bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic deglycosylation of porcine thyroid peroxidase: effects on catalytic activity and immunoreactivity
Authors: Moura Egberto G. , Pazos-Moura Carmen C. , Yokoyama Naokata , Dorris Martha L. , Taurog Alvin
Published: June 2009

Thyroid peroxidase is a heme-containing, membrane-bound, glycoprotein enzyme that catalyzes iodination and coupling in the thyroid gland. It is also the antigen for microsomal autoantibodies that are commonly found in the serum of patients with autoimmune thyroid disease. We examined the effect of deglycosylation on the catalytic functions and the immunoreactivity of this enzyme. A highly purified, solubilized, large tryptic fragment of porcine thyroid peroxidase, retaining all of the N-linked glycosylation sites of the native enzyme and displaying full catalytic activity was used. It was deglycosylated by treatment with N-glycanase under nondenaturing conditions. The loss in relative molecular mass after treatment, determined by gel electrophoresis, was about 75% of the estimated molecular weight of the glycan portion of porcine thyroid peroxidase. Lectin blots performed with horseradish peroxidase-conjugated concanavalin A showed a similar loss in relative molecular mass but some residual carbohydrate. The intensity of the carbohydrate stain was consistent with the loss of about 75% of the glycans. Despite this loss, three different assays for catalytic activity of porcine thyroid peroxidase were not significantly decreased. Immunoreactivity measured by immunoblotting and by enzyme-linked immunosorbent assay was also unimpaired. These findings suggest that N-glycanase-sensitive glycans in porcine thyroid peroxidase do not act as antigenic determinants and play a minor role, if any, in catalytic activity and, presumably therefore, in the maintenance of protein conformation.
Anti-triiodothyronine autoantibodies in a euthyroid woman: Confirmation of immunoglobulin G antibodies employing protein A column chromatography
Authors: Sugenoya Akira , Mizuno Emiko , Haniuda Masayuki , Fujimori Minoru , Masuda Hiroyuki , Kasuga Yoshio , Kobayashi Shinya , Iida Futoshi
Published: June 2009

The presence of thyroid hormone autoantibodies was investigated in a 48-year-old non-goitrous woman with high levels of serum total T3 and free T3. Her other thyroid function tests were normal. The presence of thyroid hormone autoantibodies were assessed in serum, acid-charcoal treated serum, IgG fractions and in a purified IgG fraction. The IgG fraction was separated from serum by a protein A-Sepharose CL-4B column chromatography and purified by gel filtration chromatography using Sephacryl S 200. Sera from normal individuals were used as controls. The results showed that the increased serum total and free T3 levels were caused by the presence of anti-T3 IgG autoantibodies. The results also indicate that protein A column chromatography is useful as a screening method for gross qualitative analyses of thyroid hormone autoantibodies.
Growth hormone secretion patterns in relation to LH and estradiol secretion throughout normal female puberty
Authors: Wennink Johanna M.B. , de Waal Henriette A. Delemarre-van , Schoemaker Rik , Blaauw Gert , van den Braken Caro , Schoemaker Joop
Published: June 2009

Pulsatile growth hormone secretion patterns were studied in relation to luteinizing hormone and estradiol release in 33 healthy (pre)pubertal girls. Plasma GH was determined every 10 min, plasma LH and E2 every hour. Night-time GH release was always higher than daytime GH release. During daytime, all GH secretion parameters, except for the basal GH level, increased significantly from the prepubertal stage to stage B4 before (m−) the menarche (p=0.05) and decreased thereafter (p=0.05). During night-time, mean GH level and the fraction of GH in pulses also tended to increase from stage B1 to stage B4m−. The number of high pulses (>8 μg/l) during day and night together tended to increase until stage B4m− and decreased after the menarche (p=0.05). Height velocity did not correlate with the number of high pulses (Kendall τ=0.14, p=0.14). From stage B1 to B4m− high correlations were observed between E2 levels and GH secretion parameters, particularly during the day (τ=0.59-0.71, p≤0.01). The correlations between LH levels and GH secretion were high as well (τ=0.50-0.81, p≤0.01), but equal during day and night. It is concluded that during puberty 1. spontaneous GH release in girls increases 2-3 fold until the menarche and decreases thereafter, primarily as the result of an increasing and decreasing GH pulse amplitude; 2. diurnally increasing estradiol levels correlated with increasing GH secretion.
Diagnostic relevance of suppressed basal concentrations of TSH compared with the negative TRH test in detection and exclusion of hyperthyroidism
Authors: Roden Michael , Nowotny Peter , Vierhapper Heinrich , Waldhäusl Werner
Published: June 2009

To evaluate the sensitivity of basal TSH concentrations as determined by an "ultrasensitive" IRMA-assay (RIA-gnost h-TSH-monoclonal, Behring) versus a "negative" TRH test (defined as an increment of TSH ≥0.2 mU/l 20 min after administration of 400 μg TRH iv) in the diagnosis of hyperthyroidism we examined 193 consecutive patients from our thyroid outpatient clinic: 34 patients displayed hyperthyroidism (total T4: 184.4±26.0 μmol/l, effective thyroxine index: 1.25±0.08), whereas 12 had isolated T3-hyperthyroidism (total T3: 3.47±0.48 nmol/l). Employing the producer's definition of subnormal ("suppressed") bTSH concentrations (≤0.1 mU/l), only 19 (41.3%) hyperthyroid patients would have been detected; on the other hand, one euthyroid patient would have been recognized false positively as hyperthyroid. Using the TRH test as criterion led to the correct diagnosis in 42 (sensitivity: 91.3%) hyperthyroid patients, whereas two had low bTSH concentrations (≤0.5 mU/l), but a normal TSH response to TRH (>2.0 mU/l). Raising the threshold concentration to 0.2 and, subsequently, to 0.4 mU TSH/l increased the number of correct results to 38 (sensitivity: 82.6%) and 43 (93.5%), respectively. This was associated with a concomitant decrease in specificity in the diagnosis of hyperthyroidism from 93.7 (0.1 mU/l) to 27.9% (0.4 mU/l). In conclusion, despite ultrasensitive methods for estimation of low TSH concentrations, the TRH test remains an irreplaceable tool for the correct diagnosis of hyperthyroidism.
Hyperthyroidism and thyroid carcinoma
Authors: Ahuja S. , Ernst H.
Published: June 2009

Twenty-two of 251 patients with differentiated thyroid carcinoma suffered from or had a history of hyperthyroidism. They were hyperthyroid with a diffuse goitre (N=4), a diffuse goitre with a cold nodule (N= 10), a multinodular goitre (N=6), and an autonomous adenoma (N=2). Among the 22 patients, more than one fourth had an occult thyroid carcinoma with a diameter of 1 cm or less, those with the papillary tumour types, less frequently had lymph node metastases than the total group of patients with papillary carcinomas (13.3 vs 35.6%). The clinical courses of the 22 patients resembled those of the other thyroid carcinoma patients whose age and initial findings were comparable. In 643 patients who underwent surgery for hyperthyroidism the incidence of thyroid carcinoma was 2.3%. The increase in coincidence of hyperthyroidism and thyroid carcinoma repeatedly reported in recent years is probably ascribable primarily to extensive and improved diagnostics and not to a direct connection between hyperthyroidism and development of thyroid carcinoma. On the other hand, our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.
Blood lymphocyte population following 131I treatment for hyperthyroidism
Authors: Blomgren Henric , Wasserman Jerzy , Petrini Björn , von Stedingk Lars-Viktor
Published: June 2009

A number of immunological parameters have been monitored for up to 6 weeks following 131I treatment for hyperthyroidism in Graves' disease. The aim was to examine whether this isotope treatment normalizes or further accentuates some immunological abnormalities which may be a manifestation of autoimmune reactions in these patients. It was confirmed that both the cellular composition and immunological reactivities of the patients' blood lymphocytes were abnormal before treatment. After 131I administration a slight lymphopenia occurred and the ratio between CD4 and CD8 positive T lymphocytes (helper-inducer/suppressor-cytotoxic), which was increased before treatment, increased further. Moreover, PWM-triggered IgM secretion in vitro was reduced by 50%. No other immunological parameters studied, such as secretion of other Ig classes, mitogenic responses of lymphocytes, and distribution of other lymphocyte subsets, changed to any detectable extent. It remains speculative whether the 131I-induced changes of the immune system may further accelerate the underlying autoimmune disease processes.
Persistence of altered metabolic responses to beta-endorphin after normalization of body weight in human obesity
Authors: Giugliano Dario , Cozzolino Domenico , Torella Roberto , Lefebvre Pierre J , Franchimont Paul , D'Onofrio Felice
Published: June 2009

The responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human β-endorphin (0.5 mg/h) were studied in 10 formerly obese subjects who had lost 35 kg by dieting (body mass index <25) and compared with those of 10 normal-weight control (body mass index <25) and 10 obese (body mass index >30) subjects. The fasting plasma concentrations of β-endorphin were significantly higher in both the obese and the post-obese group than in the control group. In both obese and post-obese subjects, the infusion of β-endorphin caused significant increases in peripheral plasma glucose, insulin, C-peptide and glucagon concentrations. In the control group, matched for age, sex and weight with the formerly obese group, there was no appreciable change in plasma insulin and C-peptide concentrations during the infusion of β-endorphin, but the rise in plasma glucose was more sustained. Thus, 1. the increased plasma β-endorphin concentrations found in human obesity are not corrected by normalization of body weight; and 2. formerly obese, normal-weight subjects behave as obese subjects in their metabolic and hormonal responses to β-endorphin infusion. The alteration of the opioid system in human obesity may play some role in the predisposition to weight gain.
Free thyroxine and 3,3',5'-triiodothyronine levels in cerebrospinal fluid in patients with endogenous depression
Authors: Kirkegaard Carsten , Faber Jens
Published: June 2009

Total and free concentrations of T4 and rT3 in serum and cerebrospinal fluid were estimated by ultrafiltration in 12 patients with unipolar endogenous depression before and after electroconvulsive treatment. Recovery from depression resulted in a decrease in CSF concentrations of free T4 (median) (26.2 to 21.4 pmol/l, p<0.02) and free rT3 (14.1 to 12.3 pmol/l, p<0.05). Concentrations of free T4 in the cerebrospinal fluid were lower than those in serum (p<0.02), the ratio being 0.6. In contrast, levels of free rT3 in the cerebrospinal fluid were considerably higher than those found in serum (p<0.01), the ratio being 25. These ratios did not change following recovery from depression. In 9 patients with nonthyroidal somatic illness, concentrations of free T4 and rT3 in the cerebrospinal fluid were similar to those found in patients with endogenous depression, whereas 4 hypothyroid patients and one hyperthyroid patient had considerably lower and higher, respectively, concentrations of both free T4 and rT3. In conclusion, levels of free T4 and free rT3 in the cerebrospinal fluid are increased during depression compared with levels after recovery, probably reflecting an increased supply of T4 from serum and an increased production of rT3 from T4 in the brain. The data also suggest that the transport of iodothyronines between serum and the cerebrospinal fluid is restricted.
Mechanism of thyroid stimulation by human chorionic gonadotropin in sera of normal pregnant women
Authors: Yoshimura Masayoshi , Nishikawa Mitsushige , Yoshikawa Norio , Horimoto Masateru , Toyoda Nagaoki , Sawaragi Isamu , Inada Mitsuo
Published: June 2009

To elucidate the mechanism of thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the effect of blockade of the TSH receptor on the serum-induced cAMP accumulation and the effect of hCG on the TSH binding to FRTL-5 cells. In the presence of crude immunoglobulin fractions in sera from patients with primary hypothyroidism, cAMP accumulation induced by both crude and purified hCG, and normal pregnant women serum were significantly inhibited compared with that in the presence of normal IgGs. The mode of inhibition of these IgGs on the cAMP accumulation was similar for TSH and hCG when analysed by Lineweaver-Burk plots. Moreover, binding of [125I]TSH to the TSH receptor in porcine thyroid cell membrane was apparently inhibited by adding 4×106 IU/l of purified hCG. Binding studies of TSH in FRTL-5 cells also indicated the dose-dependent displacements of [125I]TSH by hCG. Although half-maximal inhibitory- concentration of hCG was about 20 times as high as that of TSH on a molar basis, displacement of [125I]TSH was observed at a concentration of hCG of 105IU/l or more, which could be a physiological concentration of hCG in sera of normal pregnant women. These results suggest that thyrotropic activity of hCG in sera of normal pregnant women is, at least in a part, mediated by TSH receptors.
Autonomous progesterone secretion from the bovine corpus luteum in vitro
Authors: Rossmanith Winfried G. , Schick Markus , Benz Reiner , Lauritzen Christian
Published: June 2009

While the regulation of progesterone secretion from the corpus luteum by LH has been convincingly demonstrated, the secretory patterns in the absence of any pituitary LH inputs are yet unclear. Consequently, we investigated the progesterone secretion by an in vitro perifusion system to characterize spontaneous progesterone release from the isolated bovine corpus luteum. Slices (120 mg) of midluteal corpora lutea were placed in perifusion chambers and continuously perifused by Medium-199 for 160-320 min. Progesterone was determined by radioimmunoassay in the effluent fractions collected at 2-min intervals. The spontaneous progesterone release from all bovine corpora lutea was pulsatile. Pulses were observed at mean (±sem) intervals of 17.7±1.5 min with amplitudes of 6.7±0.5 ng and release rates of 29.5±2.4 ng · ml−1 · (2 min)−1 (N=5). Addition of 6.7 nmol/l hCG to the perifusion medium appeared to increase the pulse amplitudes and release rates (195±25% over unstimulated conditions), but did not change the pulse frequencies (N=3). Perifusions with calcium-free medium containing 50 μmol/l verapamil and 20 mmol/l EGTA tended to suppress the pulse frequencies and amplitudes of this spontaneous progesterone release, whereas addition of hCG reversed this decrease again (N=3). When prostaglandin activity was inhibited by 100 μmol/l indomethacin added to the perifusion medium, both pulse frequencies and amplitudes of this progesterone release were enhanced (N=4). During perifusions with 100 μmol/l of the anti-progesterone ZK 96.734, both the pulse frequencies and amplitudes increased (N=4). These studies demonstrate an episodic progesterone release from the bovine corpus luteum perifused in vitro. The spontaneous progesterone secretion is independent of, but facilitated by gonadotropin secretion. This pulsatile progesterone secretion from the midluteal corpus luteum and its regulation by intraovarian factors may reflect an autonomous pulse generating mechanism.
Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse
Authors: Kanda Shigeru , Saha Pabitra K. , Nomata Koichiro , Taide Masakatsu , Nishimura Naoki , Igawa Tsukasa , Yamada Jun , Kanetake Hiroshi , Saito Yutaka
Published: June 2009

A sensitive enzyme-linked immunosorbent assay for mouse epidermal growth factor was established for measurement of the content of epidermal growth factor in the remaining kidney after uninephrectomy. In 5-week-old male mice, the renal epidermal growth factor content before uninephrectomy was 355±97 ng/g wet tissue with a 2.1-fold increase on the first day after uninephrectomy, whereafter it gradually decreased. In 15-week-old mature male mice, the renal epidermal growth factor content increased 1.7-fold on the first day after uninephrectomy. Immunohistochemical analysis showed that epidermal growth factor was present in the distal tubular cells and that the staining intensity was increased on the first day after uninephrectomy. During the course of compensatory renal growth, no significant alteration of epidermal growth factor content was observed in plasma or in the submaxillary gland. Our data suggest that the increase in renal epidermal growth factor content after uninephrectomy is due to an increased production of epidermal growth factor in the kidney itself. The significance of this phenomenon is discussed.
Objective assessment of concordance of secretory events in two endocrine time series
Authors: Guardabasso Vincenzo , Genazzani Alessandro D. , Veldhuis Johannes D. , Rodbard David
Published: June 2009

A new objective method is presented for investigating the presence of a temporal relationship between episodic release of two hormones. The two time series of hormone concentrations are first analysed by an objective method for peak detection. Both data series are then transformed into "quantized" or discretized series by recording the occurrence of a hormone pulse as an "event", characterized by the onset, the maximum, or another unique feature. The two quantized series are then matched, and the number of concordant events and discordant events are counted. Each point in series A is compared with a "time-window" of a selected number of points in series B, to accommodate small degree of mismatch between events in the two series. An index of concordance is computed, compensating for any spurious random coincidence: the "Specific Concordance", to evaluate the frequency of concordant events in excess of those expected on the basis of chance alone. This calculation is systematically repeated, interposing a range of time-lags between the two series. A graph of Specific Concordance versus time-lag indicates the time-lag corresponding to a maximal concordance. Simulations of random series of events are performed, and their degree of concordance is evaluated in a similar fashion, thus generating frequency distributions of Specific Concordance values under the null hypothesis of no temporal relationship. This permits the selection of criteria for statistical significance at any desired p-level, for one or many lag times, and for one or multiple subjects. Various degrees of concordance can also be simulated to evaluate the performance (sensitivity, statistical power) of this approach. These methods have been implemented as a collection of short microcomputer programmes, and applied to the study of the temporal relationship between β-endorphin and cortisol in normal subjects sampled every 10 min for 24 h. This analysis demonstrated concordance between events in the two series, with synchronous occurrence of β-endorphin and cortisol release events significantly more frequently than expected on the basis of random association (p<0.01).
Urine steroid excretion rates in childhood reflect growth and activity of the adrenal cortex
Authors: Honour J. W. , Kelnar C. J. H. , Brook C. G. D.
Published: June 2009

Normal ranges for daily urine steroid excretion rates in childhood are reported for the first time by gas chromatographic analysis using capillary columns and flame ionisation detector. Longitudinal data came from a study over 3 years of 127 normal boys (aged 7.5-15.6 years) studied on 5 occasions and 14 pubertal girls studied over 2 years. Cross-sectional data were collected from 115 hospitalized patients (58 males, 57 females) aged 2.9 to 14 years with normal adrenal function. The excretion rate of cortisol metabolites was constant for body size, whereas androgen metabolite excretion rates rose sharply in childhood to approach adult levels at the end of puberty. The new data will enable better interpretation of pediatric patient data.
Regulatory peptides in the thyroid gland — a review on their localization and function
Authors: Ahrén Bo
Published: June 2009

It has been demonstrated that nerve fibres storing immunoreactivity of vasoactive intestinal polypeptide, peptide histidine iso-leucine, neuropeptide Y, substance P, calcitonin gene-related peptide, galanin, and cholecystokinin exists in the thyroid, though the content of these neuropeptides is lower in the thyroid than in other organs, like in the gut. Furthermore, the parafollicular C-cells have been shown to harbour several different peptides: calcitonin, somatostatin, calcitonin gene-related peptide, gastrin-releasing peptide, katacalcin and helodermin. In addition, other regulatory peptides like atrial natriuretic hormone, growth factors, and cytokines are also produced in the thyroid. This review summarizes today's knowledge on the effects of these peptides on thyroid hormone secretion and their possible role in thyroid physiology. So far, functional studies have failed to establish any convincing effect of substance P, calcitonin gene-related peptide, galanin and cholecystokinin on basal or TSH-stimulated thyroid hormone secretion. In contrast, vasoactive intestinal peptide has convincingly been demonstrated to stimulate thyroid hormone secretion, and neuropeptide Y to potentiate the inhibitory action of noradrenaline on TSH-induced thyroid hormone secretion. This suggests that these two neuropeptides are involved in the intrathyroidal neural regulation of thyroid function. Moreover, the C-cell peptides somatostatin, calcitonin, calcitonin gene-related peptide, and katacalcin seem to be involved as inhibitors of thyroid hormone secretion, whereas both gastrin-releasing peptide and helodermin stimulate thyroid hormone secretion. Atrial natriuretic hormone and growth factors, and cytokines seem to inhibit thyroid hormone secretion. Hence, studies undertaken so far suggest a local intrathyroidal peptidergic regulatory concept, the exact role of which remains to be established.
Serum melatonin during human pregnancy
Authors: Kivelä Aarre
Published: June 2009

Serum melatonin concentrations from 55 pregnant healthy women (13 during the first, 18 during the second and 24 during the third trimester) and 11 non-pregnant control women were measured radioimmunologically at 11.00 h (Study A). In addition, serum melatonin concentrations from 12 women in early and 11 women in late pregnancy were measured every four hours throughout the day (Study B). Serum melatonin levels during the third trimester of pregnancy (76.5±38.3 pmol/l were significantly (p<0.01) higher than those during the first (29.7±9.9 pmol/l and the second trimester (39.1 ± 11.2 pmol/l and those of non-pregnant control women (41.7± 15.5 pmol/l and there was a positive correlation between the week of gestation and serum melatonin at 11.00 h (Study A). A clear diurnal rhythm in serum melatonin concentrations was found both in early and in late pregnancy (Study B). The amplitude and duration of the nocturnal rise of melatonin were higher during late pregnancy, but there was no clear phase shift. Increased serum concentration of melatonin in late pregnancy may be due to increased synthesis and secretion or retarded metabolism of melatonin during late pregnancy.
Thyroid gland volume and echo structure in 13-year-old children in northern Finland
Authors: Takalo Raija M. , Mäkäräinen Hanna P. , Jaakkola R. Kaarina
Published: June 2009

The purpose of this work was to determine by ultrasound the volume and echo structure of the thyroid gland in 13-year-old schoolchildren in northern Finland. 76 healthy schoolchildren underwent cervical ultrasound examinations during the period of Jan-Feb 1990, performed with a real-time scanner using a 7.5 MHz linear transducer and direct contact method. The volume of each lobe was calculated according to the formula for a volume of rotation ellipsoid by multiplication of maximal thickness, width and height of the lobe by the correction factor 0.479. Any focal lesion that could be distinguished in the homogenous thyroid parenchyma was assessed for echogenicity as compared with the normal thyroid gland and was measured with electronic calipers. The mean thyroid volume was 6.5±1.6 ml (mean ±sd), being 6.3±1.8 ml in the boys and 6.7± 1.4 ml in the girls. The sex difference was not significant. The right lobe was significantly larger than the left one (mean 3.7 and 2.8 ml, respectively). Thyroid volume was correlated with body weight and body surface area in both sexes. Abnormal lesions in terms of echo structure were noted in one subject (1.3%). Comparing the results with the findings reported from other countries, it can be concluded that the thyroid volume in these 13-year-old Finnish schoolchildren was about 30% less than that reported for the same age group in the FRG (with insufficient iodine intake) and about 35% more than in 13-year-old schoolchildren in Sweden (with sufficient iodine intake).
Glucocorticoids and adrenal androgens in children with end stage renal disease
Authors: Ferraris Jorge R. , Ramírez José A. , Goldberg Victoria , Rivarola Marco A.
Published: June 2009

We studied the effects of chronic renal failure on the pituitary-cortisol axis and adrenal androgen function in 26 patients (16 male and 10 female), aged 6.5 to 22.5 years (mean 14.5). Ten patients were prepubertal, 8 pubertal, and 8 post-pubertal. All of them were on chronic hemodialysis. Pubic hair development was delayed in 56% of the patients. Serum cortisol was increased in 15 out of the 26 patients. Serum Δ4-androstenedione was high in 11 out of 15 patients in Tanner's stage I or II and in 1 out of 11 patients in Tanner's stage III, IV or V (p<0.01). Serum cortisol was elevated in 10 out of 12 patients with high serum Δ4-androstenedione and in only 5 out of 14 with normal Δ4-androstenedione (p<0.02). Serum dehydroepiandrosterone sulphate was normal in 22 patients and elevated in 4 males. There was a significant inverse correlation between bone age and serum cortisol (r:-0.59; p<0.005) and a significant positive correlation between bone age and serum dehydroepiandrosterone sulphate (r: 0.45 p<0.01). Serum ACTH was normal. A reduction by 50% in cortisol and 78% in dehydroepiandrosterone sulphate was found after dexamethasone suppression, but Δ4-androstenedione did not suppress after dexamethasone. After ACTH stimulation test cortisol increased by 50% and Δ4-androstenedione by 80%. Conclusions: The increased levels of cortisol and Δ4-androstenedione with partial resistance to dexamethasone suggest that these patients have a hypothalamic-pituitary dysfunction similar to that found in Cushing's disease or in chronic stress. The difference in the responses of Δ4-androstenedione and dehydroepiandrosterone sulphate observed is consistent with the existence of different mechanisms of control for these two steroids.
Effects of routine heparin therapy on plasma aldosterone concentration
Authors: Kageyama Yo , Suzuki Hiromichi , Saruta Takao
Published: June 2009

Changes in plasma aldosterone, plasma renin activity, plasma cortisol, serum sodium and potassium concentrations were studied in 9 patients with thromboembolic diseases treated with heparin. Heparin was administered at doses of 700-1000 units/h for 7-10 days. Plasma aldosterone decreased from 239±33 to 114±25 pmol/l during heparin therapy and returned to basal levels after discontinuation of the therapy. In addition, responses to a low sodium intake (3 g/day) and ACTH were examined in 5 patients during and 2 weeks after heparin therapy. The increase in plasma aldosterone caused by low sodium intake was significantly attenuated during heparin therapy (124±5% increase from baseline) as compared with that 2 weeks after heparin therapy (148±7%, p<0.05). On the other hand, ACTH stimulated plasma aldosterone similarly during and at 2 weeks after heparin therapy (increase from baseline: 190±20% vs 193±9%). These results suggest that heparin decreased plasma aldosterone owing to attenuation of the angiotensin Il-induced aldosterone production.
Muscle bioenergetic impairment in hyperthyroid man: A study by 31P NMR spectroscopy
Authors: Kaminsky P. , Robin-Lherbier B. , Walker P. , Brunotte F. , Escanye J. M. , Klein M. , Forrett M. C. , Robert J. , Duc M.
Published: June 2009

Phosphorus nuclear magnetic resonance spectroscopy was used to investigate muscle bioenergetics in 9 hyperthyroid patients who were compared with 9 normal subjects. Using the thenar muscle group as reference, the inorganic phosphate, phosphocreatine and intracellular pH were calculated at rest, during aerobic exercise (0.13 w) and post-exercise recovery. No difference was found at rest. After 5 min of exercise, the hyperthyroid patients exhibited a more important phosphocreatine depletion (41.2±8.2 vs 31.1%±6.5, p<0.02) and a larger pH fall (6.65±0.04 vs 7.01±0.10, p<0.001) than the control subjects. The phosphocreatine recovery rate was not significantly different in hyperthyroid patients and control subjects. These results suggest that exercise requires more ATP in hyperthyroid patients than in normal subjects and that there is excessive dependence on glycolytic metabolism for ATP synthesis in hyperthyroidism. Phosphocreatine resynthesis, reflecting the oxydative metabolism, is not increased. These metabolic disturbances could also supply a partial explanation to the frequent exercise intolerance in hyperthyroid patients.
Renaturalizing the sexually dimorphic profiles of circulating growth hormone in hypophysectomized rats
Authors: Pampori Nisar A. , Agrawal Arun K. , Shapiro Bernard H.
Published: June 2009

Hypophysectomy resulted in a total elimination of measurable circulating growth hormone with an associated loss of body weight gain. The typical sexually dimorphic plasma growth hormone patterns: pulsatile profiles in male rats and tonic-like secretion in female rats, were lost. The male- and female-dependent profiles of plasma growth hormone, monitored from serial blood collections, were restored by administering the hormone through a single electrically controlled external pump attached to an indwelling catheter, and by implanting osmotic pumps intraperitoneally, respectively. Restoring the natural patterns of plasma growth hormone in animals devoid of pituitaries, re-initiated body growth. However, the body weight gains in both sexes of hypophysectomized rats were much greater when rat growth hormone was introduced to the animals in a masculine (pulsatile) pattern that appeared to be independent of pulse frequency, rather than in a continuous feminine profile. Subcutaneous injections, the most commonly reported method of administration, produced low-amplitude, long-lasting plasma peaks that were not as effective as pulse infusion in restoring growth. The procedure allows manipulation of the hormone profile (i.e. number of pulses/day, pulse amplitude, and through duration in the pulsatile pattern, and plasma concentration in the tonic pattern) in order to identify, and thus study the presumed salient components of the pattern regulating growth hormone responses.
Interleukin 6 inhibits human thyroid peroxidase gene expression
Authors: Tominaga Tan , Yamashita Shunichi , Nagayama Yuji , Morita Shigeki , Yokoyama Naokata , Izumi Motomori , Nagataki Shigenobu
Published: June 2009

It has been reported that cytokines, especially interleukin 1 and interferon-γ, inhibit the thyroid hormone secretion and the gene expression of human thyroid peroxidase and thyroglobulin. Interleukin 6 has recently been found to be an important cytokine for the regulation of immunoendocrine interaction and intrathyroidal production of interleukin 6 has been reported. Therefore, we investigated the regulation of thyroid hormone secretion and thyroid peroxidase messenger RNA by interleukin 6 in human thyrocytes to clarify further the functional role of interleukin 6 in thyroid glands. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH with or without interleukin 6. TSH (5 U/l stimulated the expression of thyroid peroxidase mRNA transcripts (4.0, 3.2, 2.1, and 1.7 kb, respectively), although unstimulated thyrocytes contained the low level of 3.2 kb thyroid peroxidase mRNA transcript. Interleukin 6 (104-105 U/l) inhibited TSH-induced thyroid peroxidase mRNA in a dose-dependent manner, although the basal level of thyroid peroxidase mRNA expression was not suppressed by interleukin 6. Interleukin 6 also inhibited 8-bromo-cyclic adenosine monophosphate-induced thyroid peroxidase mRNA levels. In contrast, the γ-action mRNA hybridization signal was not altered in control or treated cells. Subsequently, interleukin 6 inhibited TSH-induced T3 secretion in a dose-dependent manner after 72 h treatment. However, interleukin 6 did not affect DNA synthesis. Pretreatment with specific antibody against interleukin 6 selectively restored the inhibitory effect of interleukin 6 on thyroid peroxidase gene expression. Our results suggest that interleukin 6 plays an inhibitory role in the thyroid gland, in addition to interleukin 1 and interferon γ.
Use of the receiver operating characteristic curve to evaluate sensitivity, specificity, and accuracy of methods for detection of peaks in hormone time series
Authors: Genazzani A. D. , Rodbard D.
Published: June 2009

We utilize the "Receiver Operating Characteristic" to describe the relationship between sensitivity and specificity as the threshold for peak detection is varied systematically, to provide objective comparison of the performance of methods for detection of episodic hormonal secretion. A computer program was used to generate synthetic data with peaks with variable durations, with constant or variable height, shape and/or interpulse interval. This approach was used to compare the CLUSTER and DETECT programs. For both programs, the observed false positive rates estimated using signal-free data were in good agreement with the nominal rates, but in the presence of signal the observed false positive rates were systematically lower. Sensitivity increases with increasing signal/noise ratio, as expected. Program DETECT, using its standard options, provided excellent sensitivity (90-100%) with very low false positive rate under all conditions tested. Its performance could be further improved by the use of a more stringent definition of a peak requiring the presence of "UP" followed by a "DOWN". The CLUSTER program was found to have very poor sensitivity when using the "local variance" option. Use of the true fixed standard deviation or percent coefficient of variation resulted in a modest improvement. Optimal performance of program CLUSTER was obtained by the use of the best of 3 variance models, testing 12 different cluster sizes (from 1×1) to 4×4 and selecting the best among these: under these conditions it can achieve high sensitivity (90-100%) for very low observed false positive rate, such that its performance was comparable to that of DETECT. The methods developed and illustrated here should permit the definitive characterization and validation of the performance of any one method, the objective comparison of the relative performance of two or more methods for analysis of pulsatile hormone levels for episodic hormone secretion, and lead to the improvement of algorithms for peak detection.
Chronic treatment with bovine growth hormone upregulates high-affinity hepatic somatotropic receptors in sheep
Authors: Sauerwein Helga , Breier Bernhard H. , Bass John J. , Gluckman Peter D.
Published: June 2009

We evaluated the effect of chronic bovine growth hormone treatment on the hepatic somatotropic receptor. Growing lambs were treated with bGH at 0, 0.05, 0.15, 0.25 or 0.55 mg · kg−1 · day−1 daily (N=5/group) for 56 days. The binding of ovine GH to hepatic membranes washed with 4 mol/l MgCl2 and prepared in the presence of aprotinin was examined. The specific binding of oGH was increased (p<0.01) from 7.1±1.2% in saline-treated controls to 17.4±1.5% in the 0.55 mg · kg−1 · day−1 group. Scatchard analysis showed curvilinear plots that best fitted a two-site model in 22/25 livers. The two sites had estimated dissociation constants (Kd) of 3 to 13 nmol/l for the low-affinity site and a Kd ranging from 0.17 to 0.31 nmol/l for the high-affinity site. Treatment with bGH had no consistent effect on the affinity of either binding site. However, bGH therapy was associated with a dose-dependent increase (p<0.01) in the number of high-affinity somatotropic receptors. There was no effect of bGH therapy on the concentration of low-affinity binding sites. The concentration of high-affinity receptors correlated with weight gain (r=0.54, p<0.01), fat content (r=−0.54, p<0.01), protein content (r=0.40, p<0.05), and plasma IGF-I (r=0.57, p<0.005). The concentrations of low-affinity binding sites showed no such correlations. These observations demonstrate that an important effect of chronic GH therapy in animals with an intact somatotropic axis is to increase significantly the concentration of high-affinity somatotropic receptors. It is suggested that enhancement of the number of high-affinity somatotropic receptors is central to the determination of the efficacy of GH therapy.
Age-related alterations in prolactin binding sites in the female rat
Authors: Schneiter Philippe , Reymond Marianne J. , Lemarchand-Béraud Thérèse
Published: June 2009

Aging is associated with various neuroendocrine alterations, including in the rat a hypersecretion of PRL with maintained ovulations (repetitive pseudopregnancy) and a reduced activity of the hypothalamic dopaminergic neurons with loss of the neuron responsiveness to PRL, suggestive of age-related alterations in PRL receptors. In this study we have investigated PRL binding sites in the hypothalamus as well as in the mammary glands, the ovaries and the liver of young and old nulliparous female rats. The old rats (26-28 months) displayed spontaneous repetitive pseudopregnancies and they were compared with young (4-6 months) pseudopregnant rats; the binding studies were performed by saturation analysis using 125I-oPRL as ligand and particulate membrane preparations. In the hypothalamus, a negligible binding of PRL was observed in all fragments studied, mediobasal hypothalamus, median eminence, in both young and old rats and no characterization of the binding sites could be achieved. In the mammary glands, the number of PRL binding sites was appreciable in spite of the nulliparity of the rats, but it was smaller in the old than in the young rats (9.0±1.4 vs 14.9±1.2 fmol/mg protein; mean ± sem; p<0.02). In the ovaries, the density of PRL binding sites was similar in the old and young rats (112.6±9.7 vs 115.0±8.9 fmol/mg protein), illustrative of a maintained luteotropic effect of PRL with age in the rat. In contrast, in the liver a greater number of binding sites was found in the old than in the young rats (261.9±36.6 vs 63.6±5.8 fmol/mg protein; p<0.001), supportive of the ability of PRL to induce its own receptors in that tissue. The affinity constant of PRL binding was not altered with age in the tissues studied. These results are illustrative of tissue-specific modifications in the number of PRL binding sites with age and they are suggestive of a sustained biological activity of PRL in the old rats.
Uterine binding sites for LH/hCG can be modulated by hormonal status in rabbits and rats
Authors: Sawitzke Arleen L. , Odell William D.
Published: June 2009

High-affinity LH/hCG binding sites have been identified in both porcine and rabbit uteri. We have now identified these binding sites in rat uteri. We have assessed the binding site specificity and modulation and have searched for binding sites for a related glycoprotein. Radioreceptor assays were performed with membrane homogenates of uterine tissue, and were analysed for binding site specificity, affinity, and capacity. The rabbit and rat LH/hCG binding sites did not bind human TSH or human FSH. Rabbit uterine tissue contained no binding sites for FSH, as determined with 125I-labelled FSH and unlabelled FSH. Pretreatment of rabbits with hCG decreased their uterine binding site capacity from 1.30±0.29 to 0.46±0.01 fmol/mg protein. Pretreatment of castrated rabbits with estrogen or estrogen combined with progesterone did not alter the binding site affinity or capacity. In rats, the uterine binding site number was shown to vary inversely with the serum LH concentration and directly with the ovarian LH/hCG bindig site number during the estrus cycle. Hypophysectomy resulted in a significant increase in uterine binding site capacity in rats. Estrogen treatment prevented this hypophysectomy-induced increase. The function of these LH/hCG binding sites remains uncertain; however, the lack of binding sites for a related glycoprotein and the modulation of these binding sites by hormonal factors strengthen the concept that uterine tissue might respond in a specific manner to direct LH/hCG stimulation.
Partial primary sequence of a human endometrial epithelial progesterone dependent protein secreted in vitro
Authors: Dichek Helen L. , MacLaughlin David T. , Bringhurst F. Richard , Keutmann Henry T. , Richardson George S.
Published: June 2009

We have recently identified a uterine progesterone-dependent 25 kD protein (protein #27) secreted by endometrial epithelial cells but not stroma. Protein #27 was originally isolated from human luteal phase uterine fluids and partially purified by two-dimensional gel-electrophoresis and electroelution. It could not be detected in serum. We here report the further purification and amino terminal sequence of this protein, obtained from in vitro luteal phase endometrial tissue incubation media. Protein #27 was purified by a one-step method using reverse-phase high performance liquid chromatography. Amino acid compositional analysis confirms a high content of nonpolar and hydrophobic residues (40 mol%) and reveals a preponderance of acidic amino acids, consistent with its isoelectric point (5.9-6.3 pH). The amino terminal sequence obtained from a single individual reveals 85% homology with that of pregnancy-associated α2-globulin from pooled cytosolic fractions from pregnancy endometria. We propose that protein #27, secreted by the endometrial epithelium, is an excellent candidate for a marker to be used to study pathological processes of the endometrium such as endometriosis and invasive carcinoma.
Calcitonin gene-related peptide modulates adrenal hormones in conscious dogs
Authors: Murakami Marohito , Suzuki Hiromichi , Nakamoto Hidetomo , Kageyama Yoh , Naitoh Mareo , Sakamaki Youichiro , Saruta Takao
Published: June 2009

The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p<0.05), ACTH (by 85%, p<0.05), AVP (by 89%, p<0.05), and ANH (by 36%, p<0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p<0.05). Cortisol did not change significantly. Infusion of 1 pmol·kg−1 ·min−1 of angiotensin II produced an elevation of aldosterone (by 186%, p<0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.
Prevention of bone loss by hormone replacement therapy is probably not due to stimulation of calcitonin secretion
Authors: Fletcher C. D. , Farish E. , Leggate J. , Hart D. M.
Published: June 2009

Weekly fasting serum calcitonin levels and biochemical indices of bone metabolism were measured in 13 postmenopausal women being given hormone replacement therapy over a period of 8 weeks. All of the biochemical indices except urinary hydroxyproline creatinine ratios fell significatly, indicating that the treatments were effective in reducing bone turnover. Calcitonin levels fell significantly and, within the individual, levels were positively correlated with adjusted calcium levels. These findings do not support the theory that estrogen conserves bone by stimulating calcitonin secretion.
Urinary luteinizing hormone testing and prediction of ovulation in spontaneous, clomiphene citrate and human menopausal gonadotropin-stimulated cycles. A clinical evaluation
Authors: Martinez Antonio R. , Bernardus Rob E. , Kucharska Danka , Schoemaker Joop
Published: June 2009

A urinary luteinizing hormone test was utilized to predict ovulation in 99 spontaneous, 122 clomiphene citrate, and 82 human menopausal gonadotropin stimulated cycles. Tests were performed in early morning and evening specimens and follicular development was monitored by daily ultrasonography. A positive detection rate of 98, 97, and 94%, respectively, was obtained. Evidence of luteinized unruptured follicles was seen more frequently in stimulated cycles, concurring with negative test results. In 2 spontaneous, 1 clomiphene citrate and 5 hMG induced cycles two distinct LH surges were detected concomitant with a pattern of follicular atresia and subsequent new follicular development. Most ovulations occurred between 16 and 28 h after LH detection, signficantly earlier in spontaneous than in clomiphene citrate stimulated cycles (p<0.02), whereas pre-ovulatory follicles were larger in the clomiphene citrate group (p<0.001). The mean duration of the follicular and luteal phases, as calculated from the LH peak, was substantially shorter in the hMG cycles than in the other two groups (p<0.001).
Age, sex, and serum thyrotropin concentrations in primary hypothyroidism
Authors: Wiener Roberto , Utiger Robert D. , Lew Robert , Emerson Charles H.
Published: June 2009

We studied the relationship between age, sex, serum thyroxine concentrations, and serum thyrotropin concentrations in 202 patients with primary hypothyroidism whose ages ranged from 10 to 89 years. The results from two groups of patients were analysed, both combined and separately, by multiple linear regression analysis of the factors age, sex, group, and serum free T4 index or serum T4 concentration, to predict serum TSH. The serum free T4 index or T4 values and age were negatively correlated with the serum TSH concentrations (p<0.001) for all comparisons. In contrast, there was no significant relationship between sex and serum TSH concentrations in these hypothyroid patients. The age-related decline in serum TSH concentrations in hypothyroidism was apparent during adolescence and early adult life (ages 10 to 39 years) and in elderly subjects (ages 61 to 89 years). We conclude that age is a determinant of TSH secretion independent of the level of thyroid secretion.