bluuebunny/crossref_metadata_2025 huggingface dataset:
Earliest prevention of endemic goiter by iodine supplementation during pregnancy
Authors: Liesenkötter Klaus Peter , Göpel Wolfgang , Bogner Ulrich , Stach Barbara , Grüters Annette
Published: December 2008

Liesenkötter KP, Göpel W, Bogner U, Stach B, Grüters A. Earliest prevention of endemic goiter by iodine supplementation during pregnancy. Eur J Endocrinol 1996;134:443–8. ISSN 0804–4643

During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. It has been demonstrated that with decreasing iodine supply maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. Therefore iodine supplementation during pregnancy is now strongly recommended also in areas of moderate iodine deficiency. To monitor the success of iodine supplementation and its theoretical risk of increasing the frequency of thyroid autoantibodies, we have investigated the thyroid volume, thyroid function, urinary iodine excretion and antibodies to thyroid peroxidase at 10–12 weeks of gestation and postpartum in 38 mothers receiving 300 μg potassium iodide/day and in 70 mothers without iodine supplementation. In all of their newborns thyroid volume was determined by ultrasound. The thyrotropin (TSH) levels and antibodies to thyroid peroxidase (TPO-ab) in the neonates were measured in dried blood spots on filter paper from their newborn screening. Urinary iodine excretion was increased significantly after iodine supplementation in mothers (p < 0.001) and their newborns (<0.05). No hypo- or hyperthyroidism was observed in the mothers or newborns. Interestingly, no difference of maternal thyroid volumes was observed between the two groups after pregnancy, but the volumes of the thyroid glands in newborns of mothers who received iodine were significantly (p < 0.004) lower (0.7 ± 0.4 ml) than in the control group (1.5 ± 1.1 ml). There was no change in the frequency of TPO-ab in either group after pregnancy. In four mothers transplacental passage of these antibodies was documented by positive measurement in the blood sample of the newborn. This study documents that iodine supplementation during pregnancy in an area of moderate iodine deficiency results in a lower size of neonatal thyroid volume and that this supplementation was not accompanied by an increase in the frequency of TPO-ab.

Klaus Peter Liesenkötter, Kinderklinik Kaiserin Auguste Victoria Haus (KAVH), Virchow-Klinikum der Medizinische Fakultät der Humboldt-Universität zu Berlin, Heubnerweg 6, 14059 Berlin, Germany
Bovine granulosa cell culture for assessment of potency and specificity of antibodies to pregnant mares' serum gonadotrophin
Authors: Kuran Mehmet , Broadbent Peter J , Hutchinson JS Morley
Published: December 2008

Kuran M, Broadbent PJ, Hutchinson JSM. Bovine granulosa cell culture for assessment of potency and specificity of antibodies to pregnant mares' serum gonadotrophin. Eur J Endocrinol 1996;134:497–500. ISSN 0804–4643

Antibodies to pregnant mares' serum gonadotrophin (PMSG) neutralize the effect of PMSG in vivo and increase the number of transferable embryos when administered at the optimum time relative to the preovulatory luteinizing hormone (LH) surge in PMSG-stimulated cows. The objective of the present study was to investigate the possible use of bovine granulosa cells in a serum-free culture system as a bioassay for antibodies to PMSG. Granulosa cells (2–3 × 105 viable cells) were cultured with varying doses of PMSG and/or an anti-PMSG for 4 days. Whilst progesterone production (ng/μg DNA) of granulosa cells was stimulated by PMSG (p < 0.01) in a dose-dependent manner, increasing amounts of anti-PMSG neutralized (p < 0.01) this stimulatory effect of either follicle-stimulating hormone or LH on progesterone production of bovine granulosa cells in vitro. The bovine granulosa cell culture system is a potential in vitro bioassay method for testing the specificity and the neutralizing capacity of different anti-PMSG preparations.

Mehmet Kuran, Ondokuz Mayis Universitesi, Ziraat Fakultesi, Zootekni Bolumu, 55149 Samsun, Turkey
Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans: comparison with growth hormone
Authors: Hussain Mehboob A , Schmitz Ole , Jorgensen Jens OL , Christiansen Jens S , Weeke Jorgen , Schmid Christoph , Froesch E Rudolf
Published: December 2008

Hussain MA, Schmitz O, Jorgensen JOL, Christiansen JS, Weeke J, Schmid C, Froesch ER. Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans. Eur J Endocrinol 1996;134:563–7. ISSN 0804–4643

Insulin-like growth factor I (IGF-I) is considered to mediate some of the growth-promoting and metabolic effects of growth hormone (GH). Growth hormone treatment of healthy and GH-deficient subjects is accompanied by increased conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues. Whether these effects are mediated by IGF-I is unknown. To assess the respective roles of these hormones on thyroid hormone metabolism we have treated two groups of subjects. The first group consisted of eight healthy subjects who were treated with IGF-I 10 μg·kg−1·h−1 sc for 5 days). The second group consisted of eight subjects with combined GH and thyrotropin (TSH) deficiency due to acquired pituitary disease. They were treated with IGF-I (10 μg·kg−1·h−1 sc for 7 days), GH (2 IU m−2 sc q.i.d.) or both hormones together. The IGF-I treatment in healthy subjects led to an increase in free T3 (FT3) and a reduction in TSH levels, whereas FT4 and total T4 (TT4) levels remained unchanged. In the second group—in which all subjects were substituted with oral lthyroxine—treatment with IGF-I led to an elevation of FT3 in the face of unchanged T4 levels. Growth hormone alone and GH plus IGF-I resulted in a more pronounced elevation in T3 level. The results suggest that IGF-I partially mediates the well-known effects of GH on peripheral conversion of T4 to T3. However, GH has more pronounced effects on thyroid hormones that apparently are not mediated by IGF-I.

ER Froesch, Division of Endocrinology and Metabolism, Department of Internal Medicine, University Hospital of Zürich, Rámistr, 100, 8091 Zürich, Switzerland
Solubilization, reconstitution and molecular properties of the triiodothyronine transport protein from rat erythrocyte membranes
Authors: Samson Michel , Osty Jeannine , Thibout Hélène , Blondeau Jean-Paul
Published: December 2008

Samson M, Osty J, Thibout H, Blondeau J-P. Solubilization, reconstitution and molecular properties of the triiodothyronine transport protein from rat erythrocyte membranes. Eur J Endocrinol 1996;134: 660–8. ISSN 0804–4643

Triiodothyronine (T3) transport through the mammalian erythrocyte membrane is mediated by a transport system related to the aromatic amino acid transport system T. The T3-binding component of this transport system could be photolabeled with [125I]T3 as a 52-kD protein, and subsequently solubilized with non-ionic detergents. Upon purification by ion-exchange chromatography, the photolabeled 52-kD protein solubilized with octylglucoside (OG) resolved into several peaks, suggesting charge heterogeneity of labeled proteins. The saturable [125I]T3 binding to rat erythrocyte membranes was completely inhibited by non-ionic detergents at concentrations about 20 times lower than those that solubilized membrane. Therefore, detergent-free proteoliposomes were generated from the detergent-soluble extracts by treatment with a polystyrene adsorbent. Proteoliposomes prepared from OG-soluble extract contained the highest specific activity of T3 binding. The Kd of the T3 binding sites (4.5 nmol/l) and the competitive inhibition constant of tryptophan (120 μmol/l) were similar to those for native membranes. The photolabeling of the 52-kD protein in these proteoliposomes was prevented by tryptophan and T4, but not by leucine or the d-isomer of T3, corresponding to the transport specificity of system T. The 52-kD protein solubilized with OG from native membranes was partially purified by ion-exchange chromatography. The 52-kD protein was detected by photoaffinity labeling in the purified fraction only after addition of erythrocyte membrane phospholipids to generate proteoliposomes. This indicates that the association of 52-kD protein with phospholipids is critical for T3 binding.

JP Blondeau, U96 INSERM, 80 Rue de Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France
High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency
Authors: Roelen Corné A , Koppeschaar Hans P , de Vries Wouter R , Zelissen Pierre M , Snel Yvonne E , Doerga Manorath E , Thijssen Jos H , Blankenstein Rien A
Published: December 2008

Roelen CA, Koppeschaar HP, de Vries WR, Zelissen PM, Snel YE, Doerga ME, Thijssen JH, Blankenstein RA. High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency. Eur J Endocrinol 1996;135:82–6. ISSN 0804–4643

The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements.

HPF Koppeschaar, Department of Endocrinology, University Hospital Utrecht, HPL00.407, PO Box 85500, 3508 GA Utrecht, The Netherlands
Depression of dehydroepiandrosterone in Japanese diabetic men—comparison between non-insulin-dependent diabetes mellitus and impaired glucose tolerance
Authors: Yamauchi Akira , Takei Izumi , Kasuga Akira , Kitamura Yuko , Ohashi Norimi , Nakano Satomi , Takayama Sumiyo , Nakamoto Shinya , Katsukawa Fuminori , Saruta Takao
Published: December 2008

Yamauchi A, Takei I, Kasuga A, Kitamura Y, Ohashi N, Nakano S, Takayama S, Nakamoto S, Katsukawa F, Saruta T. Depression of dehydroepiandrosterone in Japanese diabetic men—comparison between non-insulin-dependent diabetes mellitus and impaired glucose tolerance. Eur J Endocrinol 1996;135:101–4. ISSN 0804–4643

Hyperglycemia is known to reduce dehydroepiandrosterone (DHEA) circulating levels; however, the mechanism by which hyperglycemia decreases DHEA is not elucidated. In this study, serum DHEA and DHEA sulfate (DHEA-S) levels were compared in 50 men with non-insulin-dependent diabetes mellitus (NIDDM) and 50 age-matched men with impaired glucose tolerance (IGT) receiving only diet therapy. Serum concentrations of DHEA and DHEA-S in the NIDDM group were significantly lower than in the IGT group (7.8 and 9.7 nmol/l vs 3.4 and 4.9 μ mol/l, respectively; p< 0.01) but there was no significant difference in immunoreactive insulin between the two groups. When the results from both groups were combined, HbA1c was significantly inversely related to DHEA (r = −0.243. p<0.01) and DHEA-S (r = −0.305, p<0.01). Immunoreactive insulin showed no correlation with DHEA and DHEA-S. Multiple regression analysis showed that HbA1c was independently negatively related to both DHEA and DHEA-S. We conclude that hyperglycemia may decrease serum DHEA and DHEA-S in Japanese men with NIDDM, but the depression of DHEA(-S) is independent of serum insulin level.

Akira Yamauchi, Department of Internal Medicine, Keio University School of Medicine. 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan
Excretion of 2- and 3-monomethyl ethers of 2-hydroxyestrogens in healthy male volunteers
Authors: Banger Markus , Hiemke Christoph , Haupt Margitta , Knuppen Rudolf
Published: December 2008

Banger M, Hiemke C, Haupt M, Knuppen R. Excretion of 2- and 3-monomethyl ethers of 2-hydroxyestrogens in healthy male volunteers. Eur J Endocrinol 1996;135:193–7. ISSN 0804–4643

The formation of catecholestrogens by 2-and 4-hydroxylation of monophenolic estrogens represents a major route of estrogen metabolism. In vitro and in vivo studies on catecholestrogens have shown that 2-hydroxylated catecholestrogens are primarily inactivated by O-methylation, while O-methylation of 4-hydroxylated estrogen is of minor importance. In the present study the in vivo production of isomeric 2- and 3-monomethyl ethers of 2-hydroxyestrogens was measured in 12 healthy omnivorous male volunteers aged 51 ± 4 years. The sum of estrone and 17β-estradiol, 2-hydroxyestrogens (sum of 2-hydroxyestrone and 2-hydroxyestradiol), 4-hydroxyestrogens (sum of 4-hydroxyestrone and 4-hydroxyestradiol) and the sum of the isomeric monomethyl ethers of 2-hydroxyestrone and 2-hydroxyestradiol were measured in 24-h urinary samples. The determinations included hydrolysis of steroid conjugates, separation by chromatographic steps and final quantification by radioimmunoassay. The specificity of the antibodies enabled differentiation between the isomeric monomethyl ethers. The mean urinary excretion rates were 8.8 ± 2.9 μg/24 h for estrone plus estradiol, 5.2 ± 2.4 μg/24 h for the 2-hydroxyestrogens and 1.3 ± 0.5 μg/24 h for the 4-hydroxyestrogens. The 2- and 3-monomethyl ethers of the 2-hydroxyestrogens were found in all individuals, with excretion rates of 5.8 ± 2.6 μg/24 h for 2-methoxyestrogens and 3.6 ± 1.1 μg/24 h for 2-hydroxyestrogen-3-methyl ethers. The findings indicated that 2-hydroxyestradiol is metabolized in vivo by 2-O-methylation and, to a lesser extent, by 3-O-methylation.

Markus Banger, Department of Psychiatry, University of Essen, Virchowstr. 174, 45147 Essen, Germany
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
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

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
Growth hormone binding protein and growth hormone availability in acromegalic patients treated with long-acting octreotide (Sandostatin-LAR)
Authors: Fisker Sanne , Kaal Andreas , Montini Marcella , Pedroncelli Alberto , Pagani Giorgio , Ørskov Hans
Published: December 2008

Objective: In the medical treatment of acromegaly different factors are influencial; among these the impact on growth hormone binding protein (GHBP) has not been clarified.

Design: Twenty acromegalic patients and nineteen age- and gender-matched normal subjects participated in this study. The patients were treated for 21 months with depot long-acting microsphere-enclosed octreotide (Sandostatin-LAR). Previously, all the patients were treated s.c. with octreotide t.i.d. After a 2-week wash-out period (baseline) the patients received the first i.m. injection of the long-acting octreotide. The first two injections were administered at 60-day intervals; thereafter the injections were at 28-day intervals.

Methods: The levels of GHBP, complexed GHBP, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were determined in fasting serum samples.

Results: In the 2-week wash-out period GHBP levels decreased from 1·13 ± 0·17 to 0·92 ± 0·15 nmol/l (P < 0·05). During the 21-months treatment, GHBP increased again to 1·10 ± 0·16 nmol/l. In the age- and gender-matched control group GHBP levels were significantly higher at all times (1·95 ± 0·21 nmol/l, P(all) < 0·02). Mean levels of 8-h GH decreased from 12·6 ± 2·58 μg/l at baseline to 1·97 ± 0·20 μg/l after 21 months of treatment (P < 0·05). Mean 8-h GH levels were unchanged during long-acting octreotide treatment compared with levels during s.c. treatment (1·97 ± 0·20 μg/l and 1·90 ± 0·20 μg/l respectively). In fasting blood samples GH-complexed GHBP ranged from 13·8 ± 2·4% (9 months) to 25·4 ± 4·5% (baseline) of total GHBP. Serum IGF-I increased from 367 ± 45 to 764 ± 80 μg/l (P < 0·05) during the 2-week wash-out period and decreased to 290 ± 35 μg/l (P < 0·05) after 21 months of treatment with long-acting octreotide. IGF-I levels after 21 months were significantly lower than during s.c. octreotide treatment (P < 0·05).

Conclusion: Serum GHBP levels are similar during treatment with long-acting octreotide as compared with regular octreotide. Furthermore, significant changes in GHBP can occur within 2 weeks. Finally, in addition to the lowering effect on GH levels, the induced increase in GHBP levels may imply a further advantage in octreotide treatment of acromegaly, circulating GH bound to GHBP may less readily reach the tissues.

European Journal of Endocrinology 136 61–66
Increased neutrophil insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced functional capacity in patients with untreated Laron syndrome
Authors: Bjerknes Robert , Vesterhus Per , Aarskog Dagfinn
Published: December 2008

Insulin-like growth factor-I (IGF-I) is a growth hormone-dependent peptide with growth and immunoregulatory properties, and in Laron syndrome growth hormone insensitivity induces impaired production of IGF-I. In the present study we have determined the neutrophil expression of IGF-I receptors (IGF-I-Rs), as well as the IGF-I-induced priming of neutrophil functional capacity, in two children with Laron syndrome treated with recombinant human IGF-I, and in age-matched controls. Before treatment, the patient neutrophil expression of IGF-I-Rs was significantly increased. However, with replacement therapy the neutrophil IGF-I-R expression was downregulated to levels similar to those of the controls within one month. In the patients, the phagocytic capacity and oxidative burst of unprimed neutrophils were normal and similar to controls before the start of treatment. Moreover, IGF-I efficiently primed both patient and control neutrophils to increase their phagocytic capacity and oxidative burst in vitro. However, before therapy, the priming response to IGF-I was significantly stronger in the neutrophils in the patients than in the controls. The present data support earlier studies by us and others demonstrating that IGF-I is a potent regulator of mature neutrophil function, but also suggest that these leukocytes may function normally in the presence of very low levels of IGF-I in vivo.

European Journal of Endocrinology 136 92–95
Late post-prandial hypoglycaemia as the sole presenting feature of secreting pancreatic β-cell adenoma in a subtotally gastrectomized patient
Authors: Del Sindaco Paola , Casucci Giovanni , Pampanelli Simone , Polonsky Kenneth , Fanelli Carmine , Torlone Elisabetta , Santeusanio Fausto , Brunetti Paolo , Bolli Geremia B
Published: December 2008

In this paper we describe for the first time late post-prandial hypoglycaemia as the sole presenting feature of an insulinoma in a patient who had previously undergone subtotal gastrectomy. The symptoms of hypoglycaemia always occurred 1–3 h after meals, not in the fasting state. Because of the history of gastrectomy and because post-prandial hypoglycaemia was reproduced by an oral glucose tolerance test, the diagnosis of reactive hypoglycaemia was made. Eighteen months later a fasting test was performed: venous plasma glucose decreased from 3·8 mmol/l to 2·7 mmol/l between 14 and 20 h of fast while plasma immunoreactive insulin did not decrease and plateaued at 185 pmol/l. Plasma C-peptide (0·9 nmol/l) and proinsulin (70 pmol/l, split 64, 65) were also elevated. All islet hormones increased in response to i.v. glucose and were suppressed after diazoxide. Although pre-operative procedures were negative in localizing an insulinoma, the patient underwent an operation and an insulinoma was detected at the body level of the pancreas. Thus, insulinoma should be considered in the differential diagnosis of reactive hypoglycaemia in gastrectomized patients. Response of islet hormones to glucose and their suppression by diazoxide are evidence of a secreting insulinoma even in the absence of preoperative localization of the pancreatic adenoma.

European Journal of Endocrinology 136 96–99
Lack of suppressive action of luteal factors from sheep corpus luteum on LH response to exogenous LHRH in ovariectomized, pregnant and post-partum ewes
Authors: Al-Gubory Kaïs Hussain
Published: December 2008

In vivo studies have provided evidence of a non-steroidal factor from ovine corpora lutea (CL) of pregnancy called LH-release inhibiting factor (LH-RIF), which specifically inhibits tonic LH release without affecting FSH secretion. To study the possible pituitary site of action of LH-RIF and other factors from sheep CL of pregnancy, the LH response to LHRH was investigated in ovariectomized (OVX) ewes pretreated with ovine luteal extract (oLE) from CL of mid-pregnancy, and in pregnant and post-partum ewes from which the CL were removed at mid-pregnancy. In view of the fact that human follicular fluid (hFF) contains a non-steroidal factor, called gonadotrophin surge-attenuating factor, which attenuates the LHRH-induced LH release, it was clearly important to examine the LHRHinduced LH release in OVX ewes pretreated with oLE or hFF. In experiment 1, the LH and FSH responses (the maximum LH and FSH concentrations, the time to maximum LH and FSH concentrations and the area under the LH and FSH response curves) to a single i.v. injection of 5 μg of the LHRH agonist buserelin was not significantly different between ewes pretreated with oLE and ewes pretreated with BSA. Although the LHRH-induced LH and FSH release was slightly attenuated in OVX ewes pretreated with hFF as compared with OVX ewes pretreated with BSA, the maximum LH and FSH concentrations and the area under the LH and FSH response curves were not significantly different between the two groups of ewes. In experiment 2, the LH responses to a single i.v. injection of 0.5 μg LHRH on days 80 and 100 of pregnancy were not significantly different between intact ewes and ewes from which the CL were removed on day 70 of pregnancy. In both groups of ewes the maximum LH concentration and the area under the LH response curve were significantly lower (p<0·02) on day 100 than on day 80 of pregnancy. In experiment 3, the LH responses to a single i.v. injection of 50 μg LHRH on day 140 of pregnancy and on day 10 post-partum were not significantly different between intact ewes and ewes from which the CL were removed on day 70 of pregnancy. In both groups of ewes the maximum LH concentration and the area under the LH response curve were significantly lower (p<0·01) on day 140 of pregnancy than on day 10 post-partum.

These experiments provide evidence for a lack of suppressive action of luteal secretory products from the ovine CL of pregnancy on the pituitary LH response to LHRH in OVX, pregnant and post-partum ewes.

European Journal of Endocrinology 136 114–120
Percutaneous ethanol injection therapy in the treatment of thyroid and parathyroid diseases
Authors: Bennedbæk Finn Noe , Karstrup Steen , Hegedüs Laszlo
Published: December 2008

Relevant English language articles published from 1966 to 1995 regarding ethanol therapy in the treatment of thyroid and parathyroid diseases were identified through a MEDLINE search and manual searches of identified articles.

The sclerosing properties of ethanol have been recognized for many years and have offered interventional possibilities in the management of various benign as well as malignant lesions. The mechanism of action of ethanol appears to be related to a direct coagulative necrosis and local partial or complete small vessel thrombosis. Ultrasound-guided percutaneous ethanol injection therapy (PEIT) is rapid and performed on an out-patient basis and has now gained wide acceptance due to the accumulating evidence of the efficacy and safety of this therapeutic tool. Yet, there is a lack of prospective, randomized clinical trials comparing PEIT with 131I therapy or surgery with regard to its effects, especially long-term ones and it should therefore still be considered an experimental procedure.

In benign endocrine diseases, PEIT has shown promising results in the treatment of autonomous thyroid nodules, benign solitary cold solid as well as cystic thyroid nodules and parathyroid tumours. Its use in pretoxic and toxic thyroid nodules has been evaluated in several uncontrolled studies, all demonstrating a high success rate in spite of the large number of treatments needed. So far efficacy and cost-effectiveness seem inferior to 131I and surgery. Short-term results of PEIT in benign cystic thyroid nodules are convincing with a high cure rate, but no controlled studies with long-term results are available. Preliminary results suggest that PEIT could become an alternative to surgical excision or levothyroxine therapy in the symptomatic solid cold benign thyroid nodule.

Ultrasound-guided PEIT of parathyroid tumours has proven to be a useful method in highly selected patients in whom surgery has been found non-attractive and medical treatment ineffective. However, no prospective randomized trials have been published comparing the results of PEIT in parathyroid tumours with conventional surgical and medical treatments.

PEIT has never been tested against standard therapy, but seems inferior to 131I and surgery. Side-effects caused by ethanol injection are generally few and transient and are related to the injection into solid nodules rather than cysts. Ethanol injection into solid profund nodules may seriously jeopardize subsequent surgery because of perinodular fibrosis. As an experimental procedure, not yet evaluated sufficiently, it should be reserved for patients who cannot or will not undergo standard therapy. Caution in routine use is advisable.

European Journal of Endocrinology 136 240–250
Apoptosis and p53 suppressor gene protein expression in human anterior pituitary adenomas
Authors: Green Victoria L , White Michael C , Hipkin Leslie J , Jeffreys Richard V , Foy Patrick M , Atkin Stephen L
Published: December 2008

Human anterior pituitary adenomas proliferate and express the p53 tumour suppressor gene protein, but it is not known if apoptosis (programmed cell death) occurs. Therefore, the detection of apoptosis was undertaken in tumorous human anterior pituitary tissue and compared with p53 protein expression, tumour type and tumour size. Apoptosis (detected by the in situ end labelling technique) and p53 suppressor gene protein (detected by DO. 1-antibody immunocytochemistry) were determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning adenomas). Two normal anterior pituitaries were also included in this study. Pre-operative tumour size was scored 1 to 4 from magnetic resonance imaging radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas and 33% of non-functioning adenomas, although this difference was not significant. The p53 tumour suppressor protein was found in 7 of 31 tumours (23%), 33% of somatotrophinomas and 19% of nonfunctioning adenomas. Apoptosis and p53 protein expression were not found in normal anterior pituitary. In conclusion, apoptosis occurs in human anterior pituitary adenomas, but no significant association was found between apoptosis and p53 protein expression, tumour type or tumour size.

European Journal of Endocrinology 136 382–387