bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women
Authors: Lado-Abeal Joaquin , Liz Jose L , Rey Carlos , Febrero Manuel , Cabezas-Cerrato Jose 
Published: December 2008

Lado-Abeal J, Liz JL, Rey C, Febrero M, Cabezas-Cerrato J. Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women. Eur J Endocrinol 1996;135:293–8. ISSN 0804–4643
It is well established that valproate increases hypothalamic concentrations of γ-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile luteinizing hormone (LH) secretion in humans, our group recently found that administration of valproate had no significant effect on pulsatile LH secretion in late follicular and mid-late luteal phase normal women. However, the results of several studies of rats suggest that GABAergic regulation of LH secretion may depend on steroid levels. The objective of this work was to determine whether regular administration of sodium valproate inhibits pulsatile LH secretion in ovariectomized women. Twelve women who had undergone ovariectomy for causes other than malignant tumors were each studied in two 8 h sessions, in each of which blood samples were taken every 5 min. The first session was the control; for the second, 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluorescence spectrophotometry, and LH, estradiol and progesterone by radioimmunoassay. The serum LH series were subjected to a deconvolution procedure to reconstruct the pattern of pituitary LH secretion. Luteinizing hormone pulses were identified by the authors' nonparametric method. Control and post-valproate results were compared with regard to number of pulses, pulse duration, the quantity of LH secreted in each pulse, interpulse interval and mean serum LH level. There was no statistically significant difference between control and post-valproate results for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovariectomized women. This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator.
J Cabezas-Cerrato, Endocrinology and Nutrition Service, General Hospital of Galicia, c/Galeras s/n 15705, Santiago de Compostela, La Coruña, Spain
17β-Estradiolid Ca influx rapid Ca2+ prostate cancer cells
Authors: Audy MC , Vacher P , Dufy B 
Published: December 2008

Audy MC, Vacher P, Dufy B, 17β-Estradiol stimulates a rapid Ca2+ influx in LNCaP human prostate cancer cells. Eur J Endocrinol 1996;135:367–73. ISSN 0804–4643
Prostate growth is known to be controlled by steroids such as androgens and estradiol. For this reason steroids (estradiol, adrenal androgens) or steroid inhibitors are commonly used as palliative treatments for prostate carcinoma. In view of the pivotal role played by Ca2+ ions in cell proliferation, we decided to investigate the effects of 17β-estradiol (E2) on intracellular calcium concentration ([Ca2+]i) in a human prostate tumor cell line, LNCaP. In this study, we show that E2 induced a dose-dependent (0.1–100 nmol/l) influx of Ca2+ in these cells. These effects occurred rapidly after the beginning of the ejection and were maintained in the presence of the hormone (plateau phase). Estradiol-induced Ca2+ influx was unaffected by the saturation of the androgen receptor with pure antiandrogen flutamide. The use of tamoxifen, an antiestrogen binding to nuclear receptors, or E2 covalently linked to bovine serum albumin that cannot penetrate the cell membrane, did not block the ([Ca2+]i) response. Our results suggest the existence of E2 binding sites at the plasma membrane surface of LNCaP cells, linked to calcium signalling and, more specifically, Ca2+ channels.
MC Audy, Laboratoire de Neurophysiologie, URA 1200, 146 rue Léo Saignat, Université de Bordeaux II, 33076 Bordeaux Cedex, France
Cyclic AMP regulates expression of activin and inhibin subunit mRNAs in the mouse placenta and decidua: a short communication
Authors: Yamaguchi Masaaki , Fujii Mitsuhisa , Miyake Akira 
Published: December 2008

Yamaguchi M, Fujii M, Miyake A. Cyclic AMP regulator expression of activin and inhibin subunit mRNAs in the mouse placenta and decidua. Eur J Endocrinol 1996;135:379–81. ISSN 0804–4643
We examined whether cAMP regulates expression of activin/inhibin subunit mRNAs in the mouse placenta and decidua. 8-Bromo-cAMP inhibited expression of inhibin α-subunit mRNA but stimulated expression of activin/inhibin βA- and βB-subunit mRNAs in placenta and decidua by the 3rd day of culture. Forskolin and cholera toxin also regulated expression of activin/inhibin subunit mRNAs in the same manner. However, activin-A did not affect expression of activin/inhibin subunit mRNAs. These findings suggest that cAMP inhibits inhibin production but stimulates activin production in the mouse placenta and decidua.
Masaaki Yamaguchi, Department of Obstetrics and Gynecology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565, Japan
Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)—evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins
Authors: Vaag Allan A , Holst Jens J , Vølund Aage , Beck-Nielsen Henning 
Published: December 2008

Vaag AA, Holst JJ, Volund A, Beck-Nielsen H. Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)—evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins. Eur J Endocrinol 1996;135:425–32. ISSN 0804–4643
The incremental glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses (areas under curves; AUCs) were determined during a standard 180-min 75-g oral glucose tolerance test in a group of 12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) and 13 matched controls without family history of diabetes using highly sensitive and specific radioimmunoassay hormone assays. Data were analysed using multifactor analysis of variance (ANOVA) to identify and correct for possible covariates and to correct for multiple comparisons. Fasting plasma GLP-1 and GIP concentrations were similar in all groups. The twins with frank NIDDM had a decreased incremental GLP-1 response during oral glucose ingestion compared with controls without family history of diabetes (AUC±sem; 0.55 ± 0.14 vs 1.17 ± 0.25 (mmol/l) × min, p < 0.05). The incremental GLP-1 secretion in the non-diabetic twins was not significantly different from neither their NIDDM co-twins nor the controls without family history of diabetes. The incremental GIP responses were similar in all study groups. Gender was identified as the major independent covariate for incremental glucose, insulin, GIP and GLP-1 responses, with higher values of all parameters in females. Waist-to-hip ratio and body mass index (BMI) were identified as independent but oppositely directed covariates for the incremental GLP-1 responses (waist-to-hip ratio: r = 0.43, p < 0.02; BMI: r= −0.34, p = 0.06). Incremental GLP-1 responses correlated with incremental insulin responses in the combined study population (N = 37; R = 0.42, p = 0.01). In conclusion, a decreased intestinal GLP-1 secretion may contribute to the abnormal insulin secretion during oral glucose ingestion in NIDDM twins. However, decreased secretion of gut incretin hormones (GLP-1 or GIP) does not explain all of the defects of pancreatic insulin secretion in NIDDM patients/twins or in non-diabetic individuals (identical twins) with a genetic predisposition to NIDDM.
Allan Vaag, Odense University Hospital, Department of Endocrinology and Internal Medicine M, Sdr. Boulevard, Odense, DK-5000, Denmark
Spontaneous remission of ectopic Cushing's syndrome due to pheochromocytoma: a case report
Authors: Loh Keh-Chuan , Gupta Rekha , Shlossberg Allan H 
Published: December 2008

Loh K-C, Gupta R, Shlossberg AH. Spontaneous remission of ectopic Cushing's syndrome due to pheochromocytoma: a case report. Eur J Endocrinol 1996;135:440–3. ISSN 0804–4643
A young female adult with Cushing's syndrome arising from ectopic production of corticotropin (ACTH) from an adrenal pheochromocytoma showed spontaneous clinical and biochemical remission of hypercortisolism after a brief period of ketoconazole administration. Despite continued remission of the hypercortisolism over the next 18 months, there was progressive catecholamine hypersecretion with significant morbidity as a result of the pheochromocytoma. Surgical resection of the left adrenal gland revealed a pheochromocytoma showing focal cytoplasmic immunostaining for ACTH and marked diffuse compact cell hyperplasia in the adrenocortical tissue. To our knowledge this is the first reported case of spontaneous clinical and biochemical remission of ectopic ACTH production from a pheochromocytoma. The pathogenesis of the remission remains unknown.
Keh-Chuan Loh, Division of Endocrinology and Metabolism, Dalhousie University, 5303 Morris Street, Halifax, Nova Scotia B3J 1B6, Canada
Effects of N-methyl-d-aspartate and kainic acid on prolactin secretion in prepubertal female rats
Authors: Pinilla Leonor , González Dolores , Tena-Sempere Manuel , Aguilar Rafaela , Aguilar Enrique 
Published: December 2008

Pinilla L, González D, Tena-Sempere M, Aguilar R, Aguilar E. Effects of N-methyl-d-aspartate and kainic acid on prolactin secretion in prepubertal female rats. Eur J Endocrinol 1996;135:464–8. ISSN 0804–4643
The control of prolactin (PRL) secretion by N-methyl-d-aspartate (NMDA) and kainic acid (KA), agonists of NMDA and kainate receptors, and the interactions between NMDA and KA with nitric oxide (NO) were analysed in prepubertal female rats. For this purpose, serum PRL concentrations and hypothalamic and pituitary dopamine (DA) and serotonin (5-HT) concentrations were measured in females injected with NMDA, KA or two blockers of NO synthase: Nw-nitro-l-arginine methyl ester (NAME) and Nw-nitro-l-arginine (NA). Also, the effects of combined administration of NMDA and KA with the blockers of NO synthase were analyzed. We found that PRL release was inhibited 15 min after NMDA and KA administration, an effect probably mediated through the release of hypothalamic DA, as shown by the higher pituitary DA concentrations after NMDA or KA administration. The inhibitory effect of NMDA was preceded by an increase in serum PRL levels, observed at 5 and 10 min after NMDA administration. Nw-Nitro-l-arginine methyl ester alone inhibited prolactin secretion, and both NAME and NA abolished the inhibitory effect of KA, but not that of NMDA. We conclude that administration of NMDA exerted a dual action on PRL secretion: initially DA release was inhibited, leading to an increase in PRL secretion that in turn stimulated DA release and decreased serum PRL concentrations. Kainic acid also inhibited PRL secretion by releasing DA, an effect blocked by NO synthase inhibitors.
Enrique Aguilar, Department of Physiology, Faculty of Medicine, University of Córdoba, E-14004, Spain
Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat
Authors: Torsello Antonio , Grilli Roberta , Luoni Marina , Guidi Margherita , Ghigo Maria Cristina , Wehrenberg William B , Deghenghi Romano , Müller Eugenio E , Locatelli Vittorio 
Published: December 2008

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643
We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH.
Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy
Lung volumes and respiratory muscle strength in adult patients with childhood- or adult-onset growth hormone deficiency: effect of 12 months' growth hormone replacement therapy
Authors: Merola Bartolomeo , Longobardi Salvatore , Sofia Matteo , Pivonello Rosario , Micco Assunta , Di Rella Francesca , Esposito Vincenzo , Colao Annamaria , Lombardi Gaetano 
Published: December 2008

Merola B, Longobardi S, Sofia M, Pivonello R, Micco A, Di Rella F, Esposito V, Colao A, Lombardi G. Lung volumes and respiratory muscle strength in adult patients with childhood- or adult-onset growth hormone deficiency. Effect of 12 months' growth hormone replacement therapy. Eur J Endocrinol 1996;135:553–8. ISSN 0804–4643
We have described impairment of the respiratory function in adult patients with childhood-onset growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient before and after 6 and 12 months of recombinant GH treatment. Ten adults diagnosed as GH deficient in childhood, ten adults diagnosed as GH deficient in adulthood and ten healthy subjects entered the study. For each subject, evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, record of flow–volume curves, measurement of static lung volumes and lung diffusing capacity. Childhood-onset GH-deficient patients had a significant reduction of maximal inspiratory (p < 0.01) and maximal expiratory (p < 0.05) mouth pressures. Total lung capacity, vital capacity and functional residual capacity were significantly reduced compared to healthy subjects (p < 0.05). Conversely, residual volume and diffusing lung capacity did not show any significant change. No significant change of the ratio between the percentage forced expiratory volume in 1 s and the forced vital capacity was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. Adult-onset GH-deficient patients had only a significant reduction of maximal expiratory pressure compared to healthy subjects (p < 0.05). After 6 months of treatment no significant differences in any of the evaluated parameters were found. After 12 months of treatment patients with childhood-onset GH deficiency show a significant improvement of lung volumes (p < 0.01) and maximal respiratory mouth pressures (p < 0.005), whereas adult-onset GH-deficient patients show a significant improvement of maximal expiratory pressure (p < 0.05). In conclusion, the results of this study showed that adult patients affected with childhood-onset GH deficiency suffer from an impairment of the ventilatory function due to a reduction of lung volumes and a decrease of respiratory pressures probably due to a reduction of respiratory muscle strength. This impairment was reversed after 12 months of treatment with recombinant GH. Conversely, adult-onset GH-deficient patients had only an impairment of the maximal expiratory pressure, probably due to respiratory muscle weakness re-established after 12 months of GH therapy.
Gaetano Lombardi, Via G. Santacroce 40/a, 80129 Naples, Italy
Increased cardiovascular response to caffeine in perimenopausal women before and during estrogen therapy
Authors: Del Rio G , Menozzi R , Zizzo G , Avogaro A , Marrama P , Velardo A 
Published: December 2008

Del Rio G, Menozzi R, Zizzo G, Avogaro A, Marrama P, Velardo A. Increased cardiovascular response to caffeine in perimenopausal women before and during estrogen therapy. Eur J Endocrinol 1996; 135:598–603. ISSN 0804–4643
Perimenopause and menopause may be associated with an increased risk of cardiovascular disease, so we have investigated the cardiovascular and catecholamine response to caffeine in perimenopausal women compared to young cycling premenopausal subjects. Caffeine (250 mg per os) was administered to nine perimenopausal women and nine premenopausal women. The perimenopausal women repeated the test after 4 months of percutaneous estrogen replacement therapy. Systolic and diastolic blood pressure, pulse rate, plasma norepinephrine, epinephrine, glucose, insulin and free fatty acids were determined at 0, 15, 30, 45, 60, 90 and 120 min after caffeine administration. No differences were found in the basal values of systolic blood pressure, diastolic blood pressure, pulse rate, norepinephrine, epinephrine, insulin, glucose and free fatty acids between perimenopausal women, both before and after therapy, and premenopausal women. Caffeine induced a higher increase of systolic (F = 4.9; p < 0.05) and diastolic blood pressure (F = 4.7; p < 0.05) in perimenopausal women before and during estrogen therapy as compared with premenopausal women. Pulse rate increased significantly only in perimenopausal women before therapy (F = 6.5; p < 0.03). These data show that perimenopause either before or during short-term estrogen therapy is associated with enhanced cardiovascular reactivity to caffeine. This phenomenon is not due to increased adrenergic and metabolic responses.
Graziano Del Rio, Department of Internal Medicine via del Pozzo, 71 41100 Modena, Italy
Islet cell-specific autoantibodies in children with insulin-dependent diabetes mellitus and their siblings at clinical manifestation of the disease
Authors: Vähäsalo Paula , Knip Mikael , Karjalainen Jukka , Tuomilehto-Wolf Eva , Lounamaa Raisa , Åkerblom Hans K , _ _ 
Published: December 2008

Vähäsalo P, Knip M, Karjalainen J, Tuomilehto-Wolf E, Lounamaa R, Åkerblom HK, and the Childhood Diabetes in Finland Study Group. Islet cell-specific autoantibodies in children with insulin-dependent diabetes mellitus and their siblings at clinical manifestation of the disease. Eur J Endocrinol 1996;135:689–95. ISSN 0804–4643
The aim of this work was to characterize both newly diagnosed insulin-dependent diabetic subjects and their siblings with positive tests for islet cell-specific autoantibodies (ICSAA) and to evaluate whether there is an association between the ICSAA levels detected in the diabetic children and siblings. We analysed 781 probands younger than 15 years of age for islet cell antibodies (ICA) and 755 for insulin autoantibodies (IAA) and 610 of their 3–19-year-old non-diabetic siblings for ICA and IAA upon diagnosis of the proband. Islet cell antibodies were observed in 657 of the probands (84.1%) and IAA in 353 (46.8%). The ICA-positive probands were younger in age and had higher IAA levels than the ICA-negative probands, while the IAA-positive probands were younger and had higher levels of ICA than the IAA-negative probands. Islet cell antibodies were detected in 46 (7.5%) and IAA in 16 (2.6%) siblings, and the ICA-positive siblings had higher IAA levels than the ICA-negative siblings. A falling trend was seen in the frequency of ICA [2A7E] 20 Juvenile Diabetes Foundation units in the siblings with decreasing degrees of HLA identity with the index case. Infections during the preceding year, especially respiratory infections, increased the prevalence of both ICA and IAA in the diabetic children at diagnosis and the frequency of IAA in the siblings. There was a significant, although weak, correlation between the IAA levels of the probands and those of their siblings when 594 pairs were tested (rs = 0.15; p < 0.001). No association could be seen between the ICA levels of the probands and those of their siblings, not even when including only HLA-identical proband–sib pairs in the analysis. The lack of any relation between ICA levels in the probands and siblings supports the view that there may be multiple exogenous factors capable of inducing ICA formation or else a common factor but variable responsiveness in the index case and the sibling.
Paula Vähäsalo, Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland
Growth hormone increases serum 1,25-dihydroxyvitamin D levels and decreases 24,25-dihydroxyvitamin D levels in children with growth hormone deficiency
Authors: Wei Shi , Tanaka Hiroyuki , Kubo Toshihide , Ono Taeko , Kanzaki Susumu , Seino Yoshiki 
Published: December 2008

Abstract
The influence of growth hormone (GH) on calcium–phosphorus metabolism and modulation of vitamin D metabolism has been demonstrated, but the mechanism remains unclear. We investigated the effect of a 6-month course of GH therapy on vitamin D and mineral metabolism in twelve GH-deficient children. Before GH therapy, levels of vitamin D metabolites and other biochemistry data were within normal ranges. All patients responded to GH therapy with increased growth velocity. 1,25-Dihydroxyvitamin D levels increased after 1 month of treatment and remained at these higher levels, with a significant increase found at 3 months (P < 0·05), whereas 24,25-dihydroxyvitamin D levels were decreased at 1 and 3 months, the latter being a significant decrease (P < 0·05), and then returned to the baseline levels at 6 months. 25-Hydroxyvitamin D levels did not change significantly. A significant increase in serum insulin-like growth factor-I (IGF-I) levels occurred during the 6 months of treatment (1 month, P < 0·01; 3 and 6 months, P < 0·001). Serum parathyroid hormone (PTH) levels decreased significantly at 3 and 6 months (3 months, P < 0·01; 6 months, P < 0·05). Serum calcium and phosphorus levels did not change significantly. Significant increases were found in the urinary calcium/urinary creatinine ratio (3 and 6 months, P < 0·05) and the percent tubular reabsorption of phosphorus levels (1 and 3 months, P 0·05). The results of this study confirmed the actions of GH on renal tubules with increases in calcium excretion and phosphorus reabsorption, and indicate that the action of GH on modulating vitamin D metabolism may be IGF-I mediated, not PTH mediated.
European Journal of Endocrinology 136 45–51