bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum vitamin D metabolites and calcitriol receptor concentration in parathyroid tissue in primary hyperparathyroidism
Authors: Trydal Torleif , Varhaug Jan Erik , Myking Andreas , Aksnes Lage , Aakvaag Asbjørn , Aarskog Dagfinn
Published: June 2009

Vitamin D metabolites in serum and calcitriol receptor concentration in parathyroid tissue were examined in 52 patients operated on for primary hyperparathyroidism. The calcitriol receptor levels were not different in parathyroid adenomas (mean 224 fmol/mg of protein, range 29–509, N = 43), normal parathyroid tissue (mean 245, range 31–690, N = 20), and primary parathyroid hyperplasia (mean 172, range 46–477, N = 9). Preoperative serum levels of calcitriol concentration correlated inversely to the calcitriol receptor in normal parathyroid tissue in patients with adenoma (r= −0.57, N=17, p=0.017), but no such correlation was found in the corresponding adenomas (r=0.14, p = 0.59). In 31 patients in whom both pre- and post-operative vitamin D metabolite analyses were carried out, 23 had lower calcitriol postoperative concentrations compared to preoperative values (p = 0.012, sign test). No change was found in the other vitamin D metabolites postoperatively. By multiple regression analysis calcitriol concentration in serum was inversely correlated to the serum concentration of urea and phosphate (p = 0.003). We conclude that calcitriol may influence calcitriol receptor expression in normal parathyroid tissue, but not in adenomatous parathyroid gland. Furthermore, serum calcitriol was correlated to the renal function, and phosphate level, and in most patients the calcitriol concentration was lower after the operation.
Effect of dopamine injection into the anteroventral third ventricular region and the paraventricular nucleus on vasopressin secretion in conscious rats
Authors: Yamaguchi Ken'ichi , Hama Hitoshi , Watanabe Kazuo , Adachi Chieko
Published: June 2009

To investigate the role of dopamine receptors situated in the paraventricular nucleus and the anteroventral third ventricular region in regulating vasopressin release, responses of plasma AVP and its controlling factors to injections of dopamine into these regions and the lateral cerebral ventricle were examined in conscious rats. The injections of 156 nmol (30 μg) dopamine into the cerebral ventricle produced transient rises in plasma AVP 5 min later. When the dose of dopamine was reduced to 26 nmol (5 μg), the increase in plasma AVP was not provoked any more. However, injections of 26 nmol dopamine into the paraventricular nucleus greatly augmented plasma AVP 5 and 15 min later. This dose of dopamine was without effect on plasma AVP when injected into the anteroventral third ventricular region, including the organum vasculosum lamina terminalis, median preoptic nucleus, medial preoptic area and the periventricular preoptic nucleus. These dopamine administrations in the cerebral ventricle, paraventricular nucleus and the anteroventral third ventricular region did not significantly change AVP-controlling factors such as plasma osmolality, sodium and arterial pressure. On the basis of these results, we conclude that dopamine receptors in the paraventricular nucleus may function to facilitate AVP secretion, whereas those in the anteroventral third ventricular region may not play an important role in the regulation of AVP release.
Re-expression of thyroxine-binding globulin in post-weaning rats during protein or energy malnutrition
Authors: Rouaze-Romet Marielle , Savu Lia , Vranckx Roger , Bleiberg-Daniel Fanny , Le Moullac Béatrice , Gouache Patricia , Nunez Emmanuel A
Published: June 2009

Thyroxine-binding globulin, the highest affinity thyroid hormone binder of rat serum, was studied during 28 days of dietary protein restriction (6% protein vs 18% protein in isocaloric control diet) or energy restriction (60% intake of control diet). Studies were performed on male rats aged four weeks at the beginning of experiments: the animals had reached the ontogenic stage when the thyroxine-binding globulin had declined, after its high postnatal surge, to undetectable levels. Short-term administration (seven days) of one or the other restricted diet similarly induced resynthesis of the protein. Its serum concentrations reached 26–46% of those measured in eight-day pups (peak of the neonatal surge) and its liver mRNAs showed corresponding enhanced signals. Serum T4 binding activities were increased, although concomitantly transthyretin, second specific T4 carrier of the rat serum, decreased markedly (65–75% of controls) in response to the dietary restrictions. Longer-term diet administration (14 or 28 days) resulted in the further increase of the thyroxine-binding globulin in the protein-restricted rats, in contrast to its decline and eventual disappearance in the energy-restricted animals. Protein restriction was associated with increased total and free T3 serum concentrations, in contrast to energy restriction which little affected these parameters. These studies reveal rat thyroxine-binding globulin as a positive (increasing), highly sensitive reactant of malnutrition, able to discriminate between energy deficiency and composition dysequilibrium of diets. They suggest that up-regulation of its synthesis in the two dietary models involves differential mechanisms.
Effects of ketoconazole on the iodide uptake by FRTL-5 cells
Authors: Kohan Sergio L , Guillén Carlota E , Pardes Esther M , Junco Marcelo , Soto Roberto J , Sartorio Gerardo C
Published: June 2009

Ketoconazole is an imidazole derivative used as an antimycotic agent with reported effects on the endocrine system, but very little is known about its possible actions on thyroid function. Our purpose was to study the influence of this substance on the basal and TSH-stimulated iodide uptake in the rat thyroid cell strain FRTL-5. Ketoconazole (1–50 μmol/l) was shown to slightly increase the basal iodide uptake but, at higher concentrations (75–100 μmol/l), it sharply decreased iodide uptake below the basal levels. When the cells were cultured under bTSH stimulation (30 UI/l), the inhibitory effect of ketoconazole was exerted at concentrations as low as 25 μmol/l. This inhibition was observed even if it was added to the culture medium immediately before the Na125I addition. Forskolin, a stimulator of adenylate cyclase activity, was unable to prevent the iodide uptake inhibition. Low doses of ketoconazole increased cAMP concentrations. In the presence of TSH this effect was more evident in an inverse dose-dependent way. Because of its dual action, it can be assumed that ketoconazole could influence the iodide uptake in the FRTL-5 cells through more than one mechanism.
Development of gonadal feedback regulation of gonadotropin gene expression and secretion in female rats
Authors: Pakarinen Pirjo A , Huhtaniemi Ilpo T
Published: June 2009

The postnatal development of the gonadal negative feedback control of gonadotropins was studied in female rats. Neonatal (5-day-old) and randomly cycling young (60-day-old) and more mature (180-day-old) adult rats were ovariectomized, and half of them received Silastic implants containing the synthetic estrogen, diethylstilbestrol. The neonatal rats were killed 5, 10 or 15 days, and the adult rats 7 days after the operation. Age-matched and sham-operated animals served as controls. There were no statistically significant responses of serum LH or FSH concentrations or of the pituitary gonadotropin subunit mRNA levels to ovariectomy at any of the neonatal ages. A marked increase (p<0.01) after ovariectomy was seen in serum gonadotropins and in the cognate mRNA levels at both adult ages. In spite of the weak feedback response of the neonatal rats to ovariectomy, diethylstilbestrol suppressed the basal pituitary gonadotropin concentrations and the specific LH and FSH β-chain mRNAs (p<0.01–0.05). These results demonstrate that the gonadal negative feedback regulation of gonadotropin synthesis and secretion is not fully developed in neonatal and prepubertal female rats before 20 days of age. This is probably due to the steroidogenic quiescence of the ovaries in early life. However, the capability of the pituitary to respond to negative estrogen feedback has developed in the neonatal female, as demonstrated by the suppressive effects of diethylstilbestrol treatment on gonadotropin secretion.
Effect of adenosine analogues on plasma corticosterone concentration in rats
Authors: Przegaliński Edmund , Budziszewska Bogusława , Grochmal Anna
Published: June 2009

In this study we examined the effect of the adenosine analogues: N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine and 5′-N-ethylcarboxamidoadenosine on the plasma corticosterone concentration in rats. It was found that N6-cyclohexyladenosine (0.1–3.0 mg/kg), L-N6-phenylisopropyladenosine (0.1–1.0 mg/kg) and 5′-N-ethylcarboxamidoadenosine (0.01–1.0 mg/kg) dose-dependently increased the plasma corticosterone level. The effects of N6-cyclohexyladenosine (0.1 mg/kg) and L-N6-phenylisopropyladenosine (0.1 mg/kg) were completely blocked in animals pretreated with dexamethasone (3 × 1 mg/kg), as well as in animals with a pharmacological blockade of the release of hypothalamic corticotropin-releasing factor induced by chloropromazine (10 mg/kg), morphine (20 mg/kg) and nembutal (25 mg/kg), whereas the corticosterone response to 5′-N-ethylcarboxamidoadenosine (0.01 mg/kg) was blocked in dexamethasone-pretreated rats only. On the other hand, the adenosine receptor antagonists: 8-(p-sulfophenyl)-theophylline (30 mg/kg), 8-phenyltheophylline (10 and 30mg/kg), 1,3-dipropyl-8-(2-amino-4-chloro)-phenylxanthine (1 and 3 mg/kg) and 1,3-dipropyl-7-methylxanthine (1 mg/kg) did not affect the corticosterone response to N6-cyclohexyladenosine, L-N6-phenylisopropyladenosine or 5′-N-ethylcarboxamidoadenosine. The obtained results indicate that N6-cyclohexyladenosine and L-N6-phenylisopropyladenosine stimulate the corticosterone secretion at the hypothalamic level, whereas 5′-N-ethylcarboxamidoadenosine is likely to act at the pituitary level. Although the effects produced by the adenosine analogues show that both A1 and A2 receptors are involved in the corticosterone response, negative results of the interaction studies with adenosine receptor antagonists indicate that further experiments are necessary to elucidate this problem.
Malignant prolactinoma
Authors: Berezin M , Gutman I , Tadmor R , Horowitz A , Findler G
Published: June 2009

Malignant prolactinoma is a rare entity and only a few cases have been published. The diagnostic criteria and the clinical course remain unclear. We present a case of malignant prolactinoma in a woman with a 30-year duration of the disease. In the terminal stage of the disease the prolactinoma metastasized to the left eye, the prolactin level reaching 196000 mU/l, Bromocriptine in high doses was not effective. The response to pergolide was good in the first two years of treatment; thereafter an escape effect was observed. The patient died in a comatose state. A review of previously published cases follows.
Progesterone increases basal 3′,5′-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in human term placenta
Authors: Rivera Jose , Bernal Andres Lopez , Cano Antonio
Published: June 2009

Whether the placenta is a target tissue for estrogens and progesterone, and their putative mechanism of action, is still a controversial question in the literature. The effect of progesterone and estradiol on 3′,5′-cyclic adenosine monophosphate (cAMP) and inositol phosphates generation in human term placenta was investigated. Placental explants were incubated in vitro for up to 48 h in the absence and in the presence of estradiol, progesterone or both steroids (0.1 μmol/l final concentration in all cases), and were stimulated with terbutaline, a β-adrenergic agonist, (0.1 mmol/l) or angiotensin II(1 μmol/l), The cAMP content was measured by a competitive protein binding assay, and the generation of labelled inositol phosphates formation in explants prelabelled with 3H-myo-inositol was measured by anion exchange chromatography. Progesterone increased significantly basal cAMP concentrations in comparison with control or estradiol-treated tissues (169±13, 72±8, and 69±2 pmol/g wet wt tissue, mean±sem, respectively). However, following terbutaline stimulation cAMP levels (mean±sem) increased to similar values under all conditions (182±33, 197±36, and 237±17 pmol/g wet wt tissue for control, estradiol-, and progesterone-treated tissues, respectively). Angiotensin II stimulated inositol phosphates generation in placental explants by an average of fivefold, but this increase was significantly reduced in the presence of progesterone (5.2±0.7, 3.7±0.4, and 2.2±0.3 fold increase vs non-angiotensin-stimulated tissues, for control, estradiol-, and progesterone-treated placenta, mean±sem, respectively). These data suggest that progesterone modulates the formation of second messengers in human placenta at term.
Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism
Authors: Giustina Andrea , Bussi Anna Rosa , Legati Fabio , Bossoni Simonetta , Licini Massimo , Schettino Maurizio , Zuccato Fausto , Wehrenberg William B
Published: June 2009

Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25–50 years) and six healthy volunteers (3F, 3M, aged 27–76 years) underwent from - 10 to 30 min in random order: (i) porcine galanin, iv, 500 μg in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 μg, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2±2.5 μg/l) compared to normal subjects (20.7±4.8 μg/l, p< 0.05). GH peaks after GHRH+ galanin were also significantly lower in hyperthyroid subjects (12.5±3 μg/l) compared to normal subjects (43.8±6 μg/l, p<0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.
Catecholamines stimulate testicular testosterone release of the immature golden hamster via interaction with alpha- and beta-adrenergic receptors
Authors: Mayerhofer A , Steger RW , Gow G , Bartke A
Published: June 2009

Several lines of evidence suggest that catecholamines are involved in the regulation of the development of the testis. We have therefore investigated the ability of testicular parenchyma (decapsulated pieces of testes) from 18 to 20-day-old golden hamsters to respond to catecholaminergic stimuli in vitro. Norepinephrine and epinephrine, as well as the beta-receptor agonist isoproterenol and the alpha-adrenoreceptor agonist phenylephrine were able to significantly stimulate testicular testosterone production. Dopamine and serotonin were not effective. The stimulatory action of norepinephrine on testosterone production was dependent on the concentration. In incubations of testes with human chorionic gonadotropin (hCG) and norepinephrine, no synergistic effects on testosterone release were observed. The stimulatory effect of norepinephrine could be partially blocked by incubation with beta-receptor antagonist propranolol, or with alpha-receptor antagonist prazosin, while a combination of propranolol and prazosin completely inhibited the norepinephrine-induced testosterone production. Moreover, isoproterenol and phenylephrine in combination stimulated testosterone more than either drug did alone. Measurements of concentrations of norepinephrine and epinephrine in testicular homogenates revealed higher values for these catecholamines than in the plasma, implying that catecholamine levels in the interstitial spaces of the testis might be in the range of concentrations effectively stimulating testosterone production in vitro. This suggests that in the immature testis of the golden hamster, catecholamines acting through both alpha- and beta-adrenergic receptors may be potent physiological stimulators of testosterone production.
Growth hormone secretion in old female rats analyzed by the reverse hemolytic plaque assay
Authors: Takahashi Sumio
Published: June 2009

Growth hormone (GH) release was studied in young (3–4-month-old) and old persistent diestrous (20– 21-month-old) female rats using the reverse hemolytic plaque assay. A bimodal distribution of reverse hemolytic plaque area was observed in both young and old female rats. The mean and median of the plaque area of GH cells from old females were smaller than those from young female rats. The percentage of plaque-forming GH cells in old female rats was lower than in young female rats. The percentage of large plaque-forming GH cells (plaque area, more than 8 × 103 μm2) was lower in old female rats than in young female rats. GH-releasing hormone (GHRH) increased the mean and median of plaque areas in both young and old female rats. However, responsiveness to GHRH was reduced in old female rats. These results indicate that the amount of GH released from individual GH cells decreases with age in female rats, resulting in diminished GH secretion.
Studies on the rapid stimulation of mitochondrial respiration by thyroid hormones
Authors: O'Reilly Ian , Murphy Michael P
Published: June 2009

Injection of L-3,5-diiodothyronine (T2) into rats made hypothyroid by 6-n-propyl-2-thiouracil (PTU) increased the respiration rates of subsequently isolated liver mitochondria; this stimulation of respiration by T2 occurred in the presence of cycloheximide and is therefore independent of protein synthesis on cytoplasmic ribosomes. Injection of T3 into PTU-treated rats had a lesser effect than T2 on the respiration rates of subsequently isolated mitochondria; as PTU is an inhibitor of 5′-iodothyronine deiodinases, which convert T3 into T2 in vivo, the rapid stimulation of mitochondrial respiration by T3, which has been shown in a range of systems, may not be due directly to T3 itself, but may be mediated by its deiodination product T2. Injection of T2, or T3, into hypothyroid or euthyroid rats had no effect on the percentage activity of mitochondrial pyruvate hydrogenase assayed 30 min later. The amount of active pyruvate dehydrogenase is regulated by changes in mitochondrial calcium concentration and matrix ATP/ADP ratio; therefore these parameters are not persistently affected by treatment with T3 or T2. In addition, the total amount of pyruvate dehydrogenase present was the same in euthyroid and hypothyroid rats, indicating that the expression of this enzyme is not stringently controlled by thyroid hormone status.
Effects of chronic thyroid hormone administration on pregnancy, lactogenesis and lactation in the rat
Authors: Rosato Roberto R , Gimenez Maria S , Jahn Graciela A
Published: June 2009

We studied the effects of daily administration of 1 mg/kg thyroxine (T4) starting 10–15 days before mating, on parturition, maternal behavior and lactation in rats. Treated rats had elevated serum titers of T3 and T4, a greater number of fetuses and parturition was advanced approximately 12 h and lasted longer than in controls. None of the treated rats were able to lactate because of defects in maternal behavior and milk ejection; the litters died usually within 48 h postpartum. In rats sacrificed at 10.00 on day 21 of pregnancy, mammary gland content of total protein, phospholipids, casein and lactose were significantly increased, but total lipid was markedly reduced. Lipogenesis was also significantly increased, as well as the activity of the lipogenic enzymes glucose-6-phosphate dehydrogenase, fatty acid synthetase and isocytrate dehydrogenase. These results are indicative of normal albeit premature lactogenesis. The T4-treated rats also had advances in the prepartum fall in serum progesterone and the increase in prolactin as well as in the increase in mammary casein and lactose concentrations of approximately 12 h with respect to control pregnant rats. These results show that chronic T4 treatment induces an advance of approximately 12 h in luteolysis, which in turn advances lactogenesis and parturition in rats. Although the mammary gland was able to produce milk, lactation failed due to abnormal maternal behavior and milk ejection, the causes of which are still unknown. Other effects of hyperthyroidism were also present, such as a severe reduction in lipid content of the gland. The observed increases in lipogenesis and lipogenic enzyme activities could be due to a combination of the effects of hyperthyroidism per se as well as to the increase in lipogenesis that occurs during lactogenesis.
The effect of growth hormone administration on testicular response during gonadotropin therapy in subjects with combined gonadotropin and growth hormone deficiencies
Authors: Balducci Rina , Toscano Vincenzo , Mangiantini Adele , Bianchi Patrizia , Guglielmi Rinaldo , Boscherini Brunetto
Published: June 2009

To evaluate the effect of growth hormone on testicular response to human chorionic gonadotropins (hCG) in vivo in humans, we selected patients with combined deficits of GH and gonadotropins who were in substitution treatment with both GH (from the time of diagnosis) and gonadotropins (from the time of induction of puberty). Testicular response to gonadotropin therapy was then evaluated during and six months after the cessation of GH treatment. Blood samples were collected before and 2, 4 and 6 days after hCG administration. hCG responses were calculated and expressed as the areas under the response curve. We studied four hypogonadotropic patients (aged 18–19 years) with associated GH deficiency. Their gonadotropin treatment consisted of hCG 1500IU every six days, and FSH 75 IU every three days. The GH therapy replacement consisted of 4 IU thrice weekly. Testosterone, androstenedione, 17α-hydroxyprogesterone and estradiol were measured. In all subjects the testosterone area during GH treatment was significantly higher compared to the testosterone area obtained without GH administration (2993±1091 vs 2310±751; M±sd; p<0.04). The androstenedione area followed a similar pattern (708±377 vs 402±248; M±sd; p<0.05). The 17α-hydroxyprogesterone area, on the contrary, was significantly higher during GH withdrawal (542±307 vs 235±190; M±sd; p<0.05). As far as the estradiol area is concerned, no significant differences were found (22860±10082 vs 25697±13640; M±sd). In conclusion, GH administration seems to improve testosterone production induced by human chorionic gonadotropins. The finding of the inverse response pattern of 17α-hydroxyprogesterone with respect to testosterone led us to suppose that the increased testosterone area during GH treatment may be due to an increased activity of C17,20-lyase enzyme.
Urinary excretion of GH in healthy individuals and patients with acromegaly, hypopituitarism and dwarfism
Authors: Quade Annegret , Rahn Michael , Schweikert Hans-Udo , Bidlingmaier Frank , Klingmüller Dietrich
Published: June 2009

Urinary GH excretion reflects average plasma levels. Using a highly sensitive sandwich enzyme immunoassay we determined GH concentrations in the 24 h accumulated urine samples of 54 healthy persons (aged 1.5–90 years), 8 acromegalic patients, 4 acromegalic patients after enucleation of a GH-producing adenoma, 8 patients with partial hypopituitarism and in first morning urine and 12 h accumulated daytime urine of 4 healthy children and 3 children with growth failure. GH secretion is age-dependent, with high rates between ages 1 and 20 (ages 0–20 years: 10.4 ng/g creatinine±6.3 vs age > 20–75 years: 3.1 ng/g creatinine±1.6). An age-dependent increase in urinary GH is found in the pubertal age group (10 ng/24 h±6.8 vs prepubertal group: 4.6 ng/24 h±2.95). GH excretion of patients with acromegaly differs significantly from healthy subjects (72 ng/24 h±49 vs 3.9 ng/24 h±2.3). After a successful operation, acromegalic patients do not differ from the collective norm. Six of 8 patients with partial hypopituitarism show lower GH concentrations in urine than healthy subjects (1.2 ng/l±0.2 vs 2.6 ng/l±1.2), but daily GH output does not differ, since significantly more urine is then excreted. At night, healthy children secrete significantly more GH than during the day (night: 0.16 ng·kg−1·(12 h)−1±0.02 vs day: 0.07 ng·kg−1·(12 h)−1±0.03), while output is the same for GH-deficient children. Both groups have similar GH daytime output, but GH-deficient children have significantly less nocturnal output. In conclusion, measuring urinary GH excretion seems to be a suitable means of diagnosing GH hypo- and hypersecretion.
Influence of smoking and snuff use on electrolytes, adrenal and calcium regulating hormones
Authors: Eliasson Mats , Hägg Erik , Lundblad Dan , Karlsson Roger , Bucht Elisabet
Published: June 2009

Little is known about the effects of snuff use on health. We have investigated electrolyte levels, adrenocortical and calcium regulating hormones in three groups of healthy young men, including 18 non-tobacco users, 21 snuff users and 19 smokers with similar age and body mass index. Smoking and snuff use was positively associated with alcohol and coffee consumption and inversely related to physical activity. Compared to non-tobacco users, smokers had significantly increased levels of serum sodium and magnesium, plasma calcitonin, urinary cortisol and potassium levels and decreased serum sex hormone-binding globulin as well as serum and urinary creatinine values. However, only decreased sexual hormone-binding globulin and urinary creatinine and increased serum phosphate and urinary potassium levels were seen in snuff users. Among tobacco users we noted that smokers differed from snuff users in that they had higher serum sodium (1.4mmol/l, p<0.01), plasma calcitonin (3.3 pmol/l, p<0.05) and urinary cortisol (41 nmol/24 h, p<0.05) but lower serum creatinine (5.8 μmol/l, p <0.01). We conclude that chronic snuff use appears to have less influence on hormone and electrolyte balance than does smoking, and that some of the abnormalities seen in smokers do not seem to be mediated by nicotine.
Glucocorticoids modulate the synthesis and expression of a 72 kDa heat shock protein in cultured Graves' retroocular fibroblasts
Authors: Heufelder Armin E , Wenzel Bjoern E , Bahn Rebecca S
Published: June 2009

Glucocorticoids modulate numerous proliferative, metabolic and immunological functions in human fibroblasts, some of which appear to be mediated via glucocorticoid receptors. We studied the influence of glucocorticosteroids on the synthesis and expression of a 72 kDa heat shock protein that is thought to play a role in thyroid autoimmunity. Experiments were performed using orbital fibroblasts derived from patients with Graves' ophthalmopathy and normal individuals. Cell monolayers were exposed to various concentrations of dexamethasone, the specific glucocorticoid agonist RU 28362, the glucocorticoid antagonist RU 38486, or combinations thereof, prior to heat stress or exposure to hydrogen peroxide. Heat shock protein 72 expression was assessed using sodium dodecylsulfate polyacrylamide-gel electrophoresis of cellular extracts, followed by autoradiography or immunoblotting with a mouse monoclonal antibody against the 72 kDa heat shock protein and quantitative scanning densitometry. In addition, cellular distribution of the immunoreactivity for the 72 kDa heat shock protein was studied using indirect immunofluorescence on parallel cultures. In other experiments, aimed at studying heat shock protein synthesis, cell cultures were pulse-labeled with [35S]-methionine prior to harvesting. Treatment with dexamethasone or RU 28362 markedly attenuated the heat stress-enhanced synthesis and expression of the 72 kDa heat shock protein and several other heat shock proteins both in normal and in Graves' retroocular fibroblasts (p<0.001). In addition, either treatment reduced baseline expression of the 72 kDa heat shock protein in Graves' retroocular fibroblasts (p<0.01). These effects were dose-dependent and appeared to be mediated via the glucocorticoid receptor, because combined exposure to dexamethasone or RU 28362 plus RU 38486 completely restored synthesis and expression of the 72 kDa heat shock protein. Baseline or stress-enhanced expression of the 72 kDa heat shock protein was not altered by treatment of monolayers with RU 38486 alone. As demonstrated by immunofluorescence, the characteristic intracellular shifting of the 72 kDa heat shock protein in response to cellular stress was partially inhibited by glucocorticoid agonists and restored by simultaneous exposure to glucocorticoid agonists and RU 38486. These results demonstrate that dexamethasone and the specific glucocorticoid agonist RU 28362 can modulate baseline- and stress-induced synthesis and expression of the 72 kDa heat shock protein, as well as its subcellular distribution. in cultured retroocular fibroblasts. Our studies suggest that these compounds exert these effects via the glucocorticoid receptor.
Long-term follow-up in patients with autonomous thyroid adenoma
Authors: Sandrock D , Olbricht T , Emrich D , Benker G , Reinwein D
Published: June 2009

A group of 375 untreated euthyroid patients with solitary autonomous adenoma of the thyroid were studied in a long-term follow-up (observation period 52.8 (mean)/46 (median), range 3–204 months). During the period of observation, 133 (34.2%) of all initially untreated patients underwent treatment (surgery, radioiodine, antithyroid medication) because of hyperthyroidism, mechanical problems, or at the patient's request. Sixty-seven patients developed hyperthyroidism resulting in a mean incidence of 4.1% per year. The incidence of hyperthyroidism increased during follow-up (3% in the first seven years, 10% in the following years). Age, sex, nodule size, initial scintigraphic appearance and the TRH test were of no individual prognostic value in predicting hyperthyroidism. Eleven of 14 patients with untreated hyperthyroidism became euthyroid without treatment during the time of follow-up. After iodine excess (by history or elevated iodine levels in urine, N=45), 14 patients (31%) developed hyperthyroidism. In conclusion, we recommend a definitive treatment of autonomous adenoma at least in patients with advanced age, concomitant diseases and a higher probability of iodine exposure.
Insulin-like growth factor I accelerates proliferation and differentiation of cartilage progenitor cells in cultures of neonatal mandibular condyles
Authors: Maor Gila , Hochberg Zeev , Silbermann Michael
Published: June 2009

The present study examined the effect of exogenous IGF-I on growth and development of neonatal cartilage of the mandible condyle. Condylar cartilage was cultured as organ culture. The explants were cultured on top of collagen sponges in medium containing 2% fetal calf serum and were treated with IGF-I at doses ranging from 3.25 to 26 nmol/l for up to six days. IGF-I was found to increase significantly the uptake of [3H]-thymidine and [35S]-sulfatein a dose-related manner. The enhanced cellular proliferation, along with the increased synthesis of proteoglycans, resulted in a substantially larger mass of tissue in the organ culture system. The nature of the IGF-I stimulative effect was further studied through the use of a tissue culture system whereby a separated chondroprogenitor zone is cultured under conditions which favor its development at first into cartilage and then into bone. Using this culture system, we could show that IGF-I induces merely the de novo chondrogenesis process. This was reflected in the appearance of relatively large amounts of cartilage specific antigens such as type II collagen, cartilage proteoglycans, chondrocalcin and 100 KDa protein. Yet, no bone specific antigens were significantly increased, as is the case with GH effects. These results indicate that IGF-I is a strong chondrogenetic agent. But, unlike growth hormone, it does not seem to stimulate bone formation.
Human placental lactogen directly inhibits rat cartilage growth processes in vivo and in vitro
Authors: Chiang Mimi H , Kelley Kevin M , Nicoll Charles S
Published: June 2009

We have recently reported that human placental lactogen inhibits the growth of young female rats without changing the serum levels of insulin like growth factor-I. Accordingly, experiments were conducted to determine whether human placental lactogen could directly inhibit cartilage growth processes in vivo and in vitro. Osmotic minipumps with attached polyethylene catheters were used to infuse the hormone for seven days into the left hindlimb of three-month-old female rats via the common iliac artery. The right hindlimb of each animal served as an internal control. Infusion of the placental lactogen at 10 μg/rat/day caused a slight (10%) but significant decrease in the width of the tibial epiphysial cartilage plate and a higher dose (100 μg/rat/day) caused a greater degree of inhibition (25%). However, the higher dose also inhibited the tibial cartilage plate of the contralateral (non-infused) limb. The possibility that human placental lactogen could directly inhibit cartilage anabolic activity in vitro was evaluated by measuring the incorporation of 35SO4 into costal cartilage explants from three to four-month-old female rats. The placental hormone inhibited the incorporation of 35SO4 in a dose-related manner at concentrations ranging from 1.0 to 100 μg/l. As a test of the specificity of this inhibition the effect of the hormone on the incorporation of 35SO4 into cartilage explants from Coho salmon was determined. The placental lactogen did not affect incorporation of the sulfate into the fish cartilage over a range of doses from 1.0 to 1000 μg/l. These results indicate that at least some of the inhibitory effects of human placental lactogen on the growth of rats is direct on peripheral tissues, such as cartilage. This effect may be mediated by the well-established anti-insulin action of the placental hormone.
Insulin-like growth factor binding protein-1 from Hep G2 cells is potently inhibited by the truncated IGF-I analogue des-(1-3) IGF-I
Authors: Lindgren Björn F , Isaksson Monica , Stern Ingrid , Hall Kerstin
Published: June 2009

Des-(1-3) insulin-like growth factor-I (IGF-I) is an IGF analogue lacking aminoacid 1 to 3 which displays reduced binding to insulin-like growth factor binding protein-1 (IGFBP-1). A greater inhibition of immunoreactive IGFBP-1 was obtained with des-(1-3) IGF-I (10 ng/ml) in Hep G2 medium when incubated in Eagle's Modified Essential Medium (EMEM) without phenolred compared to EMEM with phenolred; EMEM without phenolred was chosen for further experiments. Des-(1-3)IGF-I decreases dose dependently the concentration of IGFBP-1, with a maximal effect at 3–10 μg/l when incubated for 24 h; 10 μg/l of des-(1-3)IGF-I caused a small but significant inhibition of IGFBP-1 after 8 h incubation and this inhibition was 41% and 33% of controls after 14 and 19 h incubation. The relative potencies at 16 h of incubation of IGF-I and insulin in suppressing IGFBP-1 in comparison to des-(1-3)IGF-I were 0.41 (0.25–0.78) and 0.08 (0.01–0.26), respectively. A dose-dependent decrease of IGFBP-1 mRNA to 30% of control was observed after 4 h incubation with 0.1–10 μg/l des-(1-3)IGF-I. Changes of glucose concentration (0–20 mmol/l) in the medium did not affect the IGFBP-1 concentration in the medium. In summary: Des-(1-3)IGF-I was tenfold more potent than insulin, and threefold more potent than IGF-I in decreasing IGFBP-1 concentration in medium conditioned by Hep G2 cells.
Adrenaline and noradrenaline responses during insulin-induced hypoglycaemia in man: should the hormone levels be measured in arterialized venous blood?
Authors: Liu Dating , Andréasson Karin , Lins Per-Eric S , Adamson Ulf CK , Macdonald Ian A
Published: June 2009

To compare arterial, arterialized venous and venous measurements of plasma catecholamines during hypoglycaemia, six healthy men were studied by an iv infusion of insulin (1034 pmol·kg−1·h−1), Arterial blood glucose was clamped at the baseline level for the first 30 min and then reduced to 3.2 and to 2.5 mmol/l for 20 min subsequently. At each stage, arterial, arterialized venous and venous blood samples were simultaneously taken for analyses of plasma catecholamines. Plasma glucagon significantly declined during hyperinsulinaemic euglycaemia and then increased during hypoglycaemia. Plasma adrenaline and noradrenaline increased significantly during hypoglycaemia. During euglycaemia and mild hypoglycaemia, arterial adrenaline tended to be higher and arterial noradrenaline lower as compared with the corresponding arterialized and venous values. During marked hypoglycaemia, the arterial catecholamines were significantly higher than that of the two venous samples (p<0.05). There was a significant correlation between the arterial and the arterialized as well as venous catecholamine values (p<0.005). We conclude that, during euglycaemia and mild hypoglycaemia, the arterialized adrenaline values are closer to the arterial levels whereas the arterialized noradrenaline concentrations are similar to those measured in venous blood. However, during marked hypoglycaemia, both the arterialized adrenaline and noradrenaline are 20–30% lower than the arterial values, being close to the venous levels.
Responses of insulin-like growth factor binding protein-1 (IGFBP-1) and the IGFBP-3 complex to administration of insulin-like growth factor-I
Authors: Baxter Robert C , Hizuka Naomi , Takano Kazue , Holman Sara R , Asakawa Kumiko
Published: June 2009

The importance of insulin-like growth factor binding proteins (IGFBPs) in modulating the bioactivity of administered IGFs is poorly understood. This study examines responses of IGFBP-1 and the IGFBP-3 complex to recombinant human IGF-I. Eight fasted subjects received a single dose of 0.1-0.125 mg/kg IGF-I sc. This caused a 10-fold rise in IGFBP-1 over 6 h. falling rapidly after food intake. Peak (6-h) IGFBP-1 values were highly correlated with peak post-prandial (8-h) glucose values (r = 0.941). IGFBP--3 showed little response, decreasing slightly over the 48-h period following IGF-I. Adaptive changes in IGFBPs were studied in fed adults injected daily for 7 days with IGF-I, 0.1 mg/kg sc. Following the first injection. IGFBP-1 had a markedly blunted response compared to that in fasted subjects. However, after the seventh IGF-I injection, a 3.5-fold greater IGFBP-1 response to the same IGF-I dose was seen. Concomitantly with the increased IGFBP-1 responsiveness, mean immunoreactive IGFBP-3 and acidlabile subunit levels decreased significantly (p< 0.005), whereas IGFBP-2 detected by immunoblotting increased. Thus IGF-I administration causes changes in IGFBPs which may be important in regulating IGF-1 bioavailability.
Nocturnal versus diurnal hormonal counterregulation to hypoglycemia in Type 1 (insulin-dependent) diabetic patients
Authors: Bendtson Inger , Rosenfalck Anne Mette , Binder Christian
Published: June 2009

Asymptomatic hypoglycemia in IDDM patients seems to be more frequent during the night than during the day, with reported frequencies as high as 56%. Hormonal counterregulation to diurnal and nocturnal hypoglycemia was studied in 10 insulin-dependent diabetic patients without diabetic complications in order to test whether hormonal responses were lower at night than during daytime. A lower catecholamine response might imply less marked symptoms and therefore one reason why patients are not awakened by hypoglycemia. Blood glucose was stabilized to around 6 mmol/1 by iv insulin infusion and hypoglycemia was induced by increasing the insulin infusion rate—in the night studies at 01.30, in the day studies at 08.00. Blood glucose nadirs were 1.5±0.4 (1.2–1.9) mmol/1 at night and 1.9±0.3 (1.3–2.2) mmol/l during the day; in three patients the nadirs were identical during both the night and day. One patient had no adrenaline response to daytime hypoglycemia. In general, nocturnal hypoglycemia elicited greater catecholamine responses correlated to the duration of hypoglycemia. Glucagon responses showed a great heterogeneity independently of diabetes duration and hypoglycemic level. Growth hormone secretion was reduced during the night study; however, no refractory periods were found after sleep-related growth hormone secretion. In conclusion: counter-regulatory hormonal responses tend to be greater at night than during the day and do not explain why patients are not awakened by nocturnal hypoglycemia.
Immunodetection of TSH receptor antibodies in sera of patients with autoimmune thyroid disease by ELISA (enzyme-linked immunosorbent assay)
Authors: Ikeda Masato , Ohmori Masayuki , Endo Toyoshi , Onaya Toshimasa
Published: June 2009

An ELISA system has been developed for detecting antibodies to TSH receptor peptides. It has been used to study antibodies against peptides corresponding to four different extracellular domains of human TSH receptor in the sera of patients with Graves' disease (N = 10, TBII positive) and Hashimoto's disease (N= 10, TBII negative). Two peptides, N (amino acid residues nos. 29-57) and P3 (nos. 359-371) are specific for TSH receptor, and two, C (nos 172-202) and P1 (nos. 398-417) are homologous with the corresponding portions of the LH/CG receptor. All of the peptides were recognized by sera from patients with Graves' disease but individual sera recognized different numbers and combinations of these peptides. Sera from patients with Hashimoto's disease did not bind to any of these peptides. These results suggest that antibodies to the TSH receptor in patients with Graves' disease recognize various regions of extracellular domain of TSH receptor in addition to TSH receptor-specific regions.
Effect of long-term treatment with bromocriptine on the growth hormone response to galanin in patients with acromegaly
Authors: Giustina Andrea , Doga Mauro , Bussi A Rosa , Licini Massimo , Schettino Maurizio
Published: June 2009

Galanin elicits growth hormone (GH) secretion in normal man but may cause a paradoxical fall of GH in acromegaly. The aim of our study was to investigate the effects of long-term treatment with bromocriptine on the galanin-induced GH decrease in acromegalic subjects. Six acromegalic patients (5F, 1M) chronically treated with bromocriptine underwent in randomized order: (i) iv infusion of 100 ml saline from 0 to 45 min and (ii) iv infusion of synthetic porcine galanin (0.5 mg in 100ml saline) from 0 to 45 min. In acromegalic patients, GH values fell from baseline (10.5±2.7 μg/1) to a mean nadir of 6.9±2.2 μg/1 after galanin infusion (57.8±9.4% vs basal levels). Saline infusion did not cause any change in circulating GH levels. The mean change in GH values with respect to baseline after galanin in these subjects significantly differed from that observed after saline from time 15 to 90 min. Serum prolactin levels were not significantly affected by galanin. Our results confirm that the dose of galanin capable of increasing plasma GH levels in normal subjects can decrease GH values in patients with acromegaly. Moreover, our data show that this paradoxical GH decrease induced by galanin can also be observed in patients chronically treated with bromocriptine. Therefore, the paradoxical decreasing effect of galanin on plasma GH levels in acromegaly seems not to be mediated via dopaminergic pathways.
Altered adrenal steroid production in term infants having respiratory acidosis
Authors: Harlin Cindy A , Tucker James M , Winkler Cary L , Henson Brenda , Parker Charles R
Published: June 2009

Prior studies have provided evidence for reduced fetal adrenal production of dehydroepiandrosterone sulfate and normal or increased production of cortisol in association with pregnancy complications believed to result in fetal stress. In the present study, we sought to determine the status of adrenal steroidogenesis in 36 term infants having respiratory acidosis and to compare acidotic infants to (i) non-acidotic infants matched for pregnancy complications, gestational age, and method and indications for delivery (control infants), and (ii) non-acidotic infants of non-complicated pregnancies who were also matched for gestational age and delivery method (normal infants). Umbilical cord serum levels of dehydroepiandrosterone sulfate were lowest in acidotic infants, intermediate in the condition matched control infants and highest in the non-acidotic infants of normal pregnancies. On the other hand, cortisol levels were highest in acidotic infants, intermediate in control infants and lowest in the normal infants. These data suggest that various pregnancy complications give rise to significant alterations in adrenal steroidogenesis (decreased dehydroepiandrosterone sulfate and increased cortisol). Intrauterine deterioration during labor with resultant respiratory acidosis has an additional effect on fetal adrenal function.
Cortisol increases plasma insulin-like growth factor binding protein-1 in humans
Authors: Conover Cheryl A , Divertie Gavin D , Lee Phillip DK
Published: June 2009

Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the metabolic and mitogenic actions of the IGF peptides. Previous studies have established insulin as the major regulator of plasma IGFBP-1 in humans, acting to suppress hepatic IGFBP-1 synthesis. In this study, we investigated the regulation of plasma IGFBP-1 by cortisol in humans, independent of insulin. Following an overnight fast, six healthy adult volunteers received a euglycemic pancreatic clamp (somatostatin, 0.12 μg·kg−1·min−1; GH, 3 ng·kg−1·min−1; insulin, 0.05 mU·kg−1·min−1) to block endogenous insulin secretion and to control glucose and plasma hormone concentrations at desired levels. Three hours after the initiation of the pancreatic clamp, each subject received an additional 360 min infusion of either cortisol (2 μg·kg−1·min−1) or saline on separate occasions and in random order. Plasma cortisol concentrations increased from 220 to 970 nmol/1 during the cortisol infusion. Insulin concentrations were maintained at approximately 30 pmol/1 throughout saline and cortisol infusions. Plasma IGFBP-1 concentrations increased threefold in response to hypoinsulinemia, reaching plateau values of ∼ 140 μg/l with saline infusion. During cortisol infusion, IGFBP-1 levels increased to ∼300 μg/I. Over the 360 min study period, the integrated response of plasma IGFBP-1 to cortisol infusion was 314% greater than to saline infusion (p <0.01). Our data confirm that, under conditions of hypoinsulinemia, cortisol is a significant modulator of plasma IGFBP-1 in humans.
Graves' disease, endocrine ophthalmopathy and smoking
Authors: Winsa Brita , Mandahl Agneta , Karlsson F Anders
Published: June 2009

We have evaluated the association between smoking, Graves' disease and endocrine ophthalmopathy in a case-control study of 208 patients with newly diagnosed Graves' disease and carried out a retrospective survey of 72 patients treated for Graves' disease and admitted to our ward because of endocrine ophthalmopathy. In the prospective study, patients with Graves' disease smoked significantly more than their healthy controls (41% vs 30%, p<0.01 for current smokers, odds ratio 1.6, 95% confidence interval 1.1-2.3, and p<0.05 for patients with a history of smoking, odds ratio: 1.4, 95% confidence interval 1.0-1.9). Among the patients with endocrine ophthalmopathy at diagnosis, there were slightly more patients with a history of smoking (p <0.05, odds ratio 2.1, 95% confidence interval 1.1-3.9), but not more current smokers when compared with the remaining group. The patients with eye problems tended to have a more active disease with higher levels of thyroxine and TSH-receptor antibodies, but no difference was seen in thyrogastric autoantibodies. No effect of smoking on thyroid hormone and autoantibody levels could be detected. In the retrospective survey we found 64%, 71% and 87% smokers among patients with moderate, severe and malignant eye disease, respectively. In summary, the results show that smoking is associated with an increased risk of contracting Graves' disease and that it enhances the severity of the eye disease in cases that develop endocrine ophthalmopathy during the course of treatment.