receptors on BAM, but also provide evidence of the linkage of the IGF-I receptor to the inositol phosphate system.
Animals↗
Decreased sensitivity to insulin-like growth factor I as a cause of growth failure in Turner's syndrome?
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Female↗
IGF-I, IGF-II, free IGF-I and IGFBP-1, -2 and -3 levels in venous cord blood: relationship to birthweight, length and gestational age in healthy newborns.
The insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBPs) have been implicated in regulating fetal growth and development. The aim of this study was to determine whether fetal IGFs correlate with auxologic data at birth and/or gestational age. Venous cord blood was obtained from 138 healthy newborns immediately after birth and clinical data were recorded using a standardized data sheet. For the determination of IGF-I and IGF-II, IGFBP-blocked radioimmunoassays were used. A coated-tube immunoradiometric assay was applied for the measurement of free IGF-I. IGFBP-1, -2, and -3 were measured using specific radioimmunoassays. IGF-I levels were 61 +/- 21 ng ml(-1), median 61 ng ml(-1), range 19-114 ng ml(-1); IGF-II levels were 466 +/- 80 ng ml(-1), median 457 ng ml(-1), range 311-701 ng ml(-1); free IGF-I levels were 2.4 +/- 1.8 ng ml(-1), median 1.8 ng ml(-1), range 0.4-7.8 ng ml(-1). The concentration of IGFBP-1 was 144 +/- 110 ng ml(-1), median 113 ng ml(-1), range 20-626 ng ml(-1); that of IGFBP-2 was 1165 +/- 455 ng ml(-1), median 1119 ng ml(-1), range 440-3466 ng ml(-1). IGFBP-3 levels were 1272 +/- 280 ng ml(-1), median 1272 ng ml(-1), range 600-1966 ng ml(-1). IGF-I levels correlated significantly with IGFBP-3 levels (r = 0.71), birthweight (r = 0.48) and birth length (r = 0.37). There were significant inverse correlations between IGF-I and both IGFBP-1 (r = -0.45) and IGFBP-2 (r = -0.62). Although free IGF-I levels correlated (r = 0.71) with total IGF-I, only marginally significant correlations were found between free IGF-I and birthweight (r = 0.25). According to multiple regression analysis free IGF-I levels were only dependent upon total IGF-I, IGFBP-2 and IGFBP-1, whereas IGFBP-3 levels did not contribute to the variance of free IGF-I concentrations in venous cord blood. There was no significant correlation between IGF-II and auxologic data at birth. When IGF-I and IGFBP-3 levels were analysed with respect to gestational age a biphasic pattern with maxima at 270 d was observed. IGFBP-2 exhibited a reversed pattern with a minimum at 265 d of gestation. In conclusion, these data suggest that IGF-I and the IGFBPs, but not IGF-II, play a role in the regulation of late fetal growth and development.
Birth Weight↗
Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight.
The mechanisms by which maternal and fetal weight are regulated during pregnancy are poorly understood. The ob protein, termed leptin, is produced by adipocytes. It is involved in the regulation of body weight by suppressing appetite and stimulating energy expenditure both in humans and rodents. In this study we examined whether leptin concentrations in the mother and the newborn correlate with birth weight, placental weight, and maternal weight at term. Leptin concentrations were measured in amniotic fluid, venous and arterial cord blood, and maternal serum at birth (n = 27) using a specific RIA employing human recombinant leptin for tracer and standard preparation. Gestational age was 38-42 weeks, maternal age was 21-42 yr, mean maternal weight at birth was 80.0 +/- 10.8 kg, and mean body mass index before pregnancy was 23.4 +/- 2.8 kg/m2. The newborns' mean weight was 3450 +/- 580 g, and mean placental weight was 616 +/- 120 g. Serum leptin levels from nonpregnant women ranged between 1.7-18.4 ng/mL, median 5.5 ng/ml (n = 30). Mean leptin concentration in maternal serum at birth was 20.0 +/- 13.2 ng/mL and was higher (P < 0.002) than in arterial cord blood (9.7 +/- 9.4 ng/mL) and venous cord blood (8.9 +/- 8.6 ng/mL). Mean amniotic fluid leptin concentration was 3.6 +/- 2.8 ng/mL. Placental weight correlated inversely with leptin levels in maternal serum at birth (r = -0.49, P < 0.01). In addition, leptin concentrations in venous cord blood correlated significantly with the levels in arterial cord blood (r = 0.98, P < 0.0001), and leptin levels in cord blood correlated positively with birth weight (r = 0.57, P = 0.03) and placental weight (r = 0.50, P < 0.01). In contrast, there was no correlation between maternal serum leptin levels and birth weight. Thus, leptin levels are high in the fetus and in the mother at term. We hypothesize that high leptin levels could represent an important feed-back modulator of substrate supply and subsequently for adipose tissue status during late gestation.
Amniotic Fluid↗
Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone.
Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis according to pubertal stage showed a steady increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further progression of puberty that was much less pronounced in girls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty and in adolescents. In boys, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels in a multiple regression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = a*e(b*BMI) and stratifying ranges according to gender and pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels increase in girls and decrease in boys after Tanner stage 2 as the pubertal development proceeds; 2) they show a significant gender difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.
Adipose Tissue↗
Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands.
We have identified and characterized insulin-like growth factor (IGF)-I and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in normal adult human adrenocortical tissue. Furthermore, we investigated the IGF-I receptor concentration and binding characteristics in benign and carcinomatous adrenocortical tumors. Membrane preparations of 14 normal adrenocortical glands showed a mean specific 125I-IGF-I binding (SB) of 5.0 +/- 0.5% and a competition by unlabeled ligands which is characteristic of the IGF-I receptor. The Scatchard analysis revealed a single class of high affinity binding sites with a dissociation constant (Kd) of 0.16 +/- 0.03 nmol/l, and a receptor concentration (RC) of 19.2 +/- 2.5 nmol/kg protein. Affinity cross-linking experiments with normal and tumorous adrenocortical tissue displayed a band at an apparent molecular mass of 135 kDa, corresponding to the size of the normal alpha-subunit of the IGF-I receptor. In agreement, 125I-IGF-II binding to normal adult human adrenocortical membranes was characteristic for the IGF-II/M6P receptor, and the Scatchard analysis revealed the presence of a single class of high affinity binding sites (SB 7.5 +/- 0.5%, RC 1137 +/- 265 nmol/kg protein, Kd 2.20 +/- 0.46 nmol/l, n = 6). The identity of the IGF-II/M6P receptor in adrenocortical tissue was further confirmed by Western blotting showing a specific band at 220 kDa. When 125I-IGF-I binding in adrenocortical hyperplasias (SB 4.1 +/- 0.4%, RC 19.6 +/- 2.0 nmol/kg protein, Kd 0.19 +/- 0.04 nmol/l, n = 4) and adenomas (SB 4.0 +/- 1.1%, RC 17.5 +/- 3.1 nmol/kg protein, Kd 0.21 +/- 0.04 nmol/l, n = 4) was compared with the 125I-IGF-I binding in normal adrenocortical tissue, similar IGF-I receptor concentration and binding kinetics were found. In contrast, three out of four hormonally active adrenocortical carcinomas showed a strongly elevated specific 125I-IGF-I binding with a 3- to 4-fold increase in IGF-I receptor concentration, as compared with normal adrenocortical tissue. This resulted in a significantly higher mean specific binding and receptor concentration in adrenocortical carcinomas, while the binding kinetics and the size of the alpha-subunit of the IGF-I receptor remained unaltered (n = 4, SB 13.8 +/- 4.2%, RC 72.2 +/- 21.3 nmol/kg protein, Kd 0.17 +/- 0.02 nmol/l). In summary, we show that intact IGF-I and IGF-II receptors are present in normal adult human adrenocortical tissue. While the abundance of the IGF-I receptor in adrenocortical hyperplasias and adenomas was similar to normal tissue, a strong overexpression of the intact IGF-I receptor was found in three out of four adrenocortical carcinomas.
Adenoma↗
Pertussis toxin sensitive G-proteins are not involved in the mitogenic signaling pathway of insulin-like growth factor-I in normal rat kidney epithelial (NRKE) cells.
There is controversy as to whether or not a pertussis toxin sensitive G-protein is involved in the signaling pathway of insulin-like growth factor-I. We have used normal rat kidney epithelial (NRKE) cells to ask whether or not a pertussis toxin sensitive G-protein was involved in IGF-I stimulated DNA synthesis. NRKE cells express both IGF and IGF-II/M6P receptors and respond to IGF-I with increased thymidine incorporation into DNA. Under many circumstances incubation of cells/cell membranes with GTP analogues will inhibit binding of ligands that are linked to a G-protein-receptor pathway. However, when NRKE membrane preparations were incubated with 125I-IGF-I or 125I-IGF-II in the presence or absence of GTP gamma S, ATP and GTP, binding of the radioligands was not affected by the GTP-analogue. IGF-I and factors from serum of hypophysectomized rats (HRS) stimulated [3H]thymidine incorporation into DNA of NRKE cells. Under serum-free conditions in the presence of EGF (2 ng/ml) and PDGF (1 ng/ml) pertussis toxin over a wide range of doses had no effect upon IGF-I stimulated [3H]thymidine incorporation into DNA of NRKE cells. In addition, PT at a dose of 100 ng/ml had no effect on IGF-I(0.2-50 ng/ml) stimulated DNA synthesis of NRKE cells. However, PT at doses of 5, 50, 500, 5000 and 50,000 ng/ml was capable to ADP-ribosylate a 40 kDa protein in NRKE cell plasma membrane preparations corresponding to known PT-sensitive G-proteins. We conclude, that (1) PT-sensitive G-proteins and both IGF-I and IGF-II/M6P receptors are present in NRKE cell plasma membrane preparations, and most importantly, that (2) PT-sensitive G-proteins are not involved in the mitogenic signaling pathway of IGF-I in NRKE cells.
Animals↗
Opposite regulation of IGF-I and IGF-I receptor mRNA and concomitant changes of GH receptor and IGF-II/M6P receptor mRNA in human IM-9 lymphoblasts.
Human IM-9 lymphoblasts synthesize IGF-I and express IGF-I receptors, IGF-II/M6P receptors and GH receptors. We have studied the regulation of mRNA expression of IGF-I, IGF-I receptors, IGF-II/M6P receptors and GH receptors in IM-9 cells upon serum-withdrawal and re-addition of serum. IM-9 cells were cultured in RPMI-1640 medium with or without serum for various periods of time. RNA was prepared using guanidinium thiocyanate and CsCl. Antisense riboprobes for human IGF-I, IGF-I receptor, IGF-II/M6P receptor, GH receptor and for comparison for human beta-actin were synthesized and labeled with 32P. Protected fragments of 379 bases and of 420 and 350 bases with the IGF-I receptor and with the IGF-I probe respectively and protected fragments of 670 bases and of 51 and 121 bases with the GH receptor and with the beta-actin probe were detected. For the human IGF-II/M6P receptor probe protected fragments of 260 bases were visualized in RNA samples. The amount of mRNA present in each lane (10 microgram total RNA) was determined by computed densitometry. The amount of IGF-mRNA expressed by IM-9 cells decreased rapidly (within two hours) and dramatically (more than 120%) after the withdrawal of serum and increased significantly (220%) after the re-addition of serum. This increase of IGF-I mRNA preceded the increase in cell number that was seen after 48 h of medium change. Conversely, the expression of IGF-I receptor mRNA and beta-actin mRNA increased by more than 250% after the withdrawal of serum within 2 and 8 h respectively, while GH receptor mRNA fell within 2-4 h. The expression of IGF-II/M6P receptor mRNA continued to increase throughout the duration of the cell culture experiment. We conclude that IGF-I and IGF-I receptor mRNAs are regulated in an opposite direction in serum-deprived IM-9 lymphoblasts. In addition, GH receptor mRNA expression parallels IGF-I mRNA expression.
Actins↗
Endocrine disorders in septo-optic dysplasia (De Morsier syndrome)--evaluation and follow up of 18 patients.
UNLABELLED: Septo-optic dysplasia (SOD) is characterized by hypoplasia of the optic nerve, various types of forebrain defects and hormonal deficiencies. We have studied the clinical and endocrinological characteristics of 18 such patients retrospectively to: (1) better define the endocrine abnormalities in children with SOD; and (2) to find approaches for the interdisciplinary long-term care of children with SOD. The children were seen at the Children's Hospital of the University of Munich from 1976 to 1992 (8 boys, 10 girls; age at initial presentation: 1 day-13 years of age, mean 1.9 years). Unilateral hypoplasia of the optic nerve was found in 7 cases, bilateral hypoplasia in 11. Sonographic, CCT or MRI yielded the following results: 4 of the patients had a cavum septum pellucidum, 3 patients had hypoplasia of the cerebellum, 1 aplasia of the corpus callosum and 1 aplasia of the fornix. An empty sella with or without an ectopic pituitary was seen in 4 cases. Height standard deviation score (SDS) at time of diagnosis was -4.0 to +0.4, mean -2.92. Endocrine deficiencies were present in all 11 patients who had undergone endocrinological investigations. Seven patients suffered from isolated growth hormone (GH) deficiency or multiple hypopituitarism. One had diabetes insipidus centralis, 2 had hypogonadotropic hypogonadism, 1 had hypothyroidism and 2 adrenal insufficiency. Hypothalamic testing was performed only in a subset of patients: in 5 of 11 children tested a thyrotropin releasing hormone (TRH test), in two out of nine a gonadotropin releasing hormone (GnRH) test, and in three out of six GH releasing hormone (GHRH) test yielded abnormal results. High prolactin levels were measured in two out of five patients. CONCLUSION: SOD is characterized by optic nerve hypoplasia and a variety of endocrine deficiencies. In addition, forebrain malformations are present in most SOD patients. Hormonal disorders are present in some SOD patients which may be of hypothalamic origin and need to be investigated systematically.
Adolescent↗
Leptin concentrations in amniotic fluid, venous and arterial cord blood and maternal serum: high leptin synthesis in the fetus and inverse correlation with placental weight.
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Adult↗
High leptin concentrations in serum of very obese children are further stimulated by dexamethasone.
Serum leptin concentrations and the levels of ob mRNA in adipocytes in obese humans are elevated. Hyperphagia and obesity are characteristics of hypercortisolism. We have therefore asked whether or not leptin levels were elevated in very obese children, and whether or not dexamethasone would increase leptin levels in obese children. A single dose dexamethasone suppression test was performed in ten obese children (5 girls, 5 boys; age 6 to 16 yrs, mean 12 +/- 1, median 12 yrs) to rule out hypercortisolism. Body mass index (BMI) in the ten children was calculated to be 27-45 kg/m2. Venous blood was sampled before dexamethasone was given in the evening and at 9.00 a.m. the following morning. Endogenous cortisol production was suppressed in all patients. Leptin levels, as measured by a newly developed specific radioimmunoassay, were 31.6 +/- 12.9 microg/l, range 19.2-59.9 microg/l before dexamethasone and 39.9 +/- 16.5 microg/l, range 26.3-80.3 microg/l after dexamethasone in the obese children (ANOVA, p = 0.01). Simple regression analysis revealed that serum levels correlated significantly with body mass index (r = 0.82, p < 0.001). Non-obese children (BMI < 27 kg/m2) had leptin levels between 0.1 and 33.3 microg/l, median 2.2 microg/l (N = 713). Girls (5.5 +/- 4.6 microg/l) (N = 401) had significantly higher leptin levels than boys (1.7 +/- 2.1 microg/l (N = 312) (p < 0.0001). We conclude that 1) high serum leptin concentrations are present in obese children. 2) A single dose of dexamethasone significantly increases the high leptin serum levels in these children. We hypothesize that glucocorticosteroids up-regulate leptin levels in the human.
Adolescent↗
Expression of IGFBP-2, -3, and -4 mRNA during differentiation of Caco-2 colon epithelial cells.
Local production of insulin-like growth factor (IGF)-binding proteins (IGFBP) determines the availability of the IGF to the cell and thus regulates IGF action. To find out whether specific patterns of IGFBP gene expression and IGFBP secretion were related to cell growth vs. cell differentiation, expression of IGFBP during long-term culture (21 days, n = 5) of the colon carcinoma cell line Caco-2 was investigated at the mRNA and protein levels. Markers of cell proliferation (increase in DNA, RNA, and protein content) and of differentiation [alkaline phosphatase (AP) activity; creatine kinase (CK) activity] were measured in parallel during long-term culture. IGFBP-2 mRNA expression correlated significantly with markers of proliferation (P < 0.05), whereas IGFBP-3 mRNA expression or IGFBP-3 secretion correlated with markers of differentiation (AP: r = 0.83, P < 0.001; CK: r = 0.45, P < 0.01). Similarly, IGFBP-4 mRNA expression correlated significantly with markers of differentiation (AP: r = 0.34, P < 0.05; CK: r = 0.35, P < 0.05). We hypothesize that IGFBP-3 and -4 are related to differentiation of Caco-2 cells, whereas IGFBP-2 is related to proliferation in Caco-2 cells.
Alkaline Phosphatase↗