bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of TSH receptor binding and thyroid stimulating antibodies following antithyroid drug treatment of Graves' disease
Authors: Wilson R. , Fraser W. D. , McKillop J. H. , Thomson J. A. 
Published: December 2008

Abstract.
Following a course of medical therapy for Graves' disease approximately 50% of patients relapse. Previous studies have tried to identify these patients by measuring antibodies to the TSH receptor using a range of assay methods. Such studies have produced widely discrepant results. The aim of the present study was to compare the accuracy with which TSH receptor binding antibodies and thyroid-stimulating antibodies could identify cases of relapse and remission. Fifty-six newly diagnosed and previously untreated Graves' disease patients were recruited into the study. At presentation 4 were negative for TSH receptor antibody and 5 negative for TS-ab. The remaining 47 were positive for TSH receptor antibody and TS-ab although correlation of the degree of abnormality between methods was poor (r = 0.13 NS). After 12 months carbimazole treatment 28 patients relapsed during the following year and 19 remained in remission. TSH receptor antibody levels obtained at the end of a 12-month course of treatment correctly identified 93% who relapsed and 95% who remained in remission. TS-ab levels could only correctly identify 68% who relapsed and 53% who remained in remission. These results have shown that the accuracy with which patients likely to relapse can be identified depends on the assay method chosen which may account for some of the discrepancies found in previously published studies.
Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement
Authors: Sturgess Ian , Thomas Simon H. , Pennell Dudley J. , Mitchell Derek , Croft Desmond N. 
Published: December 2008

Abstract.
Eleven patients with treated hypothyroidism were investigated to examine the effects of time on their thyroid function tests. Each patient was clinically and biochemically euthyroid on once daily thyroxine replacement therapy, taken in the morning. TSH followed a diurnal rhythm with a peak level at 23.30 h and a trough level at 14.30 h. Four subjects had TSH trough levels within the normal range, but with peak levels outside this range. FT4 and FT3 levels fell from their highest levels some three hours after ingestion to the lowest levels just prior to the next dose. This study shows that there are significant time-related variabilities in TSH and thyroid hormone levels in treated hypothyroid patients. This should be taken into account when interpreting results of their thyroid function tests.
Single-dose response study of the somatostatin analogue octreotide in acromegaly
Authors: van Liessum Peter A. , Pieters Gerlach F. , Smals Anthony G. , Hermus Ad R. , Benraad TheoJ. , Kloppenborg Peter W. 
Published: December 2008

Abstract.
The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 μg daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 μg octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 μg. The 400 μg octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 μg/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 μg than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 μg injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 μg octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 μg octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 μg doses are superior to 25 μg, but do not differ from each other.
Partial loss of responsiveness of human fetal pituitary cells to hGHRH after chronic exposure
Authors: Blumenfeld Zeev , Tapaneinen Paivi , Kaplan Selna L. , Grumbach Melvin M. , Jaffe Robert B. 
Published: December 2008

Abstract.
Synthetic hGHRH was incubated with dispersed pituitary cells from 14 human fetuses at 14–23 weeks of fetal age. After at least three days following plating the cells on an extracellular matrix in serum-containing medium, 3 h incubation with hGHRH in serum-free medium induced a significant increase in GH secretion into the medium at concentrations of hGHRH of 0.01 nmol/1 or higher. After 24 h exposure to 0.5 nmol/1 hGHRH, subsequent incubation with 0.5 nmol/1 hGHRH for 3 h induced significantly lower GH secretion into the medium compared to the GH secretion by cells exposed previously to medium alone. In contrast, when the subsequent exposure to hGHRH was at 10-fold higher concentrations than the concentration present in the initial exposure, GH secretion into the medium did not significantly decrease compared to previously untreated cells. These results suggest that desensitization (down-regulation) of GHRH receptors on somatotropes may be involved in the mechanism by which prior GHRH exposure inhibits GH secretion in response to subsequent GHRH administration. Such desensitization seems to occur in the human fetus but is incomplete. The desensitization may be overcome by increasing the GHRH concentrations with subsequent exposure, suggesting that cellular GH depletion is not responsible for the decreased responsiveness observed.
Immunocytochemical localization of the sex hormone-binding globulin in a human hepatoma cell line
Authors: Luppa P. , Oettrich K. , Schwab I. , Langmandel U. , Neumeier D. 
Published: December 2008

Abstract.
The human hepatoma cell line HEP G2 was investigated in an indirect immunofluorescence study for localization of the sex hormone-binding globulin. Cells were grown directly to confluency on the slides used for the immunocytochemical staining. A fine granular cytoplasmatic fluorescence pattern revealed the presence of sex hormone-binding globulin. Chang-liver cells used as controls, incubated under the same conditions, did not fluoresce. The synthesis of the hormone-binding protein in HEP G2 cells, which could be stimulated by L-thyroxine in the culture medium, was monitored by either indirect immunofluorescence or by immunoradiometric determination of sex hormone-binding globulin in the supernatant. These studies demonstrate that immunofluorescence techniques are able to detect sex hormone-binding globulin in human hepatoma cells.
A case of normotensive primary aldosteronism with hypopituitarism, epilepsy, and medullary sponge kidney
Authors: Kuroda Takeo , Okamura Ken , Yoshinari Mototaka , Ikenoue Hiroshi , Sato Kaori , Yamashita Yoshiaki , Takishita Shuichi , Fujishima Masatoshi 
Published: December 2008

Abstract.
A 55-year-old man with normotensive primary aldosteronism, hypopituitarism, epilepsy, and medullary sponge kidney is reported. Seventeen years before admission, he had been noted to have hypokalemia associated with high potassium clearance, suppressed plasma renin activity, metabolic alkalosis, and normal blood pressure as well as low urinary excretion of 17-hydroxycorticosteroids. He kept normotensive in spite of hyperaldosteronism until nine months after the initiation of replacement therapy with glucocorticoid and thyroxine for hypopituitarism, when he became hypertensive. Hypopituitarism seemed to play a role in keeping a normal blood pressure despite long-standing hyperaldosteronism.
Diagnostic value of bioactive FSH in male infertility
Authors: Jockenhövel Friedrich , Khan Shafiq A. , Nieschlag Eberhard 
Published: December 2008

Abstract.
Bioactive FSH and immunoreactive FSH were determined in 193 infertile men and in 23 men with proven fertility using the Sertoli cell aromatase bioassay for bioactive FSH measurement and a two-site fluoroimmunoassay for immunoreactive FSH measurement. Overall bioactive and immunoreactive FSH levels correlated well (r = 0.74, p < 0.001) but were significantly different from fertile men (bioactive FSH: 6.2 ± 0.3 U/l; immunoreactive FSH: 4.1 ± 0.4 U/l) in patients with Klinefelter's syndrome (24.1 ± 6.1; 26.9 ± 3.0), non-obstructive azoospermia (25.1 ± 4.3; 22.2 ± 4.0), maldescended testes (12.5 ± 4.6; 14.6 ± 1.6), and patients with severe oligozoospermia (11.9 ± 1.2; 11.2 ± 1.0). Infertile men with moderate oligozoospermia (8.9 ± 1.5; 8.0 ± 1.1) and normal sperm counts (9.6 ± 1.1; 7.6 ± 1.0) had insignificantly elevated bioactive FSH and immunoreactive FSH levels. Bioactive to immunoreactive FSH ratios were significantly reduced in all patient groups except for patients with normal sperm counts when compared with fertile men. A considerable number of patients exhibited elevated immunoreactive FSH concomitant with normal bioactive FSH levels. We conclude that 1. determination of immunoreactive FSH suffices for classification of patients; 2. bioactive to immunoreactive FSH ratios are reduced in infertile men; 3. some men might secrete immunoreactive FSH with reduced bioactivity.
Decreased anterior pituitary T3 nuclear receptors in a Walker 256 carcinoma-bearing rat model of nonthyroidal disease
Authors: Hupart Kenneth H. , DeFesi Charles R. , Katz Claire P. , Shapiro Lawrence E. , Surks Martin I. 
Published: December 2008

Abstract.
Rats bearing the Walker 256 carcinoma have decreased pituitary nuclear T3 but normal pituitary TSH content and response to experimental hypothyroidism. To elucidate further the role of T3 receptor occupancy and biological response in the tumor-bearing rat model of nonthyroidal disease, we measured the concentration of T3 nuclear receptors, rTSH and rGH and β-TSH mRNA and GH mRNA in the anterior pituitary of euthyroid rats bearing the Walker 256 carcinoma. The abundance of T3 nuclear receptors was decreased in tumorbearing rats and was associated with a decrease in mRNA content for β-TSH and GH. α-tubulin mRNA was decreased to a comparable degree. The pituitary content of rTSH and rGH was, however, the same as in control animals. Since tumor rats have normal regulation of TSH secretion by thyroid hormone, the present findings suggest that TSH secretion in T rats is maintained by a lower T3 nuclear receptor occupancy than in controls. The decrease in β-TSH mRNA may precede a decrease in TSH synthesis and changes in pituitary TSH stores. Since the decrease in GH mRNA was comparable to the decrease in α-tubulin mRNA, it does not appear to be specifically related to decreased T3 nuclear receptor occupancy. We conclude that, in the tumor-bearing rat model of nonthyroidal disease, decreases in β-TSH mRNA occur despite a decreased T3 receptor occupancy. Both thyroid-dependent and thyroid-independent factors may be involved in regulating β-TSH mRNA.
Effect of GnRH agonists on the thymus in female rats
Authors: Ataya Khalid M. , Sakr Wael , Blacker Charla M. , Mutchnick Milton G. , Latif Zuhair A. 
Published: December 2008

Abstract.
The potential clinical applications of GnRH agonists are growing. We studied the effects of two GnRH agonists on the adult female rat thymus in 4 experiments. GnRH agonists administered sc and continuously significantly increased wet and dry thymic weights (absolute and relative). Thymic enlargement was related to the duration of treatment with GnRH agonists. The maximum increase in thymic weight occurred at approximately 18 days following initiation of treatment with GnRH agonists. Thymic enlargement does not appear to involve enhanced mitotic activity as measured by incorporation of tritiated thymidine into thymic tissue and thymic DNA. Histologic examination and computer-assisted morphometric analysis of thymuses indicated an increase in cortex to medulla ratio most pronounced at 10 and 18 days of GnRH agonist treatment. No consistent increases in splenic weight or bone marrow cell counts were observed. Thymosin alpha-1 but not thymosin beta-4 increased in GnRH agonist-treated rats. Thymic weight correlated negatively with ovarian and uterine weights, relative adrenal weight, serum estradiol, LH, and positively with thymosin alpha-1. Exogenous estrogen administration reversed GnRH agonist-induced thymic weight increase. Whether GnRH agonists have direct thymic effects remains to be determined.
Relationship of nocturnal plasma bioactive and immunoactive ACTH concentrations to cortisol secretion in normal men
Authors: Poland Russell E. , Hanada Koichi , Rubin Robert T. 
Published: December 2008

Abstract.
Plasma concentrations of ACTH and cortisol were measured at 15-min intervals from 22.30 to 07.00 h in 8 normal male volunteers. ACTH was measured both by a modified and sensitized isolated adrenal cell bioassay and by radioimmunoassay. Within-subject correlations between bioactive ACTH and cortisol concentrations ranged between 0.86 and 0.95, with an average correlation of 0.93 (86% shared variance). In contrast, within-subject correlations between immunoassayable ACTH and cortisol ranged between 0.03 and 0.92, with an average correlation of 0.69 (48% shared variance). These results suggest that plasma ACTH concentrations determined by RIA might not accurately reflect the capacity of plasma to regulate the secretion of adrenal glucocorticoids.
Ciamexone in endocrine orbitopathy A randomized double-blind, placebo-controlled study
Authors: Kahaly G. , Lieb W. , Müller-Forell W. , Mainberger M. , Beyer J. , Vollmar J. , Staiger Ch. 
Published: December 2008

Abstract
The influence of ciamexone on the activity and course of endocrine orbitopathy was investigated. Fifty-one patients with active orbitopathy classes II-VI were allocated randomly to two groups: over a period of six months, 26 patients received 300 mg/day ciamexone and 25 patients received placebo tablets. In both groups, prednisolone was administered in addition in the first four weeks. Ophthalmological investigations and clinical tests as well as orbit sonography were carried out before as well as one, three and six months after the beginning of therapy. Before and after treatment, computer tomography of the orbit was performed. Symptoms and signs did not show any significant improvement one and six months after therapy. No differences between the two therapy groups were observed. Detailed examination did not reveal any preferential action of the product on individual parameters. Sonography and computer tomography showed no significant alterations of the thickness of the oculomotor muscles. Thus administration of 300 mg ciamexone once a day as compared with placebo did not show any effect on the course and activity of endocrine orbitopathy.
Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women
Authors: Boesgaard Søren , Hagen Claus , Andersen Anders Nyboe , Fenger Mogens , Eldrup Ebbe 
Published: December 2008

Abstract.
The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women received 5-h infusions of either glucose (N = 6) or dopamine at rates of 0.04 (N = 6), 0.4 (N = 6) and 4.0 μg · kg−1· min−1 (N = 8). After 3 h, 10 mg metoclopramide was given iv. No intergroup differences regarding ACTH and cortisol levels were observed (p>0.05). In a second study six women received dopamine (4.0 μg·kg−1·min−1) or glucose for 18 h. During the infusions cortisol and ACTH levels were similar on the two study days. Administration of metoclopramide (10 mg) after 17 h induced a significant increase in cortisol levels during dopamine infusion (p<0.05), whereas no effect was observed during placebo infusion. ACTH levels were unaffected by metoclopramide. In a third study, 9 normal women and 9 normal men received fenoldopam (0.5 μg·kg −1·min−) or placebo infusions for 3 h. In males, median ACTH and cortisol levels were significantly lower (p<0.05) during fenoldopam compared with placebo infusion. In contrast, fenoldopam did not affect ACTH and cortisol levels in normal women. The results suggest that the effect of dopamine D-1 receptor stimulation on ACTH and cortisol secretion is mainly at the hypothalamic level and that this effect is sex-dependent. In addition, we hypothesize that raised dopaminergic activity for a prolonged period of time may have an inhibitory effect on the hypothalamic-pituitary-adrenal axis. This may be triggered by low estrogen levels.
Failure of pyridostigmine to increase both basal and GHRH-induced GH secretion in the night
Authors: Ghigo E. , Arvat E. , Mazza E. , Mondardini A. , Cappa M. , Müller E. E. , Cammani F. 
Published: December 2008

Abstract.
The aim of this study was to verify that the stimulatory effect of cholinergic agonists on both basal and stimulated GH release observed in the morning persists in the night. The effects of pyridostigmine (120 mg orally), a cholinesterase inhibitor, on both basal and GHRH (1 μg/kg iv) - induced GH secretion were studied in 8 healthy volunteers, aged 22-30 years. In the morning, administration of pyridostigmine induced a significant increase in basal GH levels compared with saline (area under the response curve, mean ± SEM: 277.0 ± 54.0 vs 49.7 ± 8.2 μg·l−1·h−1, p < 0.02) as well as a strong potentiation of the GHRH-induced GH release (2117.6 ± 353.0 vs 427.9 ± 87.0 μg·l−1·h−1, p < 0.02). In the night, GH secretion after pyridostigmine did not differ from saline (194.5 ± 21.9 vs 89.4 ± 28.7 μg·l−1·h−1). Moreover pyridostigmine failed to potentiate the GHRH-induced GH increase (1071.9 ± 170.4 vs 740.2 ± 150.9 μg·l−1·h−1). The pyridostigmine + GHRH-induced GH rise during the night was lower (p < 0.05) than in the morning. All together, these data seem to indicate that cholinergic neurons controlling GH secretion are already maximally stimulated at night. As cholinergic activity negatively modulates SRIH secretion, our findings suggest that a reduced somatostatinergic tone in the hypothalamus is present during the night.
Effect of oral clonidine, insulin-induced hypoglycemia and exercise on plasma GHRH levels in short-stature children
Authors: Gil-Ad I. , Leibowitch N. , Josefsberg Z. , Wasserman M. , Laron Z. 
Published: December 2008

Abstract
Human growth hormone release is affected by a variety of pharmacological and physiological stimuli. We have studied the effect of oral clonidine, insulin hypoglycemia, and exercise on plasma hGH and GHRH levels in 31 healthy short-stature children. Thirteen underwent an oral clonidine test (0.15 mg/m2), 12 an iv. insulin test (0.1 U/kg), and 6 performed exercise (running for 10 min in a defined route). GHRH-1-44 was extracted from plasma on silica columns and determined by RIA. Although all three stimuli induced a marked increase in plasma hGH levels, only clonidine induced a significant increase in plasma GHRH levels. Maximal increment in GHRH during clonidine was 6.82 ± 1.05 pmol/l (mean ± SEM) as compared with 0.51 ± 0.28 and 0.53 ± 0.62 during hypoglycemia and exercise (p<0.0005 and p<0.005), respectively. An additional 24 subjects received TRH 0.2 mg/kg iv: 8 TRH alone, 8 TRH and insulin, and 8 TRH and clonidine. Only insulin potentiated the TRH-induced TSH response with a peak of 22.0 ± 3.2 vs 16.0 ± 0.8 and 15.3 ± 1.5 mU/l (p<0.025) for TRH alone and TRH and clonidine, respectively. It is suggested that clonidine stimulates hGH secretion mainly through an enhancement of GHRH release, whereas stress stimuli such as hypoglycemia and exercise achieve hGH release by a different mechanism, possibly inhibition of somatostatin.
Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta)
Authors: Fingscheidt Ulrich , Weinbauer Gerhard F. , Khan Shafiq A. , Nieschlag Eberhard 
Published: December 2008

Abstract.
Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.
In vitro modulation of porcine Leydig cell steroidogenesis by phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol
Authors: French Joseph T. , Welsh Thomas H. 
Published: December 2008

Abstract
Serum-free primary cultures of neonatal (1-day-old) porcine Leydig cells were used to study the effects of phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol on testosterone and pregnenolone production. Phorbol-12-myristate-13-acetate alone from 0.001-10 μmol/l stimulated testosterone and pregnenolone production, whereas 1,2-dioctanoylglycerol alone had no effect on steroid production, relative to control. Phorbol12-myristate-13-acetate and 1,2-dioctanoylglycerol each inhibited pLH-stimulated testosterone and pregnenolone production. To further clarify the influence of these protein kinase C activators on steroidogenesis, cultured Leydig cells were treated with either phorbol-12-myristate-13-acetate or 1,2-dioctanoylglycerol plus forskolin (an adenylate cyclase activator). Both phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol inhibited forskolin-stimulated testosterone production. Phorbol-12-myristate-13-acetate had no effect on forskolin-stimulated pregnenolone production and only the highest concentration of 1,2-dioctanoylglycerol (100 μmol/l) inhibited forskolin-stimulated production of pregnenolone. These data demonstrate that porcine Leydig cell steroidogenesis can be modulated by interactions of the protein kinase C and protein kinase A second messenger systems.