bluuebunny/crossref_metadata_2025 huggingface dataset:
Two polyclonal antisera to rat luteal LH/CG receptor with different ligand binding inhibition and immunohistochemical receptor detection capabilities
Authors: Lakkakorpi Jouni T. , Keinänen Kari P. , Rajaniemi Hannu J.
Published: June 2009

Polyclonal antisera to a SDS-denatured and partially renatured rat luteal 90 K LH/CG receptor were raised in rabbits, characterized, and their applicability for immunohistochemical location of the receptor examined. The LH/CG receptor was purified by hCG-affinity chromatography and subjected either to a preparative SDS-PAGE or Western blotting. Gel slices containing the SDS-denatured or nitrocellulose strips containing the renatured 90 K LH/CG receptor were used for immunization. The antisera, termed ARS-2 and ARS-3, respectively, possessed similar antibody titres. Both antisera were able to recognize the native, SDS-denatured, and SDS-denatured and reduced forms of the LH/CG receptor on dot blots, but only ARS-3 contained antibodies to the hormone binding site or a region near to it, as it was able to inhibit the hCG binding to the membrane-bound LH/CG receptor in a dilution-dependent manner. Both antisera recognized the receptor-hCG complex, but ARS-2 stained the complex with about 50% less intensity than the free receptor. ARS-3 located the LH/CG receptor distinctly on the luteal cell surfaces in immunohistochemical staining with peroxidase antiperoxidase complex method, but ARS-2, although it possessed similar antibody titre, revealed negligible staining. Thus, the antisera readily recognize the native receptor, but differ in their capability for inhibiting hormone binding. Only ARS-3, produced against the renatured receptor, contains sufficient amounts of antibodies capable of recognizing free and occupied receptors in immunohistochemistry.
In vivo and in vitro inhibition by ketoconazole of ACTH secretion from a human thymic carcinoid tumour
Authors: Steen Reidar Eilif , Kapelrud Helge , Haug Egil , Frey Harald
Published: June 2009

We treated a patient with an ectopic ACTH-producing thymic carcinoid tumour with ketoconazole. The treatment decreased blood levels of ACTH and cortisol and relieved the patient's symptoms. Tumour explants secreted ACTH to the culture medium for at least 11 days. The tumour cells responded to high extracellular K+ concentration with increased ACTH secretion, whereas the hypothalamic ACTH-releasing hormone (CRH) and cortisol had no effect on ACTH secretion. Addition of ketoconazole to the culture medium decreased ACTH secretion showing that ketoconazole had a direct effect on the tumour cells.
Erythrocytes from patients with low serum concentrations of IGF-I have an increase in receptor sites for IGF-I
Authors: Eshet R. , Dux Z. , Silbergeld A. , Koren R. , Klinger B. , Laron Z.
Published: June 2009

The binding characteristics of insulin-like growth factor I on erythrocytes were studied in 11 patients with long-term IGF-I deprivation and low serum IGF-I levels. Six patients had Laron type dwarfism and 5 idiopathic isolated growth hormone deficiency, with a mean (± sem) serum IGF-I level of 6.01±1.01 nmol/l as compared with that in 25 normal controls of 26.35±2.73 nmol/l (p=0.00001). The mean (± sem) [125I]IGF-I specific binding at a concentration of 4×1012 cell/l was 12.11±1.29% for the patient group compared with 8.75±0.62% for the controls (p=0.005). Scatchard analysis showed a curvilinear plot. Using a non-linear curve fit, the mean (± sem) number of high-affinity receptor sites per cell was found to be 7.34±1.80 in the IGF-I-deprived patients and 2.84±0.29 in the controls (p=0.0005). The mean ± sem dissociation constant was found to be 0.33±0.10 nmol/l for the patients and 0.26±0.08 nmol/l for the controls (NS). This study has demonstrated that the low serum concentration of IGF-I in Laron type dwarfism and isolated growth hormone deficiency is associated with an increase in receptor sites for IGF-I on the erythrocytes. The application of this property as a diagnostic aid remains to be established.
Human anterior pituitary response to exogenous arginine vasopressin
Authors: Meller William H. , Lewis David A. , Gehris Timothy L. , Kathol Roger G.
Published: June 2009

The adrenocorticotropin-releasing effect of arginine vasopressin is well known. The effects of AVP on other anterior pituitary hormones remain confusing, with few in vivo human data available. Two human studies of exogenous AVP effects on ACTH, GH, TSH and prolactin are described. In the dosage and route of administration used, AVP was found to be a specific ACTH secretagogue.
Effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and iodide on the thyrotropin-releasing hormone-induced thyrotropin release from superfused rat pituitary fragments
Authors: Szaboles I. , Schultheiss H. , Astier H. , Horster F. A.
Published: June 2009

The effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and potassium iodide were investigated on basal and stimulated thyrotropin release in an in vitro experimental model. Rat pituitary fragments were superfused by Medium-199 with or without T3 (10−7 mol/l), triiodothyroacetic acid (10−8-10−6 mol/l), iopanoic acid (10−7-10−5 mol/l) or potassium iodide (10−7-10−4 mol/l). This was followed by a 6-min pulse of thyrotropin-releasing hormone (10−8 mol/l). TSH was measured in 3-min fractions. The TRH-induced TSH release from the pituitary fragments was inhibited by T3 (10−7 mol/l), by triiodothyroacetic acid (10−7-10−6 mol/l), and by high concentrations of iodide (10−4 or 10−5 mol/l). Iopanoic acid had no significant effect at the concentrations tested. It is assumed that in vitro, and at similar concentrations, the inhibitory effect of triiodothyroacetic acid on the TRH-induced TSH secretion is comparable to that of T3, whereas iopanoic acid may have no direct detectable effect. In contrast, a direct inhibitory effect of inorganic iodide, at least in pharmacological concentrations in vivo, cannot be excluded.
The neuropeptide, head activator, in human placenta and serum from pregnant women
Authors: Sakura Harutake , Aoki Shigeru , Ozawa Takachika , Hashimoto Tadashi , Sakura Naoki
Published: June 2009

The hydra neuropeptide, head activator, was detected in human placenta using radioimmunoassay. The placenta contained 11-68 fmol/g wet weight of head activator. The slope of the inhibition curve by placental extract in radioimmunoassay was identical to that of synthetic head activator. The molecular weight of the major immunoreactive head activator in placental extract corresponded to the synthetic head activator after Bio-Gel P-2 column chromatography. The peak of immunoreactive head activator in the extract emerged at the same retention time as that of the synthetic head activator on reversed-phase high-performance liquid chromatography. Head activator was localized histologically in trophoblasts of placenta by peroxidase-antiperoxidase staining techniques. The head activator staining was inhibited by the excessive synthetic head activator. The serum head activator level during pregnancy ranged from 9 to 31 pmol/l. A positive linear correlation was found between serum head activator content and gestational weeks.
Plasma glucagon and glucose recovery after hypoglycemia: The effect of total autonomic blockade
Authors: Hilsted J. , Frandsen H. , Holst J. J. , Christensen N. J. , Nielsen S. L.
Published: June 2009

The role of the autonomic nervous system in the glucagon response to hypoglycemia has not been fully clarified. We have studied the effect of total pharmacological blockade of the autonomic nervous system (concomitant α- and β- adrenergic blockade with simultaneous atropine injection) and of isolated α-adrenergic blockade on hormonal responses to hypoglycemia and on blood glucose recovery after hypoglycemia in healthy subjetcs. Neither of the pharmacological blockades had any significant effects on plasma glucagon responses to hypoglycemia nor had they any effect on the rate of blood glucose recovery after hypoglycemia. We conclude that the autonomic nervous system has no major influence on the glucagon response to hypoglycemia in healthy man. Changes in autonomic nervous activity are not essential for blood glucose recovery after hypoglycemia in healthy man.
Diurnal variation and left-right distribution of pyroglutamyl peptidase I activity in the rat brain and retina
Authors: Ramirez M. , Sanchez B. , Arechaga G. , Garcia S. , Lardelli P. , Venzon D. , de Gandarias J. M.
Published: June 2009

The thyroliberin and luliberin contents exhibit a diurnal rhythm within the brain and an asymmetrical distribution of both neuropeptides has been demonstrated in the hypothalamus. Since they have been described as substrates of pyroglutamyl peptidase I, this activity was analysed in several rat brain regions and other structures, in order to investigate its putative diurnal variations and changes in relation to the distribution of these neuropeptides and/or other susceptible substrates. Fluorometric activity was assayed in the retina, pituitary gland, superior cervical ganglia, pineal gland, some selected brain regions, and serum of adult male rats at six different time points of a 12:12 h light:dark cycle, using pyroglutamyl-β-naphthylamide as substrate. A significant circadian rhythm was demonstrated in the retina, the hypothalamus, and the intermediate-posterior pituitary lobe. In addition, a small but significant asymmetrical distribution of this activity, at certain time points, was disclosed: The activity was higher in the left than in the right retina at 10 h of the light period, whereas it was predominant in the right side at 01 h of the dark period. Furthermore, the activity was higher in the left anterior than in the right hypothalamic area at 13 and 01 h. These results could be indicative of a role of this enzymatic activity in the control of the functional status of its endogenous substrates.
Oral estradiol-17β raises the level of plasma high-density lipoprotein in menopausal women by slowing down its clearance rate
Authors: Quintão Eder C. R. , Nakandakare Edna , Oliveira Helena C. F. , Rocha Jussara C. , Garcia Roberto C. , de Melo Nilson R.
Published: June 2009

Plasma lipoprotein composition, plasma kinetics of autologous [125I]HDL and the metabolism of iv administered radioactively labelled artificial chylomicrons were studied in postmenopausal women during a control period and after 4 months of oral estradiol-17β treatment (1 mg/m2 body surface per day). Drug treatment significantly raised plasma HDL-cholesterol levels (19%) in the fasting state and total apolipoprotein A-I (16%), but did not interfere with triglyceride, VLDL, LDL or apolipoprotein-B values. As compared with the control period, estradiol-17β administration significantly slowed down plasma [125I]HDL clearance by about 82% and reduced the delipidation index of the injected artificial chylomicrons by 47% as a consequence of impaired plasma lipolytic activity.
Measurement of intact parathyroid hormone in the diagnosis of hyperparathyroidism
Authors: Bergenfelz Anders , Valdermarsson Stig , Ahrén Bo
Published: June 2009

Plasma levels of parathyroid hormone were determined pre-operatively in 27 consecutive patients with clinical and biochemical signs of primary hyperparathyroidism, by the use of one assay recognizing the intact PTH molecule and one assay recognizing the mid-portion of PTH. Plasma levels of mid-molecule PTH were normal in 5 of the patients with primary hyperparathyroidism. In 4 of these patients, plasma levels of intact PTH were raised. Conversely, in 6 patients with primary hyperparathyroidism, intact PTH were normal pre-operatively. In 5 of these cases, plasma levels of mid-molecule PTH were raised. The EDTA infusion test was performed in 6 patients with normal baseline plasma level of intact PTH pre-operatively. The test correctly predicted all the patients in this group who were found to have primary hyperparathyroidism, as well as a patient with normal parathyroid glands found at operation. We conclude that some patients with primary hyperparathyroidism have normal baseline plasma levels of intact PTH. In these patients, plasma levels of mid-molecule PTH and an EDTA infusion test provide further diagnostic information.
Sex-related responses of beta-endorphin, ACTH, GH and PRL to cold exposure in humans
Authors: Gerra G , Volpi R , Delsignore R , Maninetti L , Caccavari R , Vourna S , Maestri D , Chiodera P , Ugolotti G , Coiro V
Published: June 2009

To establish a possible different reaction between the male and the female to short-term exposure to cold, thermal, cardiovascular and pituitary hormonal responses to cold stress were measured in eight normal men and eight women (ages 19–24). The women were eumenorrheic and were tested in the follicular phase. Each subject, lightly clad, was required to remain for 30 min in a room at an ambient temperature of 2 5°C followed by a 30 min period in a cold room at 4°C. A month later, control tests were carried out at a constant 25°C temperature for 1 h in the same subjects. Skin temperature, heart rate, blood pressure and plasma levels of beta-endorphin, ACTH, cortisol, GH and PRL were measured before and after cold exposure in the two groups. Before the test, all examined parameters were similar in the two groups. During cooling, blood pressure rose and pulse rate decreased significantly in the men, but not in the women, whereas skin temperature dropped in both groups. However, after cold exposure skin temperature was significantly lower in the women than in the men. A slight, but not significant increase in beta-endorphin, ACTH, cortisol and GH levels was observed after cooling in the men, whereas the women showed significant increments of these hormones, When values of skin temperature were combined with the differential (after minus before cold test) hormonal values, significant negative correlations were found for beta-endorphin, ACTH, cortisol and GH. As observed by other authors, a significant and peculiar cold-induced decline in plasma PRL levels was observed in the men; by contrast, a slight, but not significant decrement of PRL was found in the women. Control tests at a constant 25°C temperature did not show significant thermal, cardiovascular or hormonal changes in any subject. These data reflect stronger thermal, cardiovascular and PRL responses to cooling in men than in women. On the other hand, the women, but not the men, showed significant cold-stress-induced increments of beta-endorphin, ACTH and GH, suggesting that the more efficient adaptation to cold of the men might be what prevents the stress-induced hormonal changes observed in the women.
Regulation of cell growth, c-myc mRNA, and 1,25-(OH)2 vitamin D3 receptor in C3H/10T1/2 mouse embryo fibroblasts by calcipotriol and 1,25-(OH)2 vitamin D3
Authors: Trydal Torleif , Lillehaug Johan R. , Aksnes Lage , Aarskog Dagfinn
Published: June 2009

Calcipotriol is a synthetic 1,25-(OH)2D3 analogue with high affinity for the 1,25-(OH)2D3 receptor, but with a lower affinity than 1,25-(OH)2D3 for vitamin D binding protein in serum. The inhibitory action of calcipotriol and 1,25-(OH)2D3 on proliferation of C3H/10T1/2 mouse embryo fibroblasts was examined in the non-transformed cell line CI 8 and in the two transformed, tumorigenic cell lines Cl 16 and TPA 482. Upon exposure to 10 nmol/l calcipotriol or 1,25-(OH)2D3, the proliferation of Cl 8 cell line was almost completely suppressed, whereas both hormones had no effect on the cell lines Cl 16 and TPA 482. Calcipotriol was at least as effective as 1,25-(OH)2D3 in inducing up-regulation of the 1,25-(OH)2D3 receptor. Displacement studies showed no difference between calcipotriol and 1,25-(OH)2D3 in the affinity for the receptor present in Cl 8 or Cl 16 cell extracts. Furthermore, the inhibition of cell growth in Cl 8 cells by calcipotriol was not accompanied by any consistent change in the steady-state expression of c-myc mRNA. In conclusion, calcipotriol had potent growth inhibitory effect on the non-transformed cell line similar to 1,25-(OH)2D3. In the transformed cell lines, calcipotriol did not inhibit proliferation despite potent up-regulation of the 1,25-(OH)2D3 receptor.
Cloning strategies for peptide hormone receptors
Authors: Wright Marianne S , Gautvik Vigdis T , Gautvik Kaare M
Published: June 2009

With the advancement in molecular biology in the last decade many receptors have been cloned and the understanding of their mechanism of function has improved proportionally. In addition the concurrent discovery of receptor gene families has been used to design elegant cloning strategies which in turn have facilitated the characterization of new receptors and receptor subtypes. This review covers the most currently used cloning strategies and gives some examples.
Antibodies to orbital tissues in thyroid-associated ophthalmopathy
Authors: Perros Petros , Kendall-Taylor Pat
Published: June 2009

Thyroid-associated ophthalmopathy is thought to be an autoimmune disease affecting the orbit. The precise pathogenetic mechanisms are not known, but extraocular muscle and/or orbital fibroblasts are the likely targets of the autoimmune attack. Sera from 41 normal controls, 79 patients with thyroid-associated ophthalmopathy and 72 patients with other autoimmune diseases were examined for antibodies to cultured orbital fibroblasts and extraocular muscle by enzyme-linked immunosorbent assay. Orbital fibroblast antibody levels varied widely in all subject groups studied, and failed to distinguish patients with thyroid-associated ophthalmopathy from patients with other autoimmune diseases or controls. Eye-muscle binding antibody levels were higher amongst patients with ophthalmopathy compared to normal controls and patients with Graves' hyperthyroidism without clinical evidence of ophthalmopathy. Furthermore, eye-muscle binding antibody levels were found to be particularly high in patients with ophthalmopathy and concurrent dermopathy, and in patients with ophthalmic (euthyroid) Graves' disease.
Endemic goitre in Senegal—thyroid function etiological factors and treatment with oral iodized oil
Authors: Lazarus John H , Parkes Arthur B , John Rhys , N'Diaye Makhtar , Prysor-Jones Suzanne G
Published: June 2009

Endemic goitre and its response to orally administered iodized oil has been studied in seven villages 25–30 km south of Velingara, Eastern Casamance, Senegal. In 502 adults aged > 15 years goitre prevalence was 62% with 18.2% having goitre grade 2 or 3. Mean free T4 (FT4) was 11.9±3.5 (sd) pmol/l and iodine deficiency was confirmed by noting median urinary I of 0.079 μmol/l (14.9 μmol 1/mol creatinine) with elevated free T3 (FT3)FT4 ratios. Serum selenium concentrations were normal. The response to 480 mg of oral iodized oil assessed at 6 and 12 months was characterized by a 35.8% increase in FT4, a 25% decrease in FT3 and a 50% decrease in TSH (all p<0.01) at 12 months associated with a significant decrease in goitre size measured in 70 persons when compared to 65 controls not receiving iodine. Urinary iodine rose from 0.071 μmol/l to 0.189 μmol/l (p <0.01) during this time and no adverse effects on thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) were observed. A variation in goitre prevalence between villages was noted which, in such a small geographical area, suggests that etiological factors in addition to iodine deficiency may be important in goitre pathogenesis. Oral iodized oil administration is an effective treatment for iodine deficiency goitre in the short term.
Twenty-four year spironolactone therapy in an aged patient with aldosterone-producing adenoma
Authors: Takeda R , Yamazaki T , Ito Y , Koshida H , Morise T , Miyamori I , Hashimoto T , Morimoto S
Published: June 2009

A case of primary aldosteronism treated with spironolactone therapy has been followed up for 24 years. This is probably the longest case of spironolactone therapy for primary aldosteronism that has ever been reported. Long-term treatment with spironolactone controlled the hypertension and prevented hypokalemic alkalosis in this patient, without any deleterious effects on steroid biosynthesis. Based on data obtained during dose reduction and subsequent withdrawal of spironolactone, it is suggested that the suppressed plasma renin activity associated with adenoma-induced aldosteronism develops prior to hypokalemia and hypertension.
Effect of simvastatin in patients with Type I (insulin-dependent) diabetes mellitus and hypercholesterolemia
Authors: Kjær Karen , Hangaard Jørgen , Petersen Niels E , Hagen Claus
Published: June 2009

In 10 hypercholesterolemic patients with Type I (insulin-dependent) diabetes, simvastatin 10–40 mg/day was compared to placebo in a randomized, double-blind, cross-over study with treatment periods of 12 weeks. Between each treatment there was a wash-out period of 4 weeks. Compared to placebo, simvastatin reduced total cholesterol by 19% (p<0.001) and low density lipoprotein (LDL) cholesterol by 24% (p<0.001). Simvastatin therapy reduced plasma triglyceride by 8% and increased high density lipoprotein (HDL) cholesterol by 8%, but neither of these alterations was significant (p>0.05). Diabetic control and daily requirement of insulin were not influenced by simvastatin. In six patients, all men, there were no alterations in the concentrations of dehydroepiandrosterone-sulphate, testosterone, estradiol, prolactin, luteinizing hormone or follicle-stimulating hormone, while sex hormone-binding globulin was significantly (19% (p<0.05)) reduced during therapy with simvastatin. Thus, in Type I (insulin-dependent) diabetic patients, simvastatin causes significant reductions in plasma total cholesterol and LDL cholesterol which are similiar in magnitude to those observed in non-diabetics. This favourable effect can be obtained without any concomitant negative influence on glucose regulation or total gonadal steroid hormone concentrations.
Systematic inclusion of clinical and laboratory data improves diagnostic accuracy of fine-needle aspiration biopsy in solitary thyroid nodules
Authors: Ongphiphadhanakul Boonsong , Rajatanavin Rajata , Chiemchanya Surtrong , Chailurkit La-or , Kongsuksai Atana , Ayuthya Wiwatwong Isarangkul Na
Published: June 2009

In this study, we identified clinical and laboratory markers of malignant thyroid nodules and determined whether systematic inclusion of these data could improve diagnostic accuracy of fine-needle aspiration biopsy in solitary thyroid nodules. The patients were 24 men and 105 women who underwent surgical removal of solitary thyroid nodules and had adequate fine-needle aspiration biopsy performed prior to surgery. Including fine-needle aspiration biopsy's diagnosis of suspected of malignancy in the same category as malignancy, the sensitivity and specificity of fine-needle aspiration biopsy were 71.4% and 85.1%, respectively, with an accuracy of 82.2%. Using stepwise linear regression analysis, clinical data, i.e. increasing age, irregular nodule surface, hard consistency of nodule, and high serum thyroglobulin concentration, were associated with an increased risk of malignancy when the cytological result was excluded. When cytology was also considered, male sex, irregular nodule surface and high serum thyroglobulin concentration were found to be associated with an increased risk of malignancy. The diagnostic value of clinical data alone, even in combination with cytology or laboratory data, was inferior to that of fine-needle aspiration biopsy alone. The specificity and accuracy of fine-needle aspiration biopsy could be increased to 98.0% and 90.7%, respectively, whereas its sensitivity was decreased to 64.3% when these variables were considered in combination. Therefore, of fine-needle aspiration biopsy, clinical and laboratory data, fine-needle aspiration biopsy alone has the highest diagnostic value, which can be increased only when both clinical characteristics and serum thyroglobulin concentration are systematically included.
Seasonal variation in the reproductive hormones of male goats
Authors: Grasselli Francesca , Gaiani Rosella , Tamanini Carlo
Published: June 2009

The aim of this work was to study the circannual plasma profiles of LH, PRL, testosterone (T) and estrone sulfate (EIS) in different periods of the year and to characterize the possible variations in LH and PRL release patterns. We also tried to verify a possible relationship between plasma PRL fluctuations and ambient temperature, as well as the influence of an acute stress condition on levels of plasma PRL. Six adult male goats of the Ionica and Alpine breed reared in Southern Italy (40°N lat.) were subjected to frequent samplings (every 1 5 min for 6 h) once a month for a whole year. The blood samples were assayed for plasma concentrations of EIS, LH and PRL by radioimmunoassay, and for T by enzyme-immunoassay. The ambient temperature was recorded on each day of bleeding. Sex steroids and PRL showed marked circannual variations, with the highest levels during the summer (July) and the lowest during the winter-early spring (March). The concentrations of plasma LH did not indicate significant seasonal variations. A positive relationship was observed between plasma levels of PRL and EIS and ambient temperature. The patterns of LH release seemed to change depending on season, but this was not an obvious and common feature in all bucks. The hormone concentrations for plasma PRL profiles seemed to be influenced by an acute stress condition (associated with cannula insertion and handling procedures), with the variations more marked when the plasma levels of PRL were low.
Serum estradiol 17-sulphate and lipid peroxides in late pregnancy
Authors: Honjo Hideo , Tanaka Kazunori , Yasuda Jinsuke , Ohno Yosuke , Kitawaki Jo , Naitoh Kazuo , Ogino Yoshio , Yamamoto Takara , Okada Hiroji , Watanabe Kazuhiro , Yoshizawa Itsuo
Published: June 2009

Estradiol 17-sulphate is readily converted to 2-OH or 4-OH estradiol 17-sulphate. The latter two strongly antagonize lipid peroxidation, which may play certain roles during pregnancy, such as pregnancy-induced hypertension. Serum estradiol 1 7-sulphate during mid and late pregnancy was measured using a direct radioimmunoassay without hydrolysis, and the level increased as pregnancy progressed. The levels in the sixth (20–23 weeks) and tenth months (36–39 weeks) of gestation were 1.42±0.04 nmol/l (mean±sd) and 3.43±1.09 nmol/l, respectively. The maternal venous levels before and at delivery and in the umbilical veins and artery were 3.38±0.83, 3.48±1.53, 4.11±1.40 and 4.30±1.81 nmol/l, respectively. The latter two values were slightly higher than the former two. Estradiol 1 7-sulphate in maternal venous blood began to decrease around delivery. Serum lipid peroxides were measured using the method of Yagi. Estradiol 17-sulphate and lipid peroxides showed a simple regression slope (r= −0.548, p<0.05) during late pregnancy. These results suggest that estradiol 1 7-sulphate may be converted to 2-OH or 4-OH estradiol 1 7-sulphate, which act as lipid peroxide scavengers during pregnancy.
A circadian rhythm in adrenal responsiveness to ACTH is not confirmed by in vitro studies
Authors: West Sandra H , Bassett Jack R
Published: June 2009

From in vitro studies a circadian variation in adrenal gland response to ACTH was observed. Regulation of this circadian rhythm in adrenal responsiveness was localized to the cellular level; involving variation in either receptor density or affinity. In the present study the circadian variation in adrenal gland responsiveness was studied using an in vitro approach. Levels of corticosterone secretion during the active and inactive phases were determined using incubated rat adrenal slices in the presence and absence of submaximal stimulation by the synthetic ACTH peptide, ACTH(1–24). Initially, a circadian difference in adrenal responsiveness appeared to exist in all groups except the betamethasone pretreated. However, data expressed in terms of corticosterone secretion/mg adrenal weight proved to be misleading due to the presence of an apparent circadian pattern in adrenal gland weight; the adrenal glands from animals in the dark being significantly less in weight than those from animals in the light phase. When the data were expressed in terms of actual gland output, no circadian variation in adrenal response to exogenous ACTH(1–24) stimulation was apparent. In conclusion, the present study does not support the concept of a circadian variation in the adrenal response to ACTH(1–24) stimulation resulting from a variation in the responsiveness of the adrenal cells themselves. However, the present study does not preclude the possibility of a circadian variation due to modulation of adrenal responsiveness by humoral factor(s) other than ACTH.
Insulin-like growth factor binding protein-3 in normal pubertal girls
Authors: Wilson Darrell M , Stene Mark A , Killen Joel D , Hammer Lawrence D , Litt Iris F , Hayward Chris , Taylor C Barr
Published: June 2009

IGFBP-3 concentrations rise in the second decade of life. To test the hypothesis that the stage of pubertal development, independent of chronological age, was associated with these increases we measured serum IGFBP-3 concentrations by radioimmunoassay in 324 sixth and seventh grade girls (12.3±0.7 years) at the beginning of a multisite school-based health curriculum. The mean (±sd) serum IGFBP-3 among the 242 girls with complete data was 4.0±0.7mg/l. Pubertal stage was significantly associated with IGFBP-3 (p<0.0001, ANOVA). Mean concentrations rose from 3.5±0.7 mg/l among those with the earliest pubertal stages to 4.2±0.7mg/l among the mature girls. IGF-I and IGFBP-3 concentrations were significantly correlated (Spearman's r=0.43, p<0.0001). After controlling for the association between pubertal development and IGFBP-3 concentrations, only the waist/hip ratio, among the various measures of body composition, was significantly associated with IGFBP-3 concentration (Spearman's r= −0.23, p=0.0002). Likewise, none of the measures of nutrition: intake of total calories, protein, fat and carbohydrate; serum iron; red cell mean corpuscular volume; or cholesterol; were significantly associated with IGFBP-3 concentrations. There was, however, a small, but significant association between IGFBP-3 concentrations and both serum transferrin and blood hemoglobin concentrations. Pubertal stage has a significant impact on IGFBP-3 concentrations and those attempting to utilize IGFBP-3 concentrations during adolescence should be cognizant of the subject's pubertal stage.
C-peptide profiles in patients with non-insulin-dependent diabetes mellitus before and during insulin treatment
Authors: Lindström Torbjörn , Arnqvist Hans J , Ludvigsson Johnny , von Schenck Henning H
Published: June 2009

The objective of the study was to evaluate the effect of insulin treatment on insulin secretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten patients with NIDDM were first investigated while still taking oral hypoglycemic agents, and then randomized to a crossover study with two eight-week periods of insulin treatment (oral treatment having been stopped) given either as mainly intermediate-acting insulin twice daily (2-dose) or as preprandial regular insulin and intermediate-acting insulin at bedtime (4-dose). In the patients treated with oral agents the 24-h C-peptide area under the curve was similar to that in the controls, but the profile was different with a rise at breakfast but with almost absent meal peaks during the rest of the day. Insulin treatment improved glycemic control markedly, lowered urinary C-peptide excretion and the serum C-peptide concentrations being reduced by more than 50%. The shape of the C-peptide profiles was unaltered and there were no significant differences between the two insulin regimens. The decrease in serum C-peptide concentration during insulin treatment correlated with the change in blood glucose. Fasting serum C-peptide concentrations correlated closely with the 24-h C-peptide area under the curve. In conclusion, insulin treatment of NIDDM patients with secondary failure to oral agents greatly reduces the insulin secretion, probably owing to the reduction in blood glucose.
Mechanism of impaired growth hormone secretion in patients with Cushing's disease
Authors: Takahashi Hideo , Bando Hiroshi , Zhang Chenyu , Yamasaki Ryuichi , Saito Shiro
Published: June 2009

The function of the growth hormone-releasing hormone (GHRH)-growth hormone (GH) axis in Cushing's disease was studied by monitoring (a) the GH responses to GHRH loading and L-dopa loading, (b) the GHRH response to L-dopa loading, and (c) the daytime profiles of plasma GH concentration. GH release following GHRH and L-dopa was blunted in patients as compared to that in age-matched control subjects. However, GHRH release following L-dopa was similar in patients and controls. The plasma GH levels in four patients measured every 20 min by a highly sensitive immunoradiometric assay for GH showed pulsatile GH secretion at low levels during the observation period. These results indicate that GHRH release from the hypothalamus is preserved in patients with Cushing's disease, and support the hypothesis that glucocorticoid inhibits GH secretion by altering the hypothalamic somatostatin tone.
Relationship between plasma growth hormone concentration and cellular sodium transport in acromegaly
Authors: Herlitz Hans , Jonsson Olof , Bengtsson Bengt-Åke
Published: June 2009

We investigated the relationship between mean plasma growth hormone (GH) concentration and cellular sodium transport in untreated and treated acromegaly. Seventeen patients (age 55±3 years) with active acromegaly were studied with respect to plasma GH (mean of 24 h GH profile) and erythrocyte electrolyte content as well as transmembrane sodium transport. The patients were reinvestigated two weeks after successful surgery (N=14) and again after one year (N=13). Erythrocyte electrolytes were analyzed by flame photometry and sodium influx and efflux rate constant determined by in vitro incubation using a modified Keyne's formula. In patients with active acromegaly there was a significant positive correlation between IGF-1 and cellular sodium transport, while GH tended to show a negative relationship to the same parameter. After successful treatment, both IGF-1 and GH disclosed a positive relationship to cellular sodium transport. After one year, a significant increase in erythrocyte sodium content was seen in the patients compared to the preoperative situation. In conclusion, if this is a generalized phenomenon the results are compatible with a sodium-retaining effect of GH via stimulation of transmembrane sodium transport. In active acromegaly this may be counteracted by a sodium transport inhibitor giving the reverse relationship between GH and cellular sodium transport.
Effects of thyroid hormones on mitochondrial oxygen consumption in brown adipose tissue and heart from cold-exposed hypothyroid rats
Authors: Cageao LF , Mignone IR , Ricci CR , Brignone CC , Brignone JA , Zaninovich AA
Published: June 2009

The present work measured brown adipose tissue and heart mitochondrial oxygen consumption in hypothyroid rats treated with replacement doses of T3, T4 or T4 plus iopanoic acid and kept at 4°C for 24 h. Heart oxygen consumption in normal, untreated hypothyroid and T4-treated hypothyroid rats was unaffected by cold exposure. In rats treated with T4 plus iopanoic acid, rates of oxygen consumption were normal in those maintained at 4°C as well as in those kept at room temperature, despite serum T3 concentration being significantly decreased. The cold-exposed T3-treated hypothyroid rats showed a marked decrease in oxygen consumption (p<0.02) and α-glycerophosphate dehydrogenase activity, a T3-dependent enzyme. Mitochondrial oxygen consumption in brown fat from normal (p<0.01), T4-(p<0.02) and T4 plus iopanoic acid-treated (p<0.01) rats rose more than twofold in response to cold. In the T3-treated group, oxygen consumption at room temperature was higher (p<0.02) than in any other group at similar temperatures. However, the T3-treated group showed no changes in oxygen consumption in response to cold, perhaps because this group reached the maximal response at room temperature. The untreated and the T3-treated hypothyroid rats (both groups devoid of T4) did not survive at 4°C unless T4 or several-fold replacement amounts of T3 were administered. The data demonstrate the crucial role of T4 in thermogenesis during cold exposure.
Dissociation of cortisol and adrenal androgen secretion in poorly controlled insulin-dependent diabetes mellitus
Authors: Couch RM
Published: June 2009

In acute illness, cortisol secretion increases whereas that of the adrenal androgens, dehydroepiandrosterone and dehydroepiandrosterone sulfate declines. The present study examined if a similar dissociation of cortisol and adrenal androgen secretion occurs in poorly controlled diabetes mellitus. Serum concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone sulfate obtained at 08.00 were compared in 13 post-pubertal diabetics (mean age 18.0 years) in good control (HbA1C<8.0%) and 10 post-pubertal diabetics (mean age 17.0 years) in poor control (HbA1C> 10.0%). Those in poor control had significantly higher serum cortisol (597±94 nmol/l vs 479±208, p < 0.05), lower dehydroepiandrosterone (13.1±5.5 nmol/l vs 25.3±16.9, p<0.025) and lower dehydroepiandrosterone sulfate (4.5±2.4 μmol/l vs 7.0±3.7, p<0.025). The ratios of dehydroepiandrosterone and dehydroepiandrosterone sulfate to cortisol were also significantly lower in those with poor control. It is concluded that poor control of insulin-dependent diabetes mellitus results in a dissociation of cortisol and adrenal androgen secretion.
Parathyroid stimulation after bleeding in man
Authors: Foldes Joseph , Wilson Paulette , Saeed Sheikh M , Buck Karen , Parfitt A Michael , Kleerekoper Michael
Published: June 2009

A role for the PTH-calcium axis in the normal bone-marrow response to bleeding or erythropoietin administration has been demonstrated in rats. We studied 20 autologous blood donors, each donating two units of blood, who served as a human bleeding model. Fifteen patients completed the study. Blood donations were followed by a significant increase in serum intact PTH (2.15±0.67 to 2.81±0.84 pmol/l; p=0.0003) and protein-corrected total calcium (2.43±0.09 to 2.49±0.08 mmol/l; p=0.02). All the individual values remained within the normal range. PTH weakly correlated with the reticulocyte count, but not with the corrected serum calcium. We conclude that moderate bleeding in humans is followed by a physiological increase in serum PTH and calcium.
The effect of chronic and acute changes in plasma composition on vasopressin secretion and cerebrospinal fluid in the rat
Authors: Wells Timothy , Balment Richard J
Published: June 2009

The effects of chronic and acute changes in plasma composition on the osmolality and sodium concentration of cerebrospinal fluid and plasma vasopressin (AVP) concentration have been examined. Chronic elevation of plasma osmolality in three strains of genetically AVP-deflcient rats (Brattleboro and New Zealand hypertensive and normotensive Brattleboro) was associated with increased cerebrospinal fluid osmolality by comparison with AVP-replete controls (Long Evans and New Zealand genetically hypertensive and normotensive rats). The linear correlation between plasma and cerebrospinal fluid osmolality did not reflect a similar relationship between plasma and cerebrospinal fluid sodium concentration. Hypertensive animals exhibited a threefold higher plasma AVP concentration in association with significantly elevated cerebrospinal fluid osmolality by comparison with normotensive controls. Although ip hypertonic saline injection elicited parallel increases in plasma and cerebrospinal fluid osmolality and sodium concentration in both hypertensive and normotensive rats, only in the normotensives did this result in an increase in plasma AVP concentration. These results indicate that cerebrospinal fluid is subject to modest chronic and acute changes in osmolality and sodium concentration which may contribute to the osmotic control of AVP secretion. The disturbed control of vasopressin secretion in hypertensive rats may in part be related to the abnormal cerebrospinal fluid composition in these animals.
Arginine vasotocin binding component in the uterus (shell gland) of the chicken
Authors: Takahashi Tetsuya , Kawashima Mitsuo , Kamiyoshi Michiharu , Tanaka Katuhide
Published: June 2009

The plasma membrane fraction of the uterus of the chicken was found to contain a component that shows specific binding to arginine vasotocin (AVT), arginine vasopressin (AVP) and oxytocin (OT). This binding component possesses a higher affinity to AVT than to AVP or OT, and the affinity to AVT was higher in laying hens than in non-laying hens and immature pullets, while the maximum number of binding sites per mg protein was less in the laying hens. Intramuscular injections of either estradiol-17β, progesterone or testosterone into the immature pullets for six consecutive days caused an increase in the affinity and number of binding sites. The results suggest that AVT receptors are present in the chicken uterus and that their binding properties are affected by ovarian steroid hormones.
Effect of digoxin on the in vitro secretion of renin and angiotensin II/III immunoreactivity by the human adrenal gland
Authors: Pistorello Matteo , Cimolato Margherita , Pedini Francesco , Piovan Donatella , Boscaro Marco , Fallo Francesco
Published: June 2009

Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10−5, but not 10−8 and 10−6 mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10−5 mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10−5 mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells.
Glucose metabolism in embryos of normal and diabetic rats during organogenesis
Authors: Svensson Annika M , Borg LA Håkan , Eriksson Ulf J
Published: June 2009

To investigate whether malformations in the offspring of diabetic rats are related to a disturbed embryonic glucose metabolism, lactate production, lactate content and glucose oxidation in embryos of normal and manifestly diabetic rats were measured in vitro during the period of organogenesis. The embryonic production and content of lactate decreased by 90% between gestational days 10 and 11. On both gestational days the embryos of diabetic rats showed increased lactate production and content compared to the embryos of normal rats. The embryonic oxidation of glucose decreased slightly from gestational day 10 to day 11, and the embryos of diabetic rats exhibited a lower glucose oxidation rate than those of normal rats on both days. The lactate production and content in the embryos increased with increasing concentrations of glucose in the incubation medium, whereas the oxidation of glucose was unaffected by the glucose concentration. The results suggest that the embryonic metabolism of glucose is only marginally affected by changes in the availability of glucose. The lactate production rate was higher and the glucose oxidation rate lower in the embryos of diabetic than in those of normal rats, even when the values for these metabolic variables were normalized to the embryonic DNA content. Thus, a causative role for a disturbance of the glucose metabolism in diabetes-induced embryonic dysmorphogenesis could be envisaged.
Combined treatment with growth hormone and gonadotropin-releasing hormone analogues in children with isolated growth hormone deficiency
Authors: Saggese Giuseppe , Cesaretti Graziano , Andreani Giuliana , Carlotti Carla
Published: June 2009

In subjects with an isolated GH deficiency the inhibition of puberty by GnRH-analogue administration may be attempted to delay the onset, or to prolong the duration, of pubertal maturation in order to improve final height. We report our experience on the matter in 10 subjects (6M, 4F) suffering from isolated GH deficiency with a chronological age ranging from 6.5 to 10.6 years at diagnosis. After a period of 1–5.1 years of GH treatment, GnRH-analogues (long-acting D-Trp-6-GnRH) were added to GH for 12 months, when six subjects were still prepubertal and four in early puberty. During combined therapy, a regression in pubertal development was shown in three out of four children in early puberty, while serum testosterone or estradiol decreased. Height velocity decreased (from 5.23±1.49 (mean±sd) to 4.12±0.67 cm/year; p<0.02), whereas height sd scores for bone age increased (from −0.75±0.42 to −0.47±0.55; p<0.02). During the year of combined therapy, bone age increased only 0.57±0.27 years. The values for predicted height (TW2 and Bayley-Pinneau method) after combined treatment were also higher than those after treatment with GH alone (p<0.02 and p<0.001, respectively). Our preliminary data showed that the addition of GnRH-analogues to GH in subjects with isolated GH deficiency reduces the effect of GH on height velocity, but determines an improvement in statural prognosis, although a proper answer will not be obtained until final height has been achieved.
Effects of prolonged Acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus
Authors: Vaag Allan A , Beck-Nielsen Henning
Published: June 2009

The effect of prolonged treatment with Acipimox on in vivo peripheral insulin sensitivity, and on glucose and lipid metabolism, was investigated in patients with NIDDM in a double-blind study. Twelve NIDDM patients were randomized to treatment with either placebo or Acipimox in pharmacological doses (250 mg×3) for three months. Fasting plasma glucose, insulin, C-peptide and HbA1c concentrations were unaffected after three months of acipimox treatment. However, fasting plasma non-esterifled fatty acid (NEFA) concentrations were twofold elevated after Acipimox treatment (1.34±0.09 vs 0.66±0.09 mmol/l; p<0.05). Despite this, repeated acute Acipimox administration after the three months' treatment period enhanced total insulin-stimulated glucose disposal to the same extent as acute Acipimox administration before the treatment period (367±59 vs 392±66 mg·m−2·min−1, NS; both p<0.05 vs placebo glucose disposal) (267±44 mg·m−2·min−1). In conclusion, insulin resistance or tachyphylaxis towards the effects of Acipimox on insulin stimulated glucose disposal was not induced during prolonged Acipimox treatment. The lack of improvement of blood glucose control in the patients with NIDDM may be due to the demonstrated rebound effect of lipolysis.