bluuebunny/crossref_metadata_2025 huggingface dataset:
Pituitary-dependent effects of estradiol-17-β catecholamine turnover rates, gamma-aminobutyric acid and glutamate concentrations in various hypothalamic and limbic brain structures
Authors: Jarry H. , Elger W. , Düker E. , Wuttke W.
Published: December 2008

Abstract. Estrogens exert many effects in a variety of hypothalamic and mesolimbic structures. Whether the actions of the estrogens are direct or indirect, possibly involving anterior pituitary hormones, is largely unknown. We therefore studied catecholamine turnover rates, gamma-aminobutyric acid and glutamate concentrations in various hypothalamic and mesolimbic structures in estrogen-treated hypophysectomized (hypox) rats and compared the measured parameters with those in sham hypophysectomized (sham) animals. Results clearly demonstrate that many of the effects of estrogen require an intact pituitary. Dopamine turnover rates in hypox rats were significantly reduced in the hypothalamus and the striatum, whereas they increased in the medial septum and medial preoptic area in comparison with sham rats. Norepinephrine turnover rates were reduced in the anterior mediobasal hypothalamus, somatosensory cortex and the nucleus accumbens of hypox animals in comparison with the sham-operated animals. In contrast, norepinephrine turnover was accelerated in the mediocortical amygdala and posterior medial basal hypothalamus of hypox rats. A significant reduction of epinephrine turnover was evident in the nucleus accumbens of hypox rats. Gamma-aminobutyric acid concentrations increased in the medial septum, anterior and posterior part of the mediobasal hypothalamus, but decreased in the mediocortical amygdala of hypox animals. Concentrations of glutamate were also decreased in the mediocortical amygdala in hypox animals. These results indicate that many direct effects of estrogens in the brain are accompanied by indirect effects which require an intact pituitary. Such effects can best be explained by the estrogen-stimulated high blood prolactin levels, but cannot be ruled out that estrogens act in the brain but require high prolactin levels for their action.
Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children
Authors: Bernasconi S. , Petraglia F. , Iughetti L. , Marcellini C. , Lamborghini A. , Facchinetti F. , Genazzani A. R.
Published: December 2008

Abstract. In order to evaluate the secretion of betaendorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 μg/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 ± 1.8 vs 6.0 ± 0.6 pmol/l; mean ± sem). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.
Acute effects of medetomidine, a selective α2-adrenoceptor agonist, on anterior pituitary hormone and cortisol secretion in man
Authors: Kallio Antero , Koulu Markku , Scheinin Harry , Viikari Jorma , Scheinin Mika
Published: December 2008

Abstract. Single iv doses (25, 50 and 100 μg) of medetomidine, a selective α2-adrenoceptor agonist of the imidazole type, were administered to 8 healthy male volunteers in a randomized, double-blind, placebocontrolled study. The concentration of hGH in plasma was powerfully and dose-dependently increased. The plasma level of cortisol was dose-dependently decreased, whereas TSH showed a slight but statistically significant increase. Plasma levels of PRL, FSH and LH were unaffected by the drug. Medetomidine appears to resemble other α2-adrenoceptor agonists, notably clonidine, in its endocrine effects. Its high selectivity and short duration of action make it a suitable tool for studies of the physiology and pharmacology of α2-adrenoceptors in man.
Trypanosome-induced depression of plasma thyroxine Levels in prepubertal and adult female goats
Authors: Mutayoba B. M. , O'hara-Ireri H. B. , Gombe S.
Published: December 2008

Abstract. Changes in plasma T4 levels were investigated in prepubertal and adult female goats during the course of an experimental Trypanosoma congolense infection. A significant decline in the T4 levels was observed within 1 week of trypanosome challenge. The levels remained low up to the end of the 7th weeks when prepubertal goats received a trypanocidal treatment, whereafter the values started to rise to normal pre-infection values. The post-infection plasma T4 values in the untreated adult goats did not return to normal except in one resistant goat which recovered naturally after 16 weeks of the infection. The thyroid glands of chronically infected and untreated adult goats revealed marked atrophy, fibrosis and colloidopathy. It is concluded that trypanosomiasis rapidly impairs thyroid gland function in susceptible animals, but these changes can be reversed by early trypanocidal treatment before marked degenerative changes become evident or following self cure in resistant animals.
A method for selective infusion in the thyroid artery of the rat and mouse
Authors: Johanson Viktor , Ofverholm Torsten , Ericson Lars E.
Published: December 2008

Abstract. A technique for in vivo infusion in the superior thyroid artery in rats and mice was developed and evaluated. The influx catheter is inserted in retrograde direction into the superior carotid artery. The infusate mixed with blood is directed exclusively to the thyroid lobe via the superior thyroid artery. The thyroid isthmus is divided and the other lobe serves as a control. Thyroid ultrastructure was unaltered after infusion for at least 4 h and the follicle cells displayed a normal morphological response to TSH. Electron microscopical autoradiography (125I, [3H]leucine) was performed using 20–80 times less label as compared with iv administration. Infusion of forskolin, a stimulator of adenylate cyclase, increased the intrathyroidal cyclic AMP levels about 10-fold. Infusion of the ionophore monensin yielded typical dilations of Golgi cisternae as well as reduced secretion of newly synthesized protein into the follicle lumen. The arterial infusion technique developed is useful when in vitro methods or systemic administration of sustances are unsuitable. The technique permits selective administration of small amounts of experimental substances to the thyroid in high concentrations.
Primary treatment of macroprolactinomas with Parlodel LAR®
Authors: van 't Verlaat Johanna W. , Lancranjan Ioana , Hendriks Martin J. , Croughs Ronald J. M.
Published: December 2008

Abstract. Five patients, 3 women and 2 men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels ranging from 4.6 to 102 U/I received six monthly injections of 50–100 mg Parlodel LAR®, an injectable long-acting repeatable form of bromocriptine. The following observations were made: 1. Plasma prolactin levels fell dramatically in all patients and values in the normal range were obtained in 3 patients. 2. In all patients, the onset of tumour reduction was visible on CT scans made one week after the first Parlodel LAR injection. After six Parlodel LAR injections, tumour size was reduced by more than 75% in 3 patients and by 50–75% in two patients. 3. Diminished visual acuity (one patient), bitemporal hemianopia (2 patients), and oculomotor and trochlear nerve dysfunction (one patient) were restored to normal after the first Parlodel LAR injection. 4. Hypogonadism normalized in 2 patients and improved in one patient, whereas plasma gonadotropins remained low in the 2 postmenopausal women. In one patient with hypothyroidism and hypocorticism, thyroid and adrenal functions normalized. It is concluded that bromocriptine retard (50–100 mg monthly) is a useful alternative for oral treatment of patients with prolactinomas, especially in those patients with compliance problems on oral bromocriptine therapy.
Detection of corticosteroid binding globulin in parotid fluids: evidence for the presence of both protein-bound and non-protein-bound (free) steroids in uncontaminated saliva
Authors: Chu F. W. , Ekins R. P.
Published: December 2008

Abstract. Corticosteroid binding globulin (CBG) was detected by a specific radioimmunoassay in mixed saliva (25.4 ± 4.0 μg/l, mean ± sem) and in pure, uncontaminated parotid fluids (17.4 ± 2.7 μg/l) at resting flowrates of approximately 500 μl/min and 50 μl/gland per min, respectively. In parotid fluids collected at stimulated flow-rates of between 300–1000 μl/gland per min, CBG could not be detected. This observation suggests the direct flow-rate-dependent transfer/secretion of CBG in saliva. When cortisol was measured (RIA) in dilution experiments in both mixed saliva and parotid fluids using phosphate buffer at pH 7.4 as diluent, a protein-binding effect analogous to that found in plasma samples was observed. However, this effect was abolished if a known CBG inhibitor, phosphate:citrate buffer at pH 4, was used as the diluent in the assay. A bound fraction of cortisol was found in both mixed saliva (14.0 ± 4.0%) and parotid fluid samples (12.3 ± 1.3%) by equilibrium dialysis. These findings appear to contradict the currently accepted notion that specific plasma steroid binding proteins, and hence the protein-bound steroids, are absent in uncontaminated saliva; and that their presence in mixed saliva is the consequence solely of contamination by gingival fluid and/or plasma from mouth or gum abrasions. We conclude that both protein-bound and free steroids are present in uncontaminated saliva and that salivary total and plasma free steroid concentrations are not identical.
Failure to suppress GH secretion after 2 weeks treatment with atropine or propanthelene in diabetics with proliferative retinopathy
Authors: Hyer S. L. , Sharp P. S. , Brooks R. A. , Burrin J. M. , Kohner E. M.
Published: December 2008

Abstract. Complete suppression of GH secretion may halt the development of retinal new vessels in patients with diabetic proliferative retinopathy. We have investigated the effectiveness of two cholinergic antagonists, atropine and propanthelene given orally for 2 weeks, in suppressing 24-h GH and IGF-I levels. Seven insulin-dependent diabetics (3 males, 4 females; aged 22–34 years) with active proliferative retinopathy and 6 matched non-diabetic normal subjects were studied in random order with at least 2 weeks between treatments. Suppression of GHRH-induced GH release was demonstrated in both groups of subjects. Twenty-four hour GH secretion was not, however, suppressed in either the patient group (mean area under the GH curve mU·1−1·h−1 ± sd; baseline: 251 ± 108.7; after atropine: 174 ± 106.9; after propanthelene: 180 ± 72.4; P > 0.05) or in the control group (baseline: 103 ± 53.1; after atropine: 73 ± 83.6; after propanthelene: 122 ± 71.6; P >0.05). GH release at times of hypoglycemia was not suppressed. Mean IGF-I concentration was not significantly reduced. Two subjects (one patient and one control) could not tolerate atropine for more than one week. We conclude that repeated doses of atropine and propanthelene do not achieve complete 24-h GH suppression and are associated with a high incidence of unpleasant adverse reactions.
Localization of mRNA for the β-subunit of placental hCG by in situ hybridization
Authors: Wide Mariann , Persson Håkan , Lundkvist Örjan , Wide Leif
Published: December 2008

Abstract. The cellular origin of placental hCG is not yet completely established. Depending on the method used, the syncytium, cytotrophoblast or both types of tissue have been claimed to synthesize hCG. In the present study in situ hybridization was used on sections of chorionic villi in order to detect expression of the gene for the β-subunit of hCG (β-hCG). Placental tissue was obtained from the 8th to the 11th weeks of pregnancy, when the concentration of hCG is high. A cDNA clone, encoding the entire amino acid sequence of β-hCG, was used as a probe. Hybrids of β-hCG cDNA/mRNA were found only over the syncytiotrophoblast. Background noise was extremely low and no signals above that were detected in the cytotrophoblast cells. It is concluded that at this stage of pregnancy the gene for β-hCG is activated in the syncytial parts of chorionic villi and not in the cytotrophoblast.
Multiple pituitary hormone gradients from inferior petrosal sinus sampling in Cushing's disease
Authors: Crock Patricia A. , Pestell Richard G. , Calenti Anthony J. , Gilford Eric J. , Henderson J. Keith , Best James D. , Alford Frank P.
Published: December 2008

Abstract. Pre-operative bilateral simultaneous inferior petrosal sinus sampling with assessment of ACTH levels in the left and right sinuses and the periphery was performed in 9 patients with pituitary dependent Cushing's disease who were subsequently found at surgery to have basophil microadenomata. The novel observation of this study was the pattern of secretion of other pituitary hormones so that significant inter-sinus gradients ≥ 1.4:1 were seen for β-endorphin (2.8 ± 1.3, mean ± sem), PRL (4.2 ± 1.3) and GH (6.9 ± 2.4) as well as for ACTH (5.1 ± 1.1). There was no inter-sinus gradient for LH, FSH and TSH. In these 9 patients with adenomata, the correlations between the inter-sinus gradients for ACTH and β-endorphin were r = 0.95 (P <0.01), ACTH and PRL r = 0.90 (P < 0.01) and for ACTH and GH r = 0.89 (P <0.05). This close association between the gradients for ACTH and other anterior pituitary hormones could be due either to cosecretion of β-endorphin, PRL and GH by the ACTH-producing pituitary adenomata or to a paracrine effect of β-endorphin from the tumours on adjacent pituitary tissue. By reflecting the central pituitary hormone milieu, petrosal sinus sampling can give information about pituitary function unobtainable from peripheral hormone levels.
Biological effects and ultrastructural alterations of cis-tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in the uterus and vagina of newborn guinea pigs
Authors: Lecerf F. , Nguyen B.-L. , Pasqualini J. R.
Published: December 2008

Abstract. The biological and morphological effects of cis-tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen, administered sc alone (100 μg/animal) or combined with estradiol (20 μg/animal) were studied in the uterus and vagina of the guinea pig. After 2 days treatment the values of the uterine wet weights (mg ± sd of 6–10 animals in each study) were as follows: non-treated animals (control): 142 ± 15; animals treated with cis-tamoxifen: 119 ± 4; N-desmethyltamoxifen: 280 ± 20; 4-hydroxytamoxifen: 268 ± 25. The values after long treatment were: 177 ± 30; 490 ± 65; 394 ± 36 and 581 ± 60, respectively. After short treatment the weights of the vaginas were: control: 99 ± 20; cis-Tamoxifen: 67 ± 2; N-desmethyltamoxifen: 153 ± 25; 4-hydroxytamoxifen: 166 ± 7; and after the long treatment: 155 ± 40; 660 ± 41; 467 ± 38 and 502 ±61, respectively. N-desmethyltamoxifen and 4-hydroxytamoxifen increased the progesterone receptors in the uterus after short treatment (P < 0.01) but not after 12 days treatment. On the other hand, there was no effect on progesterone receptor in the vagina after the short treatment but a very stimulatory effect after the long treatment. The morphological alterations after 12-days treatment indicate that the three tamoxifen derivatives in the two tissues studied provoke intense alterations in different organelles. In conclusion, it is suggested that the tamoxifen derivatives can act as real agonists in the uterus and vagina of the newborn guinea pig, and they do not block the effect provoked by estradiol.
Specific radioimmunoassay for ovine bone gla-protein (osteocalcin)
Authors: Pastoureau P. , Merle B. , Delmas P. D.
Published: December 2008

Abstract. We developed a sensitive and specific radioimmunoassay for ovine bone gla-protein (osteocalcin) using a polyclonal rabbit antibody raised against ovine bone gla-protein. Bone from lambs was extracted in 0.5 mol/l EDTA and desalted on Sephadex G-25. Bone gla-protein was purified by gel filtration chromatography over Sephadex G-100 and ion-exchange chromatography on DEAE-Sephadex A-25. The protein, subjected to monodimensional electrophoresis migrated as a single spot in SDS PAGE with the same apparent molecular weight of 12 kD as bovine bone gla-protein. The amino acid composition of purified bone gla-protein was in agreement with a previous publication. The competitive RIA uses 125I-labelled bone gla-protein as a tracer and a complex of a second antibody and polyethylene glycol to separate free and antibody-bound 125I-labelled bone gla-protein. The intra- and inter-assay variations are less than 6 and 10%, respectively. There is no reactivity of our antisera with dog sera. The cross-reactivity is only partial with calf and human sera and complete with ovine sera. We measured bone gla-protein levels in serum of 96 normal male sheep of different ages. Serum bone gla-protein rapidly and significantly (P <0.001) decreased from 535 ± 169 μg/l at birth, to 240 ± 43 μg/l at 45 days, 152 ± 44 μg/l at 90 days, and 5.9 ± 0.7 μg/l at 7 years of age. In addition, bone gla-protein levels at birth were higher in normal birth weight than in hypotrophic lambs with low birth weight (535 ± 169 vs 271 ± 156 μg/l, P< 0.001). Furthermore, lambs raised outside in free conditions tended to have higher serum bone gla-protein levels than lambs raised under shelter (194 ± 53 vs 137 ± 34 μg/l), suggesting a role of breeding factors such as diet or relative immobilization on bone gla-protein levels. These results emphasize the interest of a RIA for the bone-specific protein bone gla-protein as a potential tool for experimental studies on skeletal growth and bone remodelling in a large animal.
Activated interstitial and intraepithelial thyroid lymphocytes in autoimmune thyroid disease
Authors: Cohen Shara B. , Weetman Anthony P.
Published: December 2008

Abstract. This study has further characterised the thyroid lymphocytic infiltrate in Graves' disease and Hashimoto's thyroiditis. Two population of lymphocytes were identified. The interstitial population occurred as a diffuse and a focal infiltrate; most cells were CD3-positive (T cells) and in 4 of 6 glands CD8 (suppressor-cytotoxic)-positive T cells predominated. The intraepithelial population was CD3-negative, CD8-positive. Both populations also contained a few NK (Leu 11b positive cells) in some glands. Many of the lymphocytes in both populations stained with UCHL1 and RFT2 suggesting that these are primed and activated cells, borne out by staining for transferrin receptor expression. Although thyroid follicular cells were Ia-positive, macrophages and dentritic cells were found in all cases, so that a role for antigen-presentation by all three potential candidates in autoimmune thyroiditis is possible.
Radioactive iodine thyroid uptake in patients with amiodarone-iodine-induced thyroid dysfunction
Authors: Martino E. , Bartalena L. , Mariotti S. , Aghini-Lombardi F. , Ceccarelli C. , Lippi F. , Piga M. , Loviselli A. , Braverman L. , Safran M. , Pinchera A.
Published: December 2008

Abstract. Amiodarone, an iodine-rich drug, represents at the present, at least in Europe, one of the most common sources of iodine-induced thyroid dysfunction. The drug may induce both hypothyroidism and thyrotoxicosis. In spite of the large iodine intake occurring during amiodarone therapy, 131I thyroid uptake is detectable in patients with amiodarone-iodine-induced hypothyroidism, irrespective of the presence or absence of underlying thyroid disease. In contrast, in patients with amiodarone-iodine-induced thyrotoxicosis, 131I thyroid uptake is normal or even elevated in those with co-existent underlying thyroid disorders, whereas it is very low in those with an apparently normal thyroid gland. Perchlorate discharge test was performed in 8 patients with hypothyroidism and in 5 patients with hyperthyroidism induced by amiodarone: a positive test was found in all hypothyroid patients and a negative test in all hyperthyroid patients.
Assessment of insulin action in man: role of hyperglycemia
Authors: Martens E. , Zick R. , Mitzkat H. J. , von zur Mühlen A. , Müller M. J.
Published: December 2008

Abstract. The effect of hyperglycemia on insulin-induced glucose metabolism (M) was investigated in healthy subjects using sequential clamp protocols at constant insulin + somatostatin infusions and varying plasma glucose. During euglycemia (4.8 mmol/l) M increased from 5.6 to 12.5 mg·kg−1·min−1 with increasing plasma insulin (0.34-3.00 nmol/l). At increasing glucose (6.7 mmol/l), M further increased (9.7 to 19.2 mg·kg−1·min−1) with the plasma insulin level (0.41 to 2.99 nmol/l). At a plasma glucose level of 9.8 mmol/l insulin (0.42 to 3.17 nmol/l) was still effective to increase M (13.7 to 25.2 mg·kg−1·min−1). Regression analysis showed that hyperglycemia does not only increase the maximal insulin-stimulated M, but also decreases the insulin concentration causing a half maximum effect. During prolonged clamp studies M increased by about 10% per h, independent by the plasma glucose level. We conclude that hyperglycemia increases M by increasing insulin responsiveness as well as insulin sensitivity. Data derived from euglycemic clamp studies alone are of limited value with respect to the assessment of insulin action.
Effects of IGF-I on the synthesis and processing of glycosaminoglycan in cultured chick chondrocytes
Authors: Kemp Stephen F. , Kearns Gregory L. , Smith W. Grady , Elders M. Joycelyn
Published: December 2008

Abstract. We have studied the effect of the somatomedin IGF-I on stimulation of synthesis of DNA, RNA, protein, and glycosaminoglycan in chick chondrocytes. Stimulation of RNA and protein synthesis was rapid, occurring within 10 min after addition of IGF-I. Stimulation of sulphation required a lag time of about 2 h, whether chains were initiated on native protein core or on the artificial acceptor 4-methyl-umbelliferyl-β-D-xyloside. DNA synthesis was not stimulated until after 10 h of exposure to IGF-I. Investigation of the rate of processing of proteoglycan core protein after pulselabelling chondrocytes with 35SO4 yielded data which were best described by a biexponential function. IGF-I had no effect on the t½ of the initial phase (16.44 min in the absence of IGF-I and 20.38 min in the presence of IGF-I). However, addition of IGF-I resulted in a decrease in the t½ of the terminal phase from 122.58 to 55.44 min, which may reflect an increase in synthesis in the enzymes necessary for polymerization and sulphation of proteoglycan.
Sources of calcium mobilized by glucagon in isolated rat hepatocytes
Authors: Mine Tetsuya , Kojima Itaru , Ogata Etsuro
Published: December 2008

Abstract. Effects of glucagon on cytoplasmic concentration of free calcium, [Ca2+]c, were studied in aequorin-loaded hepatocytes. Addition of 5 nmol/l glucagon resulted in a prompt, but transient increase in aequorin bioluminescence. Glucagon, at 5 nmol/l, induced an increase in [Ca2+]c even in medium containing 1 μmol/l calcium, although the response was considerably smaller than that observed in medium containing 1.0 mmol/l calcium. When hepatocytes incubated in the presence of 1 μmol/l extracellular calcium were first stimulated by phenylephrine and subsequently by either glucagon or angiotensin 11, there was a response of [Ca2+]c to glucagon, but not to angiotensin II. Dantrolene (50 μmol/l), which inhibits an increase in [Ca2+]c induced by phenylephrine, did not inhibit the increase in [Ca2+]c induced by glucagon. In contrast, dinitrophenol (50 μmol/l) abolished [Ca2+]c response to glucagon without abolishing the increase in [Ca2+]c induced by angiotensin II. These results suggest that glucagon mobilizes calcium from both intracellular and extracellular pools and that the intracellular calcium pool involved in glucagon action may be different from that mobilized by either phenylephrine or angiotensin II.
Effect of histamine on the secretion of pro-opiomelanocortin derived peptides in rats
Authors: Knigge Ulrich , Bach Flemming W. , Matzen Steen , Bang Peter , Warberg Jørgen
Published: December 2008

Abstract. In conscious male rats intracerebroventricular infusion of histamine increased the plasma concentrations of ACTH and β-endorphin immunoreactivity 2.5-fold (P < 0.01). Gel filtration of plasma revealed two peaks of β-endorphin immunoreactivity corresponding to β-endorphin and β-lipotropin. The two fractions increased almost equally in histamine-stimulated animals, whereas most of the circulating β-endorphin immunoreactivity in control animals corresponded to β-endorphin. Central infusion of the H1-receptor agonist 2-thiazolylethylamine and of the H2-receptor agonists dimaprit or 4-methylhistamine increased the plasma ACTH and β-endorphin immunoreactivity concentrations 2- and 3-fold, respectively (P < 0.01). Infused intracerebroventricularly, the H2-receptor antagonists cimetidine or ranitidine prevented the histamine-induced increase in plasma ACTH and β-endorphin immunoreactivity (P < 0.01), whereas the H1-receptor antagonist mepyramine inhibited the peptide responses by 70% (P < 0.01). Infused intra-arterially cimetidine or ranitidine inhibited the histamine-induced increase in plasma ACTH by 80% (P < 0.01) and plasma β-endorphin immunoreactivity by 45% (P < 0.05), whereas mepyramine or the other H1-receptor antagonist SKF-93944 inhibited the ACTH response by 50% (P < 0.05), but had no effect on the β-endorphin immunoreactivity. The results indicate that histamine increases the release of the pro-opiomelanocortin derived peptides ACTH, β-lipotropin and β-endorphin from the anterior pituitary lobe, whereas an effect of histamine on the release of β-endorphin from the neurointermediate lobe is possible. The effect of histamine seems primarily mediated by H2-receptors, whereas H 1-receptors appear to play a minor role.
Interleukin-1 induced impairment in pancreatic islet oxidative metabolism of glucose is potentiated by tumor necrosis factor
Authors: Eizirik Décio L.
Published: December 2008

Abstract. Recent observations suggest that human interleukin-1 (IL-1) causes functional impairment and death of pancreatic B-cells. This action seems to be potentiated by another cytokine, tumor necrosis factor (TNF). In the present investigation, the effects of recombinant human (r) IL-1 (10,30 and 150 pmol/l), and a combination of rIL-1 and human rTNF (25 μg/l), on islet glucose metabolism were examined in the presence of D-[5-3H] and D-[6-14C) glucose. The utilization of glucose was not affected by rIL-1 or rIL-1 plus rTNF. However, rIL-1 induced a 40% decrease in glucose oxidation, which was further potentiated by the addition of rTNF. rTNF alone did not impair islet glucose utilization or oxidation. It is concluded that rIL-1 induces a perturbation of islet glucose handling, mainly at the mitochondrial level. This impairment in the oxidative metabolism of glucose is further increased by the addition of rTNF.
A comparison of IGF-I levels measured by two commercially available radioimmunoassays
Authors: Silbergeld A. , Jaber L. , Lilos P. , Laron Z.
Published: December 2008

Abstract. Insulin-like growth factor I levels were measured in a parallel fashion in 77 extracted sera using the INCSTAR RIA (radioimmunoassay) and in the EDTA plasma of the same subjects by the NICHOLS RIA. The subjects suffered from untreated hGH deficiency, short stature, delayed and precocious puberty and acromegaly. Significant differences (P < 0.05) were found between the mean IGF-I levels of all groups using both RIA systems. However, using the INCSTAR RIA, 85% of IGF-I values in untreated hGH deficiency were below normal, and a rise in IGF-I detected in the sera of all 5 patients who were treated with hGH. Using NICHOLS RIA, 55% of basal IGF-I values were below normal and a hGH-stimulated rise in IGF-I was found in only two of the treated patients. The INCSTAR RIA seems more precise and reproducible than the NICHOLS RIA and enables better discrimination of hGH-deficient patients from age-matched controls.
Effect of melittin on pituitary-adrenal responsiveness to stress
Authors: Dunn Jon D. , Killion Jerald J.
Published: December 2008

Abstract. We previously have shown that melittin evokes a sustained increase in plasma corticosterone levels of the female rat. Significant increases occurred only during the morning and the duration of the response was increased from 48 h to 8 days by a second milittin injection 3 days after initial exposure to melittin. To further evaluate the effect of melittin on adrenocortical function, rats were given melittin at 09.00 h on days 1 and 4 and on day 8 rats were subjected to a variety of different stresses. Saline-injected rats served as controls. Blood for determining non-stress and stress levels of corticosterone concentration (RIA) was collected by decapitation. In all cases morning but not afternoon non-stress plasma corticosterone levels of melittin-injected rats were higher than those of saline-injected controls; afternoon non-stress corticosterone levels did not differ between groups. Melittin- and saline-treated rats showed comparable corticosterone responses to a morning 2-min restraint stress. In contrast, melittin treatment facilitated the pituitary-adrenal response to rotational and surgical stress as well as the stress of removing one rat from a cage of two. Fifteen min after removal of the first rat of a cage of two, plasma corticosterone levels of the melittin-injected rat were significantly higher than those of saline-injected rats. Likewise, plasma corticosterone levels of melittin-treated rats were higher (P < 0.05) than those of saline-injected rats 15 min after rotational (10 rpm) and surgical (jugular cutdown and blood withdrawal) stress. Collectively these data indicate that exposure to melittin (and/or the resulting increase in morning corticosterone levels) may have a significant influence on the pituitary-adrenal responsiveness to stress.
Quantitative in-situ hybridization histochemistry of anterior pituitary hormone mRNA species in human pituitary adenomas
Authors: Levy A. , Lightman S. L.
Published: December 2008

Abstract. We have examined the anterior pituitary hormone messenger (m) RNA species contained in biopsies of 41 pituitary tumours obtained at hypophysectomy using in-situ hybridization histochemistry. The adenoma were grouped clinically into 12 prolactinomas, 8 somatotrope adenomas, 16 non-functioning, 4 Nelson's syndrome, and 1 thyrotrope adenoma. Of these, 10 contained no detectable anterior pituitary hormone mRNA species and 11 appeared to be expressing the gene responsible for the patients' clinical state in isolation. In a number of cases the accumulation of specific mRNA species was not accompanied by an increase in the circulating levels of the corresponding hormone or subunit. Evidence of activation of more than 1 anterior pituitary hormone gene was present in 16 adenomas of which only 7 showed a pattern of activation or amplification of gene expression which would suggest deregulation of either the inositol phospholipid or cAMP second messenger pathway. It was therefore not possible from these data to postulate that isolated deregulation of a single second messenger transduction pathway is a common etiological factor in pituitary tumour formation.
Oxytocin reduces exercise-induced ACTH and cortisol rise in man
Authors: Coiro V. , Passeri M. , Davoli C. , Bacchi-Modena A. , Bianconi L. , Volpi R. , Chiodera P.
Published: December 2008

Abstract. The effect of oxytocin on the ACTH, cortisol, GH and PRL response to physical exercise was investigated in 6 normal men. In addition, the possible involvement of endogenous opioids in the mediation of oxytocin action was evaluated. After fasting overnight, each subject was tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 20 min in all subjects. Tests were carried out under administration of oxytocin (2000 mIU as an iv bolus injection plus 32 mIU/min per 30 min) or naloxone (10 mg as an iv bolus injection) alone; furthermore, the effect of oxytocin together with naloxone (10 mg as an iv bolus injection) was evaluated. In the remaining test, normal saline was given instead of drugs. Plasma ACTH, cortisol, PRL and GH concentrations were significantly increased by physical exercise. Administration of oxytocin, naloxone or their combination was without effect on the PRL and GH rise elicited by exercise. In contrast, the exercise-induced ACTH and cortisol response was significantly raised by naloxone and reduced by oxytocin. When oxytocin was preceded by administration of naloxone, the ACTH and cortisol response to exercise was not reduced by oxytocin. These data show that oxytocin is capable of inhibiting the rise in ACTH and cortisol, but not in GH and PRL induced by physical exercise. Since naloxone abolished the inhibitory effect of oxytocin, oxytocin action on ACTH and cortisol secretion might be supposed to be mediated by an opioid pathway. However, we cannot exclude that oxytocin and naloxone act at different sites in the hypothalamic-pituitary system.
Mechanism of action of the factor(s) secreted by rat seminiferous tubules and inhibiting interstitial cell testosterone production in vitro
Authors: Syed V. , Khan S. A. , Lindh M. , Ritzén E. M.
Published: December 2008

Abstract. Rat seminiferous tubules secrete a factor which inhibits LH-dependent steroidogenesis by interstitial cells. The inhibitory activity was found to be specific for the testes, as cytosols from other rat tissues such as the kidney, heart, spleen, liver and epididymis had no significant effect on testosterone production by interstitial cells. Preliminary characterization by Ultrogel AcA 44 gel chromatography demonstrated that the active substance in SMST has a molecular weight between 40–50 kD. Spent medium from incubation of seminiferous tubules (SMST) caused a dose-dependent inhibition of LH-or cholera toxin-stimulated in vitro testosterone production by rat interstitial cells. However, SMST failed to inhibit forskolin-stimulated steroidogenesis. The effect of SMST was not altered by pre-incubating the cells with the sulfhydryl reagent, N-ethylmaleimide. Considering the proposed mode of action of these modulators of adenylate cyclase activity, the present studies suggest that a high molecular weight testis specific factor acts through the guanine nucleotide-binding stimulatory regulatory protein of the adenylate cyclase complex to inhibit LH-dependent testosterone production by Leydig cells.
Pharmacological doses of calcitonin reduce sex hormone levels in rat plasma
Authors: Mahrous Talaat S. , Nakhla Atif M.
Published: December 2008

Abstract. Administration of a pharmacological dose of salmon calcitonin into rats (10 MRC U/kg body weight) significantly reduced plasma concentrations of testosterone and estradiol in a time-dependent fashion. This apparently was mediated by a diminished secretion of luteinizing hormone and follicle-stimulating hormone, the levels of which were also significantly reduced after 1 h of calcitonin administration.
A rapid and simple assay for growth hormone-binding protein activity in human plasma
Authors: Baumann Gerhard , Shaw Melissa A. , Amburn Klaus
Published: December 2008

Abstract. The newly discovered circulating growth hormone binding proteins dictate a re-evalutation of the state of GH in plasma in health and disease as the binding proteins are known to affect GH metabolism and action. We describe a rapid and simple GH-binding assay that allows determination of free and complexed plasma GH, as well as GH-binding protein activity as an index of GH-binding protein levels, with relative ease. The method is based on incubation of plasma with 125I-GH and separation of bound from free GH on small DEAEcellulose columns; it can be used on a large scale for routine determinations. The results obtained by this method are comparable to those obtained with the previously used slow and more cumbersome gel filtration technique. Initial data obtained in normal subjects and certain disease states show that the bound fraction of plasma GH is similar in men, women and children, is unaffected by pregnancy or acute infection, but is marginally decreased in liver cirrhosis. In acromegaly, binding protein activity also appears normal when allowance is made for partial saturation of the binding proteins by the high prevailing GH levels. The technique we describe should facilitate investigations of normal and abnormal regulation of the GH binding proteins.
Long-term effects of thyrotropin-releasing hormone and histidyl-proline diketopiperazine on the maturation of homeothermia and mitochondrial enzyme activities in neonatal rats
Authors: Miyamori Chiaki , Kato Taizo , Imura Eiichi , Murata Akisato , Sato Tamotsu , Sakura Naoki , Hashimoto Tadashi
Published: December 2008

Abstract. To elucidate the mechanism by which TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro)), act on the maturation of homoiothermy, the chronic effects of intrathecal administration of the peptides on body temperature, serum thyroid hormone levels, and mitochondrial energy-producing enzyme activities were examined in neonatal rats. The two peptides or an equimolar mixture of both were injected intrathecally at a dose of 3, 6 and 9 nmol for 7 consecutive days during the 1st, 2nd or 3rd week of life, respectively. Control rats were treated with saline and they were sacrificed at 6 weeks of age. Although food and water intake were not decreased, body weight gain was slightly reduced in the rats treated with TRH or cyclo(His-Pro) during the 1st and 2nd week of life, whereas the mixturetreated rats showed normal weight gain. Body temperature at 25°C was not different in the TRH- and cyclo(HisPro)-treated groups, whereas after cold exposure (5°C for 3 h), the groups treated with TRH during the 1st and 2nd week of life had an impaired thermoregulation at 5 weeks of age. Serum T4 and T3 concentrations were similar in all groups, except in the rats treated with TRH during the 2nd week of life; their thyroid hormone levels were slightly reduced. The TRH treatment suppressed mitochondrial cytochrome c reductase and glucose-6-phosphatase activities, whereas cyclo(His-Pro) reduced cytochrome c reductase and malic enzyme activities. In contrast, α-glycerophosphate dehydrogenase was enhanced by both treatments. These results suggest that TRH and cyclo(His-Pro) modulate the central thermoregulatory mechanism and produce particular changes in the mitochondrial respiratory chains in peripheral thermogenic tissues.
Naloxone affects the release of cortisol, but not of vasopressin or oxytocin, in dehydrated sheep
Authors: Thornton S. N. , Parrott R. F.
Published: December 2008

Abstract. Ovariectomized ewes (N = 7) were dehydrated for 24 h and then given iv injections of saline vehicle or 8 or 64 mg naloxone hydrochloride in saline. Blood samples were taken by jugular venepuncture before and after dehydration and at intervals during the 90 min period directly following naloxone treatment. Plasma concentrations of AVP, OT and cortisol were measured by radioimmunoassay. Plasma AVP levels and osmolality increased with dehydration, OT concentrations showed no consistent change, and cortisol levels were unaffected. After administration of naloxone, AVP and OT concentrations did not alter. The sampling procedure increased plasma cortisol levels and the duration of this response was prolonged by the 64 mg dose of naloxone.
'Salivary peptide P-C' of human pancreatic B-cells shares only partly immunoreactivity with salivary peptide P-C indicating a new B-cell protein which is different from insulin
Authors: Ito Seiki , Suzuki Toshimitsu , Isemura Satoko , Sanada Kazuo , Anaguchi Hiroyuki , Shimizu Hirohiko , Maruyama Toshihiro , Shibata Akira
Published: December 2008

Abstract. Salivary peptide P-C like immunoreactivity, originally isolated from human whole saliva has later been found in the human pancreatic B-cells. In the present work an indirect immunofluorescence technique using monoclonal antibodies against isolated salivary peptide P-C was applied to Bouin fixed pancreas and parotid glands to study the possible identity of the two substances. Positive P-C immunofluroescence was found in the serous cells of parotid glands but not in pancreatic B-cells, suggesting that pancreatic P-C substance is not salivary peptide P-C itself, but a substance sharing the common antigenic site with salivary peptide P-C. To examine this, an indirect immunofluorescence technique using polyclonal P-C antisera pre-absorbed with six kinds of synthetic fragments (1–22, 23–44, 23–29, 30–44, 30–38 and 38–44) of salivary peptide P-C was applied to the human pancreas. The result showed that pancreatic P-C substance was a substance which shares the common antigenic site with the 38–44 amino acid residue of salivary peptide P-C. Western blot analysis using extracts of human pancreata further showed that pancreatic P-C substance is not a precursor of insulin but a protein with molecular weight of 11 500 dalton, indicating the presence of a new protein in the insulin secretory granules of human pancreatic B-cells.
Effects of aging on human plasma renin: simultaneous multiple assays of enzyme activity and immunoactivity of plasma renin
Authors: Higaki Jitsuo , Morishita Ryuichi , Ogihara Toshio , Nishiura Masaru
Published: December 2008

Abstract. The effects of aging on plasma renin in normotensive volunteers were evaluated by conventional indirect RIA of angiotensin I and a newly developed direct RIA. Plasma renin activity and the plasma concentration of active renin measured by radiometric assay with monoclonal antibody were significantly lower in 14 subjects over 60 years than in 15 subjects under 60 years (plasma renin activity: 0.5 ± 0.1 vs 1.7 ± 0.4 nmol · 1−1 · h−1, P< 0.01; plasma active renin: 0.50 ± 0.05 vs 0.87 ± 0.13 pmol/l, P< 0.01, means ± sem), wheres neither the total renin activity nor the total plasma renin concentration measured by the newly developed immunometric assay were different in the two groups. In another study, the plasma renin concentration, total renin concentration and immunoreactive total renin concentration measured by direct RIA with polyclonal antibody were determined in 17 young (<60 years) and 12 elderly (≧60 years) subjects. Plasma renin concentration was significantly lower in the elderly subjects (1.7 ± 0.2 nmol · 1−1 · h−1) than in young subjects (3.4 ± 0.7 nmol · 1−1 · h−1, P< 0.05), but the total renin concentration and immunoreactive total renin concentrations in the two groups were not significantly different. These results indicate that the total renin content of the plasma does not change, whereas the active renin content decreases with age in normal subjects, and suggest that activation of prorenin to active renin may be impaired in elderly subjects.
TRH pharmacokinetics and nerve stimulation evoked prostatic fluid secretion during TRH infusion in the dog
Authors: Liberman Claudio , Nogimori Tsuyoshi , Wu Chih Fang , Van Buren Teresa , Wilson John , Miller Tracy , Smith Emil , Emerson Charles H.
Published: December 2008

Abstract. The pharmacokinetics of TRH have been determined in man and the rat as well as other species whose serum contains TRH degrading enzymes, TRH pharmacokinetics have not been determined in the dog. This species is unusual in that its serum contains little or no TRH degrading activity. TRH pharmacokinetics were determined from measurements of plasma TRH concentrations during and following a 1-h infusion of TRH, 20 μg · kg−1 · min−1, into dogs bearing prostatic urethral cannula. During TRH administration prostatic fluid secretion was evoked by hypogastric nerve stimulation and the content of TRH immunoreactive material in prostatic fluid was determined. Prostatic fluid was also collected after hypogastric nerve stimulation in dogs that did not receive TRH infusion. The TRH plasma profile in TRH-infused dogs exhibited two-compartment characteristics with an initial half-time of 10.4 ± 5.4 (mean ± sd) min, a terminal half-time of 69.4 ± 24 min, and a metabolic clearance rate of 7.64 ± 4.48 ml · min−1 · kg−1. These findings suggest that the half-time of TRH is longer, and its metabolic clearance rate is less, in the dog than in humans or rats. TRH administration was not associated with altered nerve induced prostatic fluid secretion. Prostatic fluid samples contained TRH immunoreactive material regardless of whether they were collected after epithelial cell stimulation with pilocarpine, or after hypogastric nerve stimulation. In contrast to previous results with vasoactive intestinal peptide, TRH does not acutely alter prostatic fluid secretion. As has been reported for prostatic tissue extracts, immunoreactive material is present in prostatic fluid and appears to arise from epithelial cells.
Thyrotropin-releasing hormone in geriatric patients: intravenous versus intranasal application
Authors: Szabolcs István , Ploenes Christoph , Bernard Wolfdieter , Herrmann Jorg
Published: December 2008

Abstract. The effect of intravenous versus intranasal TRH stimulation was compared in geriatric patients. In patients receiving both iv and nasal tests (N = 35) there was a good correlation between the TSH responses, but in 3 cases the suspicion of inadequate nasal TRH effect arose. The coefficient of correlation of basal to ΔTSH was better in iv tested patients (116 patients in each group, one half having a positive the other half a negative TRH test). In the majority of patients with suspicious incongruity of basal and Δ TSH the nasal test was done. The specificity and sensitivity of various basal TSH 'cut-off' points to predict a positive TRH test were better in patients with iv TRH tests (in each group 96 consecutively admitted patients). Insufficiency of the nasal test in geriatric patients is mainly explained by the inability of the old people to aspirate the nasal spray effectively. Besides the advantages of iv TRH application in geriatric patients, the frequency of adverse reactions (14% versus 0%) must be considered. Thus, in a hospitalized geriatric patient, the TRH test should be performed iv in the recumbent position; however, for examination of geriatric outpatients the nasal test is recommended.