bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional stimulation of thyroid epithelial cells in Graves' disease by lymphocytic aggregates and plasma cells
Authors: Paschke Ralf , Brückner Norbert , Eck Thomas , Schaaf Ludwig , Back Walter , Usadel Klaus Henning
Published: June 2009

The significance of intrathyroidal lymphocytic infiltration is not known. However, several indirect lines of evidence suggest that interstitial or intraepithelial lymphocytes are the effector or thyroid autoantibodyproducing lymphocytes in Graves' disease. This has not been investigated in vivo. Changes of nuclear volume of endocrine cells have previously been shown to be a reliable parameter of functional stimulation of endocrine glands. Therefore we investigated this parameter near and off lymphocytic aggregates, loosely distributed plasma cells and memory T cells in paraffine sections of Graves' disease thyroid glands. In 21 Graves' disease thyroid glands we found significant increases of thyroid epithelial cell nuclear volume near plasma cells (198.4 μm3) as well as near lymphocytic aggregates (219.1 μm3) compared with thyroid epithelial cell nuclear volume one microscopic field away (160.1 and 137.7 μm3 respectively). Similar nuclear volume differences were observed after propanolol and thiourelene antithyroid drug treatment. These nuclear volume differences could not be observed in 10 control thyroid glands and around CD45R0-positive memory T cells in Graves' disease thyroid glands. These direct in vivo investigations of regional functional stimulation of thyroid epithelial cells in Graves' disease show local stimulation near lymphocytic aggregates and diffusely distributed plasma cells. Therefore our in vivo data do not permit to identify stimulatory lymphocytes only interstitially or intraepithelially as previously suggested.
Results of external pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease
Authors: Vicente A. , Estrada J. , de la Cuerda C. , Astigarraga B. , Marazuela M. , Blanco C. , Lucas T. , Barceló B.
Published: June 2009

Fourteen adult patients (10 females and 4 males; age range 20-60 years) with persistent Cushing's disease after transsphenoidal microsurgery were treated with pituitary irradiation. Supervoltage multiportal administration was employed at a total dose of 50 Gy (±0.65 sd). The interval between microsurgery and pituitary irradiation was less than 6 months in 6 patients and more than 6 months in 8. The pituitary-adrenal axis was evaluated postsurgically, before irradiation and every 6 months thereafter. The remaining anterior pituitary function was simultaneously tested. Remission rates at 12 months and 24 months after radiotherapy were 61 and 70%, respectively. Two patients developed TSH deficiency and another gonadotropin deficiency during the follow-up after radiation. We conclude that pituitary irradiation is the treatment of choice for persistent Cushing's disease after unsuccessful surgery because of its high efficiency and low incidence of adverse reactions when compared with other forms of treatment.
Different binding of stimulatory-type and blocking-type TSH receptor antibody with guinea-pig testis membrane
Authors: Inui T. , Ochi Y. , Hachiya T. , Chen W. , Nakajima Y. , Kajita Y. , Ogura H.
Published: June 2009

A receptor assay using [125I]bTSH-binding to guinea-pig testis membrane was developed. Unlabelled hCG and FSH inhibited [125I]bTSH binding. In patients with Graves' disease and in untreated hyperthyroid patients, almost all long-acting thyroid stimulators and thyroid-stimulating antibodies, respectively did not inhibit [125I]bTSH binding, which on the other hand was inhibited by thyroid stimulation blocking antibodies in patients with primary hypothyroidism. When the inhibitory effect on the binding of [125I]hCG and 125I-synthetic α-subunit peptide (α26-46) of hCG to testis membrane was examined, bTSH resulted in a significant inhibition. However, all three kinds of TSH receptor antibodies had no inhibitory effect. This study demonstrated 1. interaction of α-subunit of TSH and hCG with the testicular receptor; 2. binding of thyroid stimulation-blocking antibody and lack of binding of thyroid-stimulating antibody to the testicular TSH receptor in spite of binding of these TSH receptor antibodies to the thyroidal TSH receptor, and 3. lack of binding of thyroid-stimulating antibody and thyroid stimulation-blocking antibody to the testicular gonadotropin receptor.
Calcitriol receptors in rat thyroid follicular cells (FRTL-5)
Authors: Berg Jens P. , Torjesen Peter A. , Haug Egil
Published: June 2009

The FRTL-5 cell line is widely used as a model for normal thyroid follicular cells. These cells have retained their ability to alter cAMP production, cell proliferation, iodine uptake, and thyroglobulin synthesis in response to thyrotropin. We have previously shown that calcitriol attenuated both basal and TSH stimulated cAMP production dose-dependently in FRTL-5 cells. Cytosol fractions (105000 g, 60 min, 4°C) prepared from FRTL-5 cell homogenates possessed calcitriol-binding components with a sedimentation coefficient of approximately 3.7 S in high salt (0.3 mol/l KCl) sucrose gradients (5–20%). At 4°C, specific binding increased rapidly during the first 4 h and reached a plateau after 8 h. The specific binding (18 h, 4°C) was maximal at a [3H]calcitriol concentration of approximately 0.5 nmol/l. Scatchard analysis of the binding data indicated one single class of high affinity binding sites with Kd = 105±2 pmol/l and Bmax=38.5±4.7 pmol/g cytosol protein (mean ± sd, N=6). In conclusion, our results suggest that the FRTL-5 cells possess functional receptors for calcitriol with the same physicochemical properties as the receptors found in normal rat tissues.
Expression of GH receptor mRNA in regenerating skeletal muscle of normal and hypophysectomized rats. An in situ hybridization study
Authors: Jennische Eva , Andersson Göran L.
Published: June 2009

Expression of growth hormone receptor mRNA was investigated by in situ hybridization in skeletal muscle from normal and hypophysectomized rats during the first seven days of regeneration after ischemic injury. A digoxigenin-labelled RNA probe directed against the extracellular part of the rat GH receptor was used. In both normal and hypophysectomized rats distinct expression of GH receptor mRNA could be demonstrated in the regenerating muscle cells at the myoblast/myotube stage. The GH receptor expression appeared to decline with increasing maturation of the regenerated muscle fibres. In hypophysectomized rats, the regeneration process and the expression of GH receptor mRNA was delayed compared with that in normal animals. It is concluded that growth hormone may affect also the early phase of muscle regeneration in normal animals. To what extent lack of growth hormone contributes to the delayed regeneration observed in the hypophysectomized rats remains to be elucidated.
In situ hybridization histochemistry of mRNAs for hormones and chromogranins in normal pituitary tissue and pituitary adenoma
Authors: Kilár Ferenc , Muhr Carin , Funa Keiko
Published: June 2009

In situ hybridization histochemistry was employed to detect mRNAs of pituitary hormones and chromogranins in normal pituitary gland and pituitary adenomas. Oligonucleotide probes specific to the mRNAs for prolactin, growth hormone, proopiomelanocortin, the α- and •-subunits of the glycoprotein hormones and chromogranins A and B were used in the hybridization experiments. The oligonucleotides of 27 to 51 bases were labelled radioactively with dATP[α-35S] at the 3'-end using terminal deoxynucleotidyl transferase. Positive hybridization reactions were visualized by autoradiography in the normal pituitary gland with all of the probes. The clinically diagnosed pituitary adenomas (prolactinoma, acromegaly, Cushing's disease, FSH-secreting tumour) showed positive hybridization with the corresponding oligonucleotide probes. In some cases positive hybridization was also obtained with other probes, suggesting multihormone-producing character of the tumour cells. A microprolactinoma was found in a pituitary gland obtained from a patient without any known pituitary disorders. Examination of mRNAs for chromogranin A and B revealed that the normal pituitary gland contains a larger number of cells expressing chromogranin B and a lower number expressing chromogranin A and, moreover, the microprolactinoma lacked the expression of mRNA for chromogranin A but expressed that of chromogranin B.
Prolactin responses to vasoactive intestinal polypeptide and thyrotropin releasing hormone in chronic renal failure
Authors: Arnaout Mohammed A. , Hamzeh Yousef S. , Ajlouni Kamel M.
Published: June 2009

Prolactin response to iv bolus injection of 1 μg/kg vasoactive intestinal polypeptide was determined in 8 patients with chronic renal failure undergoing chronic hemodialysis and in 8 normal controls, age- and sexmatched. Plasma prolactin in the patients showed a blunted response following vasoactive intestinal polypeptide injection, whereas the controls showed significantly higher mean peak prolactin value over the baseline value (p<0.002). The net rise (peak levels minus basal levels) in plasma prolactin and area under the curve after vasoactive active intestinal polypeptide injection in the controls were significantly greater than those in the patients (p<0.001). On a separate day, each individual underwent a TRH (500 μg) challenge with the prolactin response determined. The patients had significantly higher peak prolactin values over baseline levels (p<0.02) which, however, were not significantly different from those in the control group. In the patients, the peak net prolactin increments and area under the curve were significantly higher following TRH than following vasoactive intestinal polypeptide (p<0.05). The net prolactin increments to TRH challenge were significantly higher in the control group than in the patients (p<0.001). The results demonstrate the blunted prolactin response to the stimulatory effect of vasoactive intestinal polypeptide and TRH in chronic renal failure. In chronic renal failure prolactin release after vasoactive intestinal polypeptide is more blunted than after TRH. These data suggest that the responsiveness of plasma prolactin to vasoactive intestinal polypeptide is defective in these patients, though the mechanism(s) are yet to be defined.
Serum levels of intact parathyroid hormone in elderly patients with hip fracture living at home
Authors: Falch Jan A , Mowé Morten , Bøhmer Thomas , Haug Egil
Published: June 2009

The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7±15.9 vs 46.0±27.8 nmol/l) and calcitriol (63.6±25.0 vs 91.1±39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (47.2±2.1 vs 5.3±3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture.
High-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy
Authors: Antonelli Alessandro , Saracino Antonella , Alberti Baldassare , Canapicchi Raffaello , Cartei Francesco , Lepri Antonio , Laddaga Michele , Baschieri Lidio
Published: June 2009

We have evaluated the efficacy of high-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy, and have carried out a prospective randomized clinical trial, including a single-blind evaluation, whereby 14 patients were assigned to two different treatment groups: 7 patients were treated with intravenous immunoglobulin and orbital radiotherapy (Group 1) and 7 patients were given intravenous immunoglobulin alone (Group 2). The results of the intravenous immunoglobulin treatment were also compared with those obtained in a Historical Control Group (12 patients) treated with systemic methylprednisolone and orbital irradiation. Degree of ocular involvement and response to treatment were assessed by ophthalmopathy index. The mean initial and final ophthalmopathy index showed no significant difference among the three groups. Comparison between the mean initial and final ophthalmopathy index showed a statistically significant reduction (p<0.005) in all three groups, the observed changes being confirmed by orbital computerized tomography in Groups 1 and 2. Corticosteroid treatment was associated with major and minor side effects, while no important adverse reactions were observed during intravenous immunoglobulin treatment. Even considering our results as preliminary, we conclude that intravenous immunoglobulin treatment is effective and safe in improving Graves' ophthalmopathy.
Neonatal ovariectomy and pituitary-adrenal responsiveness in the adult rat
Authors: Fitch Roslyn H , McGivern Robert F , Redei Eva , Schrott Lisa M , Cowell Patricia E , Denenberg Victor H
Published: June 2009

Litters of female rat pups were handled daily from birth to weaning. When 12 days old the pups were ovariectomized or received sham surgery. At 70 days sham and ovariectomized animals were decapitated immediately or placed within a novel environment for 10, 20, or 40 min before decapitation. Basal plasma levels of androstenedione in ovariectomized animals were approximately half that of intact sham controls, and stress caused only a small rise in androstenedione in this group. Androstenedione levels in ovariectomized animals were consistently at or below the lower sensitivity of the radioimmunoassay, indicating that circulating levels of androstenedione in the female rat are primarily of ovarian origin. Basal ACTH and corticosterone levels did not differ significantly between the two groups. However, stress-induced levels of ACTH and corticosterone were significantly depressed in ovariectomized subjects compared to controls following exposure to the novel environment. Furthermore, while ACTH levels started to return to baseline by 40 min in controls, this effect was not observed in ovariectomized animals. These findings demonstrate that prepubertal removal of ovarian humoral factors can have a long-term impact on the responsiveness of the hypothalamic-pituitary-adrenal axis to stress.
The plateau phase rat goiter contains a sub-population of TSH-responsive follicular cells capable of proliferation following transplantation
Authors: Groch Kevin M , Clifton Kelly H
Published: June 2009

In the rat, chronic TSH stimulation leads to self-limited thyroid hyperplasia, goitrogenesis, and TSH-responsive thyroid tumors. The current studies were aimed at clarifying the mechanism by which hormone-responsive, proliferating follicular cells arise in quiescent plateau phase rat goiters. Enzymatically monodispersed rat thyrocytes from early plateau phase and involuting goiters were analyzed for the capacity to form thyroid follicular units after transplantation into syngeneic recipients. Goiters induced with two different regimens contained substantial numbers of cells capable of proliferating into functioning thyroid follicular tissue after transplantation. The clonogenic fractions of cells from goiters induced by 3-amino-1,2,4-triazole or KClO4/Remington low iodine diet were significantly lower than that of cells from control glands. Furthermore, the clonogenic fraction of cells from the KClO4 goiters was also found to be significantly less than that of cells from aminotriazole goiters despite similar TSH levels in the cell donors. The hormone responsiveness of the clonogenic goiter cells and the histological appearance and functional capacity of the thyroid tissue which arose after grafting were indistinguishable from controls. We conclude that the capacity to clonally proliferate into follicular units is a specific trait which characterizes a unique subset of follicular cells and speculate that the hormone-responsive tumors which typically appear in the chronically stimulated rat thyroid originate from cells within this subset.
GH response to GHRH, insulin, clonidine and arginine after GHRH pretreatment in children
Authors: Bernasconi Sergio , Volta Cecilia , Cozzini Antonella , Ziveri Mariangela , Ghizzoni Lucia , Panza Costantino , Ghigo Ezio
Published: June 2009

To determine whether differences in the neuroendocrine control of GH are present between children and adult subjects, the GH response to GHRH (1 μg/kg) (group 1), insulin-induced hypoglycemia (0.1 U/kg iv) (group 2), clonidine (150 μg/m2 po) (group 3) and iv arginine (0.5 g/kg in 30 min) (group 4) after GHRH pretreatment (1 μg/kg) was studied in 26 short-stature normal children (mean age 10.2 years). The results were compared with historical data in adults. No differences were present among mean peak GH levels after the first and second stimuli in groups 1, 2 and 3, while in group 4 the GH response to arginine administration was lower than that obtained after the initial GHRH (0.43±0.04 vs 0.9±0.13 nmol/l). Moreover, comparing the GH peak values following the second stimulus, it appears that the greatest GH responses were elicited by GHRH (1.31±0.23 nmol/l) and clonidine (1.11±0.22 nmol/l), while the lowest was elicited by arginine (0.43±0.04 nmol/l). In adults, sequential GHRH administration leads to inhibition of the response of the somatotropes, probably mediated by an increase in hypothalamic somatostatin. Our results confirm that after GHRH prestimulation GHRH elicits a significant GH response suggesting that activation of the somatostatinergic tone is less effective in children. This hypothesis also explains the low GH response to arginine which acts selectively through somatostatin inhibition.
Metformin ameliorates extreme insulin resistance in a patient with anti-insulin receptor antibodies: description of insulin receptor and postreceptor effects in vivo and in vitro
Authors: Paolo Salvatore Di
Published: June 2009

The effect of metformin on insulin binding and insulin action in the presence of anti-insulin receptor antibodies was investigated in a case of type B extreme insulin resistance. Oral administration of metformin (1 500 mg/d) for 10 days significantly decreased plasma blood glucose and insulin levels and enhanced the hypoglycemic response to exogenous insulin. In vitro preincubation of normal erythrocytes with insulin receptor antibody from the patient plus 4× 10−5 mol/l metformin markedly enhanced insulin binding to receptors, compared to cells incubated with antibody alone. This effect was apparent after 2 h, was maximal after 4 h and did not change up to 24 h. Closely similar results were found when human adipocytes were studied. Analysis of binding data confirmed the increase in both receptor number and affinity. One hour exposure of control adipocytes to metformin enhanced basal lipogenesis by more than 30%. Acute exposure of fat cells to the patient's receptor antibodies resulted in a stimulation of glucose transport and a state of severe insulin resistance. The addition of metformin to antibody in preincubation buffer strongly enhanced basal glucose incorporation into lipids, but did not prevent insulin unresponsiveness. It is suggested that metformin increases, possibly through a change in the spatial conformation of insulin receptor within the plasma membrane, the availability of preexisting receptors to insulin binding and/or decreases the availability of specific epitopes to antibody anchoring. Further, in the model of insulin resistance described here, metformin enhanced the basal rate of glucose transport through a direct insulin-mimicking activity and/or a potentiation of the sensitivity of glucose transport to the antibody.
Persistence of hyperinsulinemia in polycystic ovary syndrome after ovarian suppression by gonadotropin-releasing hormone agonist
Authors: Dale Per Olav , Tanbo Tom , Djøseland Ole , Jervell Jak , Åbyholm Thomas
Published: June 2009

To investigate the effect of long-term androgen suppression on insulin sensitivity, obese and non-obese women with the polycystic ovary syndrome and obese and non-obese ovulatory women were given an oral glucose tolerance test before and after treatment with a gonadotropin-releasing hormone agonist. The women with polycystic ovary syndrome showed higher basal luteinizing hormone and androgen levels than the ovulatory women. All women with the polycystic ovary syndrome responded non-diabetically to the glucose tolerance test. However, compared with controls, the obese women with the polycystic ovary syndrome showed a hyperinsulinemic response to the glucose tolerance test, indicating insulin resistance. During the 3-h glucose tolerance test there was no concomitant change in androgen levels in the hyperinsulinemic women with the polycystic ovary syndrome. The insulin response to an oral glucose tolerance test remained unchanged in all women, although a hypogonadotropic hypogonadal state was maintained for several weeks. This study therefore suggests that endogenous androgens do not play a role in sustaining insulin resistance in women with the polycystic ovary syndrome.
5-α androstane diol stimulates the pituitary growth hormone responsiveness to growth hormone releasing hormone more effectively than testosterone or dihydrotestosterone in rats
Authors: Aguilar E , Tena-Sempere M , Pinilla L
Published: June 2009

The effect of different androgens and estradiol on pituitary responsiveness to growth hormone releasing hormone was studied in intact and orchidectomized adult male Wistar rats, by injecting subcutaneously immediately after orchidectomy for two weeks with testosterone, dihydrotestosterone, 5-α androstane, 3-α, 17 β-diol or estradiol dissolved in olive oil (in doses of 0.2 or 2.0 mg·kg−1·day−1) or vehicle. Pituitary responsiveness was tested in pentobarbital anaesthetized rats by measuring growth hormone plasma levels at different times after administration of growth hormone releasing hormone (1-29) NH2. We found that: (a) High doses of testosterone, dihydrotestosterone and 5-α androstane, 3α, 1 7 β-diol restored gonadotropin plasma concentrations and organ weights altered by orchidectomy; (b) both pituitary growth hormone content and concentration remained unaffected after orchidectomy or androgen replacement and decreased significantly after estradiol injection; (c) orchidectomy significantly reduced growth hormone-stimulated growth hormone releasing hormone secretion; (d) treatment with 5-α androstane, 3-α, 1 7 β-diol increased more than testosterone or dihydrotestosterone both the peak concentration and the mean growth hormone secretion after growth hormone releasing hormone stimulation: (e) no differences were observed in the treatment with testosterone or dihydrotestosterone; (f) estradiol given at a dose of 0.2 mg·kg−1·day−1 increased pituitary responsiveness to growth hormone releasing hormone. These results demonstrated that testosterone and 5-α androstane, 3-α, 17 β-diol, which do not differ in their action on pituitary growth hormone content, increased the pituitary responsiveness to growth hormone releasing hormone differently and that the low pituitary responsiveness to growth hormone releasing hormone previously described in prepubertal animals was not due mainly to the secretion of 5-α androstane, 3-α, 1 7 β-diol.
Dramatic response of a metastatic carcinoid tumour to a combination of interferon and octreotide
Authors: Joensuu Heikki , Kätkä Kalevi , Kujari Harry
Published: June 2009

The combination of alpha-interferon and octreotide has rarely been tested in the treatment of carcinoid syndrome. We describe a patient who was moribund when treated with interferon alone, but enjoyed a dramatic response leading to disappearance of all symptoms, normalization of dU-5-HIAA, and restoration of his normal life-style when octreotide was initiated. Neither interferon nor octreotide could be withdrawn without reappearance of the symptoms, suggesting that the combination of alpha-interferon and octreotide may have synergistic effects in carcinoid syndrome.
Inhibition by ethanol of the oxytocin response to breast stimulation in normal women and the role of endogenous opioids
Authors: Coiro V , Alboni A , Gramellini D , Cigarini C , Bianconi L , Pignatti D , Volpi R , Chiodera P
Published: June 2009

The possible inhibition exerted by ethanol on the oxytocin response to breast stimulation was tested in normal women. The possible role of endogenous opioids in the control of the oxytocin response to breast stimulation and/or ethanol action was also examined. Sixteen normal women were tested four times on the 22nd day of four consecutive regular menstrual cycles. All women underwent mechanical breast stimulation (for 10 min) with the concomitant administration of normal saline, naloxone (2 or 4 mg in an iv bolus plus 5 or 10 mg over 16 min), ethanol (50 ml in 110ml of whisky po) or the combination of ethanol and naloxone. Plasma oxytocin levels rose about twofold after breast stimulation, with a mean peak response at 10 min. The oxytocin response to breast stimulation was not changed by the treatment with the lower (2 plus 5 mg) or the higher (4 plus 10 mg) dose of naloxone, whereas it was completely abolished by ethanol. However, when ethanol was given together with naloxone, the oxytocin rise induced by breast stimulation was only partially inhibited by ethanol (the mean oxytocin peak was 50% higher than baseline). At both doses naloxone produced similar effects. These data demonstrate that ethanol inhibits the oxytocin response to breast stimulation. Naloxone sensitive endogenous opioids do not appear to be involved in the control of the oxytocin rise induced by breast stimulation. In contrast, since naloxone partially reversed the inhibiting effects of ethanol, a partial involvement of opioid peptides in ethanol action is supposed.
Immunoreactive plasma inhibin levels in men after polyvalent chemotherapy of germinal cell cancer
Authors: Brennemann W , Stoffel-Wagner B , Bidlingmaier F , Klingmüller D
Published: June 2009

In vitro studies have shown that the Sertoli cell is the primary source of inhibin in the male. We measured immunoreactive inhibin with a new two-site immunoenzymatic assay in the plasma of 92 men: 40 normal men, 7 patients with germinal cell cancer after unilateral orchidectomy and 45 patients with the same disease following unilateral orchidectomy and subsequent chemotherapy based on cisplatin. Normal men had inhibin levels of 1.77±0.09 U/l × 10−3 (mean±sem). Seven patients after unilateral orchidectomy had inhibin concentrations within the lower normal range (1.23±0.22 U/l × 10−3). Forty-five patients were investigated in a cross-sectional study up to 102 months after completion of chemotherapy. Inhibin levels were within the normal range in 25 patients (1.76±0.114 U/l × 10−3); 18 patients had significantly lower inhibin levels (0.48±0.05 U/l × 10−3, p<0.005) when compared to patients after unilateral orchidectomy. Two patients had elevated inhibin levels (4.4 and 5.6 U/l × 10−3). The proportion of patients with normal and subnormal inhibin was not dependent on the time that elapsed after completion of chemotherapy or on the chemotherapy combination. There was no correlation between immunoreactive plasma inhibin and LH, FSH, testosterone or sperm count. The decrease in inhibin concentrations after chemotherapy may indicate long-term damage to Sertoli cells in some of the patients.
Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man
Authors: Oturai Peter S , Friberg Lars , Sam Ian , Perrild Hans
Published: June 2009

To assess the regional changes in cerebral blood flow, 10 healthy volunteers were given 400 μg thyrotropin-releasing hormone iv in a double-blind, randomized, cross-over study. Regional cerebral blood flow was determined simultaneously in two slices of the brain, using a single photon emission computerized tomograph and inhalation of 133Xe. Thyrotropin-releasing hormone caused a significant mean increase of 3.7% (range −8.8–22.7) in blood flow in a region consistent with the left thalamus compared to placebo (3.2% decrease). In 25 other regions no significant change was detected. The thalamic region has previously been shown to be a region especially affected by thyrotropin-releasing hormone in animal studies. The thyrotropin-releasing hormone injection was followed by a minor rise in systemic blood pressure, but not a rise that could affect the cerebral blood flow. The effect of thyrotropin-releasing hormone on the regional cerebral blood flow in the thalamic region was much lower compared to changes found in sedated animals given a hundredfold higher dose of thyrotropin-releasing hormone.
Reversible primary hypothyroidism and elevated serum iodine level in patients with renal dysfunction
Authors: Sato Kaori , Okamura Ken , Yoshinari Mototaka , Kuroda Takeo , Ikenoue Hiroshi , Okazawa Kaeko , Mizokami Tetsuya , Onoyama Kaoru , Fujishima Masatoshi
Published: June 2009

Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH >10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen >7.1 mmol/l and creatinine >106 μmol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30(83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67–15591 μg/l, N=19) and a high thyroidal radioactive iodine uptake (51.5±29.3%at24h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.
Comparative value of plasma ACTH and beta-endorphin measurement with three different commercial kits for the etiological diagnosis of ACTH-dependent Cushing's syndrome
Authors: Tabarin A , Corcuff JB , Rashedi M , Navarranne A , Ducassou D , Roger P
Published: June 2009

Recent reports suggest that, contrary to radioimmunoassays (RIA), immunoradiometric assays (IRMA) artifactually decrease plasma ACTH levels in patients with the ectopic ACTH syndrome. Discrepancies between RIA and IRMA results may provide a means of discriminating this entity from Cushing's disease. We have compared the results of these two techniques, together with those of a β-endorphin assay, in 1 7 patients with Cushing's disease, 9 with the ectopic ACTH syndrome and 30 controls. ACTH-RIA and ACTH-IRMA levels in patients with Cushing's disease were similar (17.5±2.5 vs 15.1±2.8 pmol/l) and were correlated (rs=0.59, p<0.01). ACTH-RIA levels in patients with the ectopic ACTH syndrome were higher than ACTH-IRMA levels (27.3±2.9 vs 14.5±2.5, p<0.01) and these did not correlate. The ACTH-RIA and ACTH-RIA/ACTH-IRMA ratio levels in patients with the ectopic ACTH syndrome were higher than those of patients with Cushing's disease (p<0.01), but they overlapped with these in 27 and 31% of cases respectively. Plasma β-endorphin level was higher in patients with the ectopic ACTH syndrome than in patients with Cushing's disease (81.9±19.4 vs 26.4±5.6 pmol/l, p <0.01) and was correlated with ACTH only in patients with Cushing's disease. The overlap in β-endorphin and β-endorphin/ACTH-IRMA molar ratio levels between the two groups were 19 and 27% respectively. Although no parameter could be used to make clearcut distinction between Cushing's disease and the ectopic ACTH syndrome, the discriminative power of β-endorphin level was clearly better than that of the comparison between ACTH-RIA and ACTH-IRMA levels.
Increase in T3 levels during hypocorticism in patients with chronic secondary adrenocortical insufficiency
Authors: Comtois Ronald , Hébert Josée , Soucy Jean-Paul
Published: June 2009

The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the medical literature. This study was designed to determine the clinical and laboratory features suggesting the diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states. Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and differential white blood cell count. However, serum T4 was lower (65±19 vs 95±21 nmol/l, p< 0.001) during cortisol deficiency, while T3 was higher (2.4±0.67 vs 2.0±0.60 nmol/l, p<0.001). Furthermore, rT3 decreased significantly during hypocorticism (0.27±0.07 vs 0.18±0.07 nmol/l, p<0.001). TheT4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29±12.5 vs 57±9.4, p<0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the increased peripheral conversion of T4 to T3 during cortisol deficiency.
Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production
Authors: Tremollieres Florence A , Strong Donna D , Baylink David J , Mohan Subburaman
Published: June 2009

Recent clinical studies suggest that progesterone may be involved in the regulation of bone turnover and could promote bone formation. This study was undertaken to evaluate whether progesterone and promegestone (a 19 nor-PG derivative) may have a direct effect on human bone cells and, if so, whether growth factor production could be involved in promoting this effect. The osteosarcoma cell line TE85 and untransformed normal human osteoblastic cells derived from iliac crest were used as in vitro model systems. Progesterone and promegestone were found to significantly increase [3H]thymidine incorporation in TE8 5 cells in a dose-dependent manner at concentrations ranging from 10−12to 10−8 mol/l after four days of cultivation (p<0.01, ANOVA). Consistent with this response in the TE85 cells, progesterone and promegestone increased cell number in human osteoblastic cells after six days of treatment (p<0.05. ANOVA). To determine whether this effect on cell proliferation was mediated by the insulin-like growth factor (IGF) regulatory system, the levels of IGF-1, IGF-2 and IGF binding protein (IGFBP) were measured in the conditioned media of both TE85 and human osteoblast cells. While no significant changes in IGF-1 levels were found in the conditioned media of progesterone and promegestone treated cultures, progesterone and promegestone at the concentration of 5 nmol/l significantly increased IGF-2 levels 2.4 and 1.5-fold respectively, at 48 h in the conditioned medium of TE8 5 cells as compared to control. Similarly, a 4.1 and 1.9-fold increase in IGF-2 levels was found upon treatment with progesterone and promegestone in human osteoblastic cells. Consistent with the increased secretion of IGF-2 into the conditioned medium, IGF-2 mRNA levels were found to be increased in TE85 cells. A 4.9 kb transcript was increased 2.7 and 3.7-fold respectively after 6 h of exposure to 5 nmol/l of progesterone and promegestone as compared to control. Western ligand blot analysis of conditioned medium collected from TE85 and human osteoblast cell cultures treated with progesterone and promegestone revealed no changes in the levels of IGFBP-3 and IGFBP-4 after 48 h of treatment. Consistent with these results, the IGFBP-4 mRNA level was unaffected. These data suggest that both progesterone and promegestone stimulate human bone cell proliferation and that the mechanism may in part involve increased IGF-2 secretion. Because IGF-2 has been proposed to play a potential role in the coupling of bone formation to bone resorption, it follows that progesterone deficiency may be involved in the uncoupling that occurs in postmenopause. In any case, the findings that progesterone and promegestone have direct effects on bone formation could have physiological implications.
Direct effects of bromocriptine on the steroidogenic capability of porcine granulosa cells
Authors: Kamada Shusaku , Kubota Toshiro , Taguchi Makoto , Aso Takeshi
Published: June 2009

The direct effects of bromocriptine on steroidogenesis were examined in cultured porcine granulosa cells. The following observations were made with bromocriptine: (1) It significantly increased the basal or FSH-stimulated secretion of progesterone in cultured porcine granulosa cells at concentrations exceeding 10−7 mol/l; (2) its inhibitory effect on basal estradiol secretion was demonstrated; (3) it did not influence cell number in cultured porcine granulosa cells; (4) it increased the extracellular accumulation of cAMP in a concentration-dependent manner; and (5) it did not induce a change in cytosolic free Ca2+ concentration. These findings suggest that bromocriptine exerts a direct effect on steroidogenesis in ovarian granulosa cells.
Immunoreactive ACTH in the cerebrospinal fluid of the rat: decrease after mediobasal hypothalamic lesion and hypophysectomy, increase after adrenalectomy
Authors: Barna István
Published: June 2009

The effect of various anaesthetics and of the manipulations of the hypothalamo-pituitary-adrenocortical system (hypophysectomy, adrenalectomy and lesion of the mediobasal hypothalamus) was studied on immunoreactive-ACTH levels in the plasma and in the cerebrospinal fluid in the rat. The anaesthetics used (Hypnorm. pentobarbital, urethan and Ketanest) were without effect on immunoreactive-ACTH concentration in the cerebrospinal fluid. Immunoreactive-ACTH was significantly decreased after hypophysectomy and elevated after adrenalectomy in both cerebrospinal fluid and plasma. Destruction of the mediobasal hypothalamus resulted in reduced immunoreactive-ACTH content in the cerebrospinal fluid (about 20% of control) in both experiments, whereas immunoreactive-ACTH levels in the plasma of the lesioned rats were lower only in one of the two experiments performed. These data suggest that the main source of the immunoreactive-ACTH in the cerebrospinal fluid of the rat is the hypothalamus: the contribution of the pituitary gland being less than 50% of the radioimmunoassayable ACTH.
Thyroid hormone responsiveness of the L1210 murine leukemia cell line
Authors: Brtko J , Filipčík P , Knopp J , Sedláková V ,   L' Rauová
Published: June 2009

The presence of saturable and high affinity 3,5,3′-triiodothyronine (T3) binding sites was demonstrated in LI 210 murine leukemia cell nuclei. Scatchard analysis revealed one class of receptors for T3 with Ka = 2.187 × 109l/mol and a maximum binding capacity (Bmax) of 3.96 fmol/106 cells. The effects of T3 on protein phosphorylation and growth rate of L1210 cells were investigated in a medium containing T3-depleted fetal calf serum. T3 was observed to be effective in enhancing protein phosphorylation (153.06%±5.99 sd) compared to cells grown in the absence of T3 (81.49%±13.50 sd). Moreover, in the presence of high T3 concentration (11.15 nmol/l) T3 was found to significantly increase the cell growth rate. In addition, the T3 receptor-associated alterations during the cell cycle, as measured by flow cytometry, suggest that the presence of T3 receptors becomes evident during the late G3 phase of the cell cycle, and T3 receptor numbers increase during the S phase. These results suggest that in in vitro conditions representing high T3 concentration, the number of L1210 leukemia cells may be increased by T3 via nuclear receptors. The L1210 leukemia cell line may serve as a convenient tool for in vitro studies of nuclear receptors and/or mechanism of action of T3. The binding affinity of T3 receptors is similar to that found in rat hepatocytes or human lymphocytes.
Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism
Authors: Degerblad Marie , Elgindy Nabil , Hall Kerstin , Sjöberg Hans-Erik , Thorén Marja
Published: June 2009

Six patients (21–50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatropin, 0.04–0.1 U·kg·body wt−1·day−1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0±0.6 (sem)% and 3.8±1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were −2.4±0.6% and −1.9±0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean + 2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.
Humoral immunity and retrobulbar fibroblasts in endocrine ophthalmopathy
Authors: Stover C , Otto E , Beyer J , Kahaly G
Published: June 2009

The exact role of retrobulbar fibroblasts in the immunopathogenesis of endocrine ophthalmopathy still remains to be elucidated. To evaluate the in vitro influence of humoral immunity on retrobulbar fibroblasts, the effects of immunoglobulin G as well as of the sera of 50 euthyroid patients with endocrine ophthalmopathy and 30 controls on both porcine and human (patients' and controls') retrobulbar fibroblasts were measured by means of several assays: a colorimetric test involving a heterocyclic chemical, a tetrazolium bromide, was applied to quantify the activity of mitochondrial dehydrogenases; the incorporation of 3H-thymidine was determined as a sensitive parameter for cell proliferation, and an enzyme-linked immunosorbent assay was to reveal specific binding of antibodies to the cells. There was consistently no significant difference between patients' (untreated or treated) and controls' IgG to bind to, to activate or to stimulate the proliferation of porcine and human (patients and controls) retrobulbar fibroblasts. The effects of patients' heat-inactivated and non-inactivated sera were indistinguishable from those of the controls. Incubation of autologous sera, however, led to an activation of retrobulbar fibroblasts which was both higher than the median caused by the patients' group and that engendered by incubation of autologous IgG. Yet, a significant role that humoral immunity might play directly on retrobulbar fibroblasts could not be detected in the experiments conducted in this study.
An investigation of LH pulsatility in burned men by bioassay and radioimmunoassay
Authors: Semple CG , Mitchell R , Hollis S , Robertson WR
Published: June 2009

LH pulsatility studies were performed in six burned patients by removing blood samples at 10 min intervals over a 6 h period. All samples were assayed for LH by bioassay (B-LH), LH by radioimmunoassay (I-LH) and testosterone. Mean serum testosterone concentrations of the burned patients were low (6.7±1.6 nmol/l). I-LH levels were lower than B-LH in all samples. Frequency of bioactive or immunoreactive pulses as well as mean B-LH and I-LH concentrations were similar to previously published data from normal men examined in the same laboratory. The mean biological activity of LH (expressed as the ratio of B-LH to I-LH, the B:I ratio) was lower in burned subjects (1.9±0.1) than previously reported in normal men. The B:I ratios of burned men were lower (p <0.01) at pulse peaks than at nadirs (1.8±0.1 vs 2.0±0.1) and an increase in serum testosterone concentration did not follow an LH peak. Serum testosterone concentrations did not cross-correlate with B-LH or I-LH. This contrasts with the findings in normal subjects where the B:I ratios have been found to be higher at pulse peaks than at nadirs and an increase in serum testosterone concentration follows a pulse peak and serum testosterone cross-correlates with B-LH and I-LH. LH secreted in a pulse peak in normal men may contain a particularly biologically potent form of the molecule but this may not be the case in burned men.
Evidence of intrathyroidal accumulation of TSH receptor antibody in Graves' disease
Authors: Sugenoya Akira , Kobayashi Shinya , Kasuga Yoshio , Masuda Hiroyuki , Fujimori Minoru , Komatsu Makoto , Takahashi Shozo , Yokoyama Shiro , Shimizu Tadahiro , Yamada Takashi , Iida Futoshi
Published: June 2009

To clarify the intrathyroidal accumulation of TSH receptor antibody (TR-ab) produced in the thyroid, adrenalin was injected directly into the thyroid artery of patients with Graves' disease during surgery, allowing serial determination of the TR-ab levels in the thyroidal venous blood. Nine surgical patients (3M and 6F) with Graves' disease and receiving anti-thyroid drugs preoperatively for a period of one to four years were enrolled in this study. Comparison between pre- and post-treatment TR-ab levels revealed continuous increments from the pretreatment levels within 15 min of the injection in five (55.6%) of the nine patients. In three of the five patients, TR-ab levels that had been negative before adrenalin injection became positive 1 min after injection. It is assumed that the increase in the TR-ab level is due to adrenalin-induced constriction of the capillaries in the thyroid tissues, resulting in a voluminous flow of the TR-ab retained in the thyroid into the vein. These findings indicate that the TR-ab level in the peripheral blood does not necessarily reflect precisely the abnormal immunological condition in the Graves' thyroid.
The influence of parathyroid hormone-related protein on hepatic IGF-1 production
Authors: Coxam Véronique , Davicco Marie-Jeanne , Durand Denis , Bauchart Dominique , Lefaivre Jacques , Barlet Jean-Pierre
Published: June 2009

Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery. Electromagnetic blood flow probes in the portal vein and hepatic artery allowed continuous measurement of hepatic IGF-1 production. In accordance with a latin square design these calves received iv mesenteric infusion (for 60 min) of calcium (Ca, 0.125 mmol·kg body wt−1), the synthetic human parathyroid hormone-related protein (1–34) fragment (PTHrP, 1 nmol·kg body wt−1), the synthetic analogue [tyr] 34-bovine PTH-(7–34) NH2 (2 nmol·kg body wt −1) and PTHrP (1 nmol ·kg body wt −1) or solvent alone (1.2 ml·kg body wt −1 ). Hypercalcaemia observed following Ca infusion had no significant effect on hepatic IGF-1 production. PTHrP induced a slight but significant increase in plasma Ca and IGF-1 concentrations measured in the hepatic vein, without changing blood flows measured in the hepatic artery and portal vein. Thus PTHrP increased hepatic IGF-1 production (15.1±2.7 nmol·6 h−1·kg body wt−1 vs 4±1.3 nmol·6 h−1·kg body wt−1 in controls; p <0.05). These effects induced by PTHrP were inhibited by the synthetic analogue [tyr]34bPTH-(7–34) NH2.