bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of luteinized unruptured follicles in the rat after injection of luteinizing hormone early in pro-oestrus
Authors: Mattheij John AM , Swarts Hans JM
Published: December 2008

Mattheij JAM, Swarts HJM. Induction of luteinized unruptured follicles in the rat after injection of luteinizing hormone early in pro-oestrus. Eur J Endocrinol 1995;132:91–6. ISSN 0804–4643

The cause of formation of luteinized unruptured follicles (LUF) is unknown. Formation of LUF was studied after injection of a varying small dose of luteinizing hormone (LH) with or without subsequent injection of gonadotrophin-releasing hormone (GnRH); in addition, the effect of suppression of prolactin on LUF formation was studied. Luteinization without ovulation occurred in virtually all graafian follicles, if 0.5–1.0 μg of LH was injected some hours before the presumed endogenous LH surge (suppressed by Nembutal); with increasing doses of LH progressively increasing numbers of ovulations were observed. If in early pro-oestrus 1 μg of GnRH was given 4 h after 1 μg of LH, formation of LUF was partly prevented; if the interval between LH and GnRH was 8 h or more, the great majority of graafian follicles developed into LUF. If early in pro-oestrus 1 μg of LH was given and 8 h later 0.1 μg of a potent GnRH analogue, about 50% of the follicles became LUF; in similarly treated rats, suppression of prolactin by ergocryptine reduced but did not prevent LUF formation. The data support the idea that deficient LH secretion in the period before ovulation may be involved in the formation of LUF.

John AM Mattheij, Department of Human and Animal Physiology, Haarweg 10, 6709 PJ Wageningen, The Netherlands
Erythropoietin and testicular steroidogenesis: the role of second messengers
Authors: Foresta Carlo , Mioni Roberto , Bordon Paola , Gottardello Francesco , Nogara Andrea , Rossato Marco
Published: December 2008

Foresta C, Mioni R, Bordon P, Gottardello F, Nogara A, Rossato M. Erythropoietin and testicular steroidogenesis: the role of second messengers. Eur J Endocrinol 1995;132:103–8. ISSN 0804–4643

It has been demonstrated that erythropoietin (EPO) influences rat and human Leydig cell steroidogenesis, stimulating testosterone production through a direct and specific receptor-mediated mechanism. The aim of this study was to investigate the mechanism by which recombinant human erythropoietin (rHuEPO) exerts its stimulatory effect on rat Leydig cells. Recombinant human EPO did not induce, at any dose tested (10−10 to 10−13 mol/l), an increase in either cAMP or cGMP, suggesting that in Leydig cells the effect of rHuEPO does not involve the adenylate or guanylate–cyclase systems. The role of transmembrane calcium flux in rHuEPO-stimulated steroidogenesis was studied by evaluating the effect of calcium channel blocker, verapamil, and by the 45Ca2+ uptake method. Verapamil did not influence rHuEPO-induced testosterone secretion and rHuEPO did not modify calcium recycling, indicating that calcium transmembrane flux is not involved in the rHuEPO effect. The protein kinase C inhibitor staurosporine (10, 30, 100 and 300 nmol/l) inhibited rHuEPO-stimulated testicular steroidogenesis in a dose-dependent manner. This indirect evidence suggests that the stimulatory effect of rHuEPO on rat Leydig cells may involve protein kinase C activation.

Carlo Foresta, Institute of Internal Medicine, Via Ospedale Civile 105, 35128 Padova, Italy
Biosynthetic growth hormone increases the collagen deposition rate in rat aorta and heart
Authors: Brüel A , Oxlund H
Published: December 2008

Brüel A, Oxlund H. Biosynthetic growth hormone increases the collagen deposition rate in rat aorta and heart. Eur J Endocrinol 1995;132:195–9. ISSN 0804–4643

Disorders of the cardiovascular system often are associated with alterations in the metabolism of the collagens of these tissues. A method for in vivo determination of collagen deposition rate in small tissue samples is delineated and used for assessment of the effect of biosynthetic growth hormone (GH) injections on the collagen deposition rate in rat aorta and cardiac musculature. Rats were injected with GH, and the controls with saline, twice daily for 7 days. The in vivo collagen deposition rate was measured by injecting iv a large dose of [3H]-proline with a flooding dose of "cold" proline, followed by determination of the production of [3H]-hydroxyproline during a 4-h labelling period. Extractable collagens that were not bound in the tissue and therefore do not contribute mechanical strength to it were removed from the samples. 3H-Labelled- and "cold" amino acids were assessed by reversed-phase HPLC combined with simultaneous flow scintillation detection on the same sample. In the control group the deposition per hour was 0.13 ± 0.02% (mean ± sem) in aortic intima media and 0.72 ± 0.09% in cardiac left ventricular musculature. Growth hormone induced a threefold increase (p < 0.001 and p < 0.01, respectively) in the collagen deposition rate: 0.45 ± 0.06% in aortic intima media and 2.43 ± 0.45% in cardiac left ventricular musculature. The method described enables a rapid and sensitive determination of collagen deposition per hour in small tissue samples from experimental animals. The collagen deposition rate of cardiac musculature is fivefold higher compared with that of aortic intima media. Biosynthetic GH induces a threefold increase in the collagen deposition rate of these tissues.

Hans Oxlund, Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark
Epidermal growth factor stimulates the cell growth of the PA-1 teratocarcinoma cell line in an autocrine/paracrine fashion
Authors: Shigeta Hiroyuki , Taga Michiyoshi , Sakakibara Hideya , Minaguchi Hiroshi
Published: December 2008

Shigeta H, Taga M, Sakakibara H, Minaguchi H. Epidermal growth factor stimulates the cell growth of the PA-1 teratocarcinoma cell line in an autocrine/paracrine fashion. Eur J Endocrinol 1995;132: 200–5. ISSN 0804–4643

In order to investigate the biological significance of epidermal growth factor (EGF) in the cell function of teratocarcinoma cells, we examined the production, binding and cell proliferative effect of EGF in PA-1 human ovarian teratocarcinoma cell line. The immunoreactivity of EGF in PA-1 cell-conditioned medium was detected by human EGF radioimmunoassay, and prepro-EGF mRNA was demonstrated in PA-1 cells by Northern blot analysis. An [125I] EGF binding study showed the presence of EGF receptor with very high binding affinity and relatively low numbers of binding sites in PA-1 cells. Furthermore, the growth of PA-1 cells was stimulated by EGF and inhibited by anti-EGF monoclonal antibody. These results suggest strongly that EGF plays an important role in controlling the growth of teratocarcinoma cells as an autocrine/paracrine growth factor.

Michiyoshi Taga, Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, 3–9 Fukuura, Kanazawa-ku, Yokohama 236, Japan
Increase in human placental glucose transporter-1 during pregnancy
Authors: Sakata Masahiro , Kurachi Hirohisa , Imai Takashi , Tadokoro Chikae , Yamaguchi Masaaki , Yoshimoto Yasuhiro , Oka Yoshitomo , Miyake Akira
Published: December 2008

Sakata M, Kurachi H, Imai T, Tadokoro C, Yamaguchi M, Yoshimoto Y, Oka Y, Miyaka A. Increase in human placental glucose transporter-1 during pregnancy. Eur J Endocrinol 1995;132:206–12. ISSN 0804–4643

Glucose transporter-1 (GLUT1) has been found in high abundance in human placentas. The purpose of this study was to analyze the changes in the level of GLUT1 during pregnancy. We have analzyed the gestational changes in human placental GLUT1 by [3H]cytochalasin B binding assay, immunoblot analysis and Northern blot analysis. Levels of [3H]cytochalasin B binding to placental membrane in pregnancy at 7–10, 18–20 and 38–40 weeks were 4.2 ± 0.47, 5.2 ± 0.46 and 7.2 ± 0.40 (mean±sem, N = 4) μmol/kg protein, respectively. Amounts of 49-kD and 60-kD proteins detected in immunoblot analysis increased during pregnancy in parallel with [3H]cytochalasin B binding to placental membrane. The GLUT1 mRNA levels also increased during pregnancy. Immunohistochemical examination showed that GLUT1 was localized in the plasma membranes of trophoblast cells. These findings showed that the GLUT1 level increased during pregnancy in human placentas and suggest that GLUT1 may play an important role in fetal development.

Masahiro Sakata, Department of Obstetrics and Gynecology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan
Effects of transforming growth factor α (TGF-α) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells
Authors: Arai Mariko , Tsushima Toshio , Isozaki Osamu , Demura Hiroshi , Shizume Kazuo , Emoto Naoya , Miyakawa Megumi , Nozoe Yasuko , Murakami Hitomi , Ohmura Eiji
Published: December 2008

Arai M, Tsushima T, Isozaki 0, Demura H, Shizume K, Emoto N, Miyakawa M, Nozoe Y, Murakami H, Ohmura E. Effects of transforming growth factor α (TGF-α) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells. Eur J Endocrinol 1995;132:242–8. ISSN 0804–4643

Transforming growth factor α (TGF-α) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-α has similar effects using porcine thyroid cells in culture. Recombinant human TGF-α dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-α is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-α, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-α again was approximately 50% that of EGF. Transforming growth factor α did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-α. Thus, we conclude that TGF-α inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-α mRNA in porcine thyroid cells. These observations suggest that TGF-α acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells.

T Tsushima, Department of Medicine 2, Tokyo Women's Medical College, Kawadacho 8–1, Shinjukuku, Tokyo 162, Japan
Missense mutation in CYP11B1 (CGA[Arg-384] → GGA[Gly]) causes steroid 11β-hydroxylase deficiency
Authors: Nakagawa Yuichi , Yamada Masao , Ogawa Haruo , Igarashi Yoshio
Published: December 2008

Nakagawa Y, Yamada M, Ogawa H, Igarashi Y. Missense mutation in CYP11B1 (CGA[Arg-384] → GGA[Gly]) causes steroid 11β-hydroxylase deficiency. Eur J Endocrinol 1995;132:286–9. ISSN 0804–4643

Steroid 11β-hydroxylase deficiency (11β-OHD) is an autosomal recessive hereditary defect and one of the causes of congenital adrenal hyperplasia. The 11β-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Twelve types of mutations of this gene have been reported previously in patients with 11β-OHD, including one Japanese patient. We detected an additional previously uncharacterized mutation: R384G mutation, a single C→G base substitution in the codon 384 of the exon 7 changing an arginine (CGA) to a glycine (GGA) by sequencing the CYP1 1B1 gene of Japanese siblings with 11β-OHD. We analyzed also the CYP11B1 gene of their unaffected family members. Their grandfather was homozygous for the normal gene, whereas their grandmother, parents and younger brother were heterozygous for the mutation. These results indicate that the cause of 11β-OHD is heterogeneous even in the Japanese population, which is ethnically homogeneous.

Yuichi Nakagawa, Department of Pediatrics, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-31, Japan
Percutaneous computed tomography-guided ethanol injection in aldosterone-producing adrenocortical adenoma
Authors: Rossi Riccardo , Savastano Silvia , Tommaselli Antonio P , Valentino Rossella , Iaccarino Vittorio , Tauchmanova Libuse , Luciano Antonio , Gigante Marianna , Lombardi Gaetano
Published: December 2008

Rossi R, Savastano S, Tommaselli AP, Valentino R, Iaccarino V, Tauchmanova L, Luciano A, Gigante M, Lombardi G. Percutaneous computed tomography-guided ethanol injection in aldosteroneproducing adrenocortical adenoma. Eur J Endocrinol 1995;132:302–5. ISSN 0804–4643

The feasibility, safety and effectiveness of percutaneous computed tomography-guided ethanol injection (PEI-CT) was investigated in a patient affected by aldosterone-producing adenoma (APA). A 42-year-old male patient with typical features of hyperaldosteronism presented a solitary left adrenal adenoma measuring 2 cm, with a normal contralateral gland, evidenced by both CT scan and adrenal [75Se-19]-nor-cholesterol scintigraphy. After normalization of potassium plasma levels, 4 ml of sterile 95% ethanol with 0.5 ml of 80% iothalamate sodium was injected. The procedure was completed in about 30 min. No severe pain or local complication was noted. Five hours after PEI, a fourfold and a twofold increase in aldosterone and cortisol plasma levels were observed, respectively. After 11 days on a normal sodium and potassium diet, normal potassium plasma levels and reduced aldosterone plasms levels were present, with reappearance of an aldosterone postural response. Plasma renin activity and aldosterone plasma levels normalized I month later, with reappearance also of a plasma renin activity postural response and maintenance of normal potassium plasma levels even on a high sodium and normal potassium diet. The patient has remained hypertensive, although lower antihypertensive drug dosages have been employed. After 17 months, normal biochemical, hormonal and morphological findings were still present. Thus, we suggest PEI-CT as a further alternative approach to surgery in the management of carefully selected patients with APA.

Riccardo Rossi, Chair of Endocrinology, "Federico II" University of Naples, via Sergio Pansini 5, 80131 Naples, Italy
Insulin-like growth factors I and II in healthy women with and without established osteoporosis
Authors: Ravn P , Overgaard K , Spencer EM , Christiansen C
Published: December 2008

Ravn P, Overgaard K, Spencer EM, Christiansen C. Insulin-like growth factors I and II in healthy women with and without established osteoporosis. Eur J Endocrinol 1995;132:313–9. ISSN 0804–4643

We measured serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) by radioimmunoassay in 107 healthy women aged 28–78 years and in 116 women with established osteoporosis. The women with established osteoporosis were randomized to a 1-year double-blind, placebo-controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p < 0.001) as compared to women above that age. For women more than 35 years of age, we found no correlation between IGF-I and age (r = 0.02). Correspondingly, we found no significant changes in serum IGF-I in 10 women, who were followed with serial measurements of IGFs every 3 months from 2 years before to 1 year after menopause; IGF-II revealed no correlation with age (r = 0.04). In the group of 116 women with established osteoporosis, IGF-I was 30% lower (p < 0.01) as compared to a group of 19 height-, weight- and age-matched nonfractured women (mean age 64 years). The IGF-II levels were equal in the two groups. Over the 1-year therapeutic intervention period, an increase in IGF-I of 13–15% (p < 0.05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis.

Pernille Ravn, Center for Clinical & Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark
Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995)
Authors: Caron Philippe , Cogne Muriel , Gusthiot-Joudet Beatrice , Wakim Saria , Catus France , Bayard Francis
Published: December 2008

Caron P, Cogne M, Gusthiot-Joudet B, Wakim S, Catus F, Bayard F. Intramuscular injections of slowrelease lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995). Eur J Endocrinol 1995;132:320–5. ISSN 0804–4643

Nine acromegalic patients (five females and four males), mean age 50 ± 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200–600 μg/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 μg/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20–30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy. Slow-release lanreotide was well tolerated except for minor digestive problems during the early days of treatment or mild pain at the site of injection. Gallbladder echographies were normal during octreotide and lanreotide therapies, except in one patient in whom gallstones occurred during octreotide treatment. In conclusion, this clinical study shows that in acromegalic patients, im injections of slow-release lanreotide (two or three per month) are well tolerated and are as effective as continuous subcutaneous infusion of octreotide in the control of GH hypersecretion. Therefore, slow-release lanreotide would appear to be a useful therapeutic tool to improve the quality of life in patients with acromegaly.

Philippe Caron, Service d'Endocrinologie et Maladies métaboliques, CHU Rangueil, 1 Avenue J Poulhés, 31054 Toulouse Cedex, France
Lack of evidence for pituitary thyrotroph down-regulation after 1 week of oral thyrotrophin-releasing hormone and metoclopramide under conditions of constant peripheral thyroid hormone levels
Authors: Grebe Stefan KG , Delahunt John W , Feek Colin M , Purdie Gordon , Porter David J
Published: December 2008

Grebe SKG, Delahunt JW, Feek CM, Purdie G, Porter DJ. Lack of evidence for pituitary thyrotroph down-regulation after 1 week of oral thyrotrophin-releasing hormone and metoclopramide under conditions of constant peripheral thyroid hormone levels. Eur J Endocrinol 1995;132:331–7. ISSN 0804–4643

We investigated the pituitary thyrotrophin (TSH) response to repeated oral (non-pulsatile) thyrotrophin-releasing hormone (TRH) administration and potential modifying effects of dopamine antagonist treatment under conditions of constant peripheral thyroid hormone levels. In a randomized double-blind crossover trial, seven hypothyroid subjects, euthyroid on l-thyroxine, received 1 week each of oral TRH (40 mg, 12 hourly) plus metoclopramide (10 mg, 8 hourly) and TRH (40 mg, 12 hourly) plus placebo (one capsule, 8 hourly). At the beginning and end of each treatment period five samples of blood for estimation of serum TSH were taken over 1 h before ("baseline") and seven samples over 2 h after the treatment combination was given ("stimulated"). Serum free thyroxine, free triiodothyronine and prolactin levels also were measured. Mean log10 ± sem (log10 mIU/l) "baseline" serum levels TSH were −0.177 ± 0.183 (median 0.345 mIU/l (untransformed); range (r) 0.03–10.11 mIU/l; first quartile (lq) 0.22 mIU/l; third quartile (3q) 2.48 mIU/l) before and 0.182 ± 0.107 (median 1.385 mIU/l; r = 0.45–19.8 mIU/l; lq = 0.9 mIU/l; 3q = 1.78 mIU/l) after 1 week of treatment (p < 0.02). There were no significant differences between oral TRH plus metoclopramide and oral TRH plus placebo. Peripheral thyroid hormone levels and the "stimulated" TSH response (expressed as area under curve after TRH and metoclopramide or placebo; min · log10 mIU/l) remained unchanged after 1 week. In the absence of changes in peripheral thyroid hormone levels, oral TRH over 1 week may not result in down-regulation of anterior pituitary thyrotrophs. This suggests that pulsatility of TRH release be of minor importance only in the hypothalamic pituitary thyroid regulation of TSH release.

Stefan KG Grebe, Department of Medicine, Wellington School of Medicine, Wellington, New Zealand
Relaxin triggers calcium transients in human granulosa-lutein cells
Authors: Mayerhofer Artur , Engling Reiner , Stecher Brigitte , Ecker Axel , Sterzik Karl , Gratzl Manfred
Published: December 2008

Mayerhofer A, Engling R, Stecher B, Ecker A, Sterzik K, Gratzl M. Relaxin triggers calcium transients in human granulosa-lutein cells. Eur J Endocrinol 1995;132:507–13. ISSN 0804–4643

Although the peptide hormone relaxin is synthesized by the human corpus luteum in vivo, its potential to serve as a local factor in the regulation of luteal function is not clear. Using an enzyme-linked immunosorbent assay for human relaxin, we detected relaxin in the culture medium of human granulosa-lutein cells as early as after 6 days in culture. Moreover, 1 × 105 IU/l human chorionic gonadotropin stimulated relaxin release about fourfold during a 48-h incubation on culture days 6–8 (and 7–9), but not earlier (on days 1, 3 and 4). The stimulatory action of human chorionic gonadotropin on progesterone release was not influenced by relaxin, and relaxin alone was without stimulatory effect. However, human recombinant relaxin (between 0.1 and 12.5 μg/l) increased intracellular free Ca2+ basal levels to maximal peak levels exceeding 1000 nmol/l in about 64% of all tested cells (N = 168) with no obvious dependency on the culture day. The relaxin-induced Ca2+ signal was not affected by removal of extracellular Ca2+. As depletion of intracellular Ca2+ stores by ionomycin rendered the cells unresponsive to relaxin or diminished their ability to respond, these results point to an intracellular source of the Ca2+ signal. In summary, our data indicate the presence of a functional relaxin receptor on human granulosa-lutein cells, which is linked to Ca2+ release from intracellular stores.

Manfred Gratzl, Anatomisches Institut der Technischen Universität München, Biedersteiner Strasse 29, D-80802 Munich, Germany
Decrease of incidence of toxic nodular goitre in a region of Switzerland after full correction of mild iodine deficiency
Authors: Baltisberger Benedikt L , Minder Christoph E , Bürgi Hans
Published: December 2008

Baltisberger BL, Minder CE, Bürgi H. Decrease of incidence of toxic nodular goitre in a region of Switzerland after full correction of mild iodine deficiency. Eur J Endocrinol 1995;132:546–9. ISSN 0804–4643

In 1980 the iodide content of salt was increased in Switzerland from 7.5 to 15 mg/kg. This raised the mean urinary iodine excretion from 90 (indicating mild iodine deficiency) to 150 μg/g creatinine. We examined whether this public health measure was followed by a change of the incidence of hyperthyroidism in a defined catchment area of 109 000 persons. Except for a 27% rise in the first year of the new salt, the total incidence of hyperthyroidism declined steadily to reach 44% of the control level in 1988/89. This was due to a decrease mostly of toxic nodular goitre (minus 73%), less so of Graves' disease (minus 33%). We conclude that correction of mild iodine deficiency has beneficial effects on the incidence of hyperthyroidism, contrary to what is seen initially after correction of severe deficiency.

H Bürgi, Department of Medicine, Bürgerspital, CH-4500 Solothurn, Switzerland
Improved dose concept for radioiodine therapy of multifocal and disseminated functional thyroid autonomy
Authors: Reinhardt Michael , Emrich Dieter , Krause Thomas , Bräutigam Peter , Nitzsche Egbert , Blattmann Hildegard , Schümichen Carl , Moser Ernst
Published: December 2008

Reinhardt M, Emrich D, Krause T, Bräutigam P, Nitzsche E, Blattmann H, Schümichen C, Moser E. Improved dose concept for radioiodine therapy of multifocal and disseminated functional thyroid autonomy. Eur J Endocrinol 1995;132:550–6. ISSN 0804–4643

The present study analyzes the improvement of the outcome of radioiodine therapy in non-immunogenic hyperthyroidism by adapting the target dose to the 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) prior to radioiodine therapy. The TcTUs is a substitute for the non-suppressible iodine turnover. The 89 patients presented with a basal thyrotropin level of <0.1 mU/l, normal values for free triiodothyronine and thyroxine and with multifocal or disseminated thyroid autonomy. These terms describe the scintigraphic distribution pattern of autonomous iodine turnover. Thirty-two patients had a TcTUs between 1.6 and 3.2% (group A) and 57 had a TcTUs > 3.2% (group B). Fifty-five patients (three of group A and 52 of group B) were treated previously for overt hyperthyroidism with antithyroid drugs. Target doses of 150 and 200 Gy were used in both groups and 300 Gy in group B only. Six months after radioiodine therapy, a basal TSH level of ≥ mU/l as criterion of therapy success was observed in 94% of group A and in 54% of group B. Further differentiation of group B shows an increasing success rate with the target dose used: 45% after 150 Gy, 50% after 200 Gy and 90% after 300 Gy. In patients with a basal TSH level of <0.5 mU/l after radioiodine therapy, the TcTUs was evaluated again. Persistence of functional thyroid autonomy, defined as TcTUs > 1.6%, was found in 89% (one patient of group A, 24 patients of group B) and still observed a high extent of autonomous function in 25% of them, evidenced by a TcTUs > 3.2% (seven patients of group B, target doses of 150 or 200 Gy). No case of overt hypothyroidism was observed within the first 6 months after radioiodine therapy and no difference was found in therapy outcome between multifocal and disseminated thyroid autonomy. As a consequence, the target dose should be adapted to the TcTUs prior to radioiodine therapy in the range of 150–300 Gy to the total thyroid gland.

Michael Reinhardt, Abteilung Nuklearmedizin, Radiologische Universitätsklinik, Hugstetter Straße 55. 79106 Freiburg im Breisgau, Germany
CV 205-502 treatment in therapy-resistant acromegalic patients
Authors: Lombardi Gaetano , Colao Annamaria , Ferone Diego , Sarnacchiaro Francesca , Marzullo Paolo , Sarno Antonella Di , Rossi Emanuela , Merola Bartolomeo
Published: December 2008

Lombardi G, Colao A, Ferone D, Sarnacchiaro F, Marzullo P, Di Sarno A, Rossi E, Merola B. CV 205-502 treatment in therapy-resistant acromegalic patients. Eur J Endocrinol 1995;132:559–64. ISSN 0804–4643

The growth hormone (GH) inhibitory effect of CV 205-502 was evaluated during acute and 3-month administration, alone or in combination with octreotide, in 12 therapy-resistant acromegalic patients. Although these patients previously had undergone surgery and received chronic therapy with octreotide at 0.3–0.6 mg/day, they still had high GH and insulin-like growth factor I (IGF-I) levels. CV 205-502 (0.15 mg), octreotide (0.1 mg) and placebo were tested acutely. CV 205-502 at the dose of 0.15 mg caused a decrease of GH level (from 34.9 ± 15.1 to 2.7 ± 0.3 μg/l) in 4/12 (33.3%) and completely inhibited prolactin (PRL) secretion in all the patients. Octreotide caused a decrease of GH level (from 37 ± 6.7 to 15.9 ± 3.0 μg/l) without any change of PRL level. The GH and PRL levels were not changed during placebo administration. CV 205-502 at the dose of 0.3 mg/day (chronic test) normalized GH and IGF-I levels in five patients (41.6%: the four responders to the acute test and an additional patient who was a poor responder to acute CV 205-502 administration). The remaining seven patients were subjected to CV 205-502 (0.6 mg/day) and octreotide (0.6 mg/day) in combination for 3 months. In 2/7 patients the combined therapy induced a greater inhibition of GH and IGF-I levels than did each drug when administered alone. The drug was well-tolerated by the 12 patients. In conclusion, CV 205-502 is able to normalize GH and IGF-I levels and to improve clinical symptoms in certain acromegalic patients resistant to other therapeutic approaches. CV 205-502 can, therefore, be considered an effective alternative in the medical management of acromegaly when the first choices, surgery and octreotide, fail to resolve GH hypersecretion.

Gaetano Lombardi, via G. Santacroce 40/a, 80129 Napoli, Italy
A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control
Authors: Spiess K , Sachs G , Pietschmann P , Prager R
Published: December 2008

Spiess K, Sachs G, Pietschmann P, Prager R. A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control. Eur J Endocrinol 1995;132:580–6. ISSN 0804–4643

This paper reports the results of a prospective controlled trial of a program addressing reduction of onset distress and better future adaptation in adults who were enrolled at the time of diagnosis of type I diabetes mellitus. Patients were assigned randomly to either standard intensive treatment and patient education with the distress reduction program (N = 10) or to standard intensive treatment and patient education without this program (N = 13). Prospective follow-up of patients with multiple validated measures of treatment outcome showed less anxious coping behavior, less depression and less denial at the 9-month follow-up and less denial at the 15-month follow-up in the group with the distress reduction program, but no differences in metabolic control between the two groups at any time. We conclude that our program has a positive impact on the crisis at diabetes onset; the lower denial in the treatment group may lead to improved regimen adherence in the long term.

Klaus Spiess, Institute of Medical Psychology, University of Vienna, Severingasse 9, A-1090-Vienna, Austria
Acute changes in biliary excretion of reverse triiodothyronine in rats after insulin-induced hypoglycemia: effect of glucose, verapamil, cycloheximide and actinomycin D
Authors: Langer Pavel , Gschwendtová Klaudia
Published: December 2008

Langer P, Gschwendtová K. Acute changes in biliary excretion of reverse triiodothyronine in rats after insulin-induced hypoglycemia: effect of glucose, verapamil, cycloheximide and actinomycin D. Eur J Endocrinol 1995;132:618–21. ISSN 0804–4643

Biliary excretion of reverse triiodothyronine (rT3) was estimated in rats during hypoglycemia induced by a 10-min infusion of 1 U of insulin (INS) and for the following 5 h. During that period an increase in biliary rT3 was found. This was seen also during the infusion of exogenous glucagon (10 μg in 1.2 ml of saline per 1 h for 5 h) given independently of INS. The infusion of glucose (1 g/kg per 50 min or 2 g/kg per 110 min) following INS infusion delayed the increase in rT3. The increase in rT3 was prevented by actinomycin D (1 mg/kg) when injected before (90 min), but not after (30 min) INS, and also by cycloheximide (2.5 mg/kg) injected immediately before INS. The same dose of cycloheximide also prevented a similar increase of rT3 during the infusion of exogenous glucagon. Verapamil (5 mg/ kg divided into five doses per 4 h) blunted the increase of rT3. These data indicate that following INS injection counter-regulatory hormones may be responsible for the increased production of rT3; this altered metabolic activity apparently is dependent on protein synthesis.

Pavel Langer, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, 833 06 Bratislava, Slovakia
[3 H]Naloxone binding sites in porcine ovarian follicles and corpora lutea during the ovarian cycle
Authors: Hamada Hiroko , Kishioka Shiroh , Yamoto Mareo , Nakano Ryosuke
Published: December 2008

Hamada H, Kishioka S, Yamoto M, Nakano R. [3H]Naloxone binding sites in porcine ovarian follicles and corpora lutea during the ovarian cycle. Eur J Endocrinol 1995;132:622–6. ISSN 0804–4643

We demonstrated the presence of opioid receptors in the porcine ovary using [3 H]naloxone. We also examined the change in the number of opioid receptors during follicular maturation. In addition, we found specific binding of [3H]naloxone in the porcine ovary using naloxone, β-endorphin, methionine-enkephalin and dynorphin. The binding of [3H]naloxone to porcine granulosa cells and the 2000-g subcellular fraction of corpora lutea was examined to demonstrate the presence of specific [3H]naloxone binding in the porcine ovary. Binding of [3H]naloxone to porcine granulosa cells was displaced by cold naloxone and β-endorphin but not by dynorphin and methionine-enkephalin. A similar phenomenon was also demonstrated in the 2000 g subcellular fraction of porcine corpora lutea. However, Scatchard analyses revealed a single class of high-affinity (Kd = 28.5 × 10−9 mol/l) and low-capacity binding sites (Bmax = 30.5 fmol/5 × 106 cells) in porcine granulosa cells. Similar binding parameters were obtained in the 2000-g subcellular fraction of porcine luteal tissue (Kd = 28.3 × 10−9 mol/l, Bmax = 59.3 nmol/kg protein). [3H]Naloxone binding sites in the porcine ovary showed binding characteristics similar to those of opioid receptors in other organs like brain, uterus and placenta. Furthermore, we demonstrated that the specific binding sites of [3H]naloxone in porcine granulosa cells decreased during follicular maturation. Opioid receptors have been detected in the uterus, placenta and Sertoli cell cultures in some species. However, there is no detailed study on opioid receptors in granulosa cells and luteal tissues in any species. Our data suggest a relationship between folliculogenesis and ovarian opioid peptides. The opioid system may participate in the regulation of follicular maturation.

Hiroko Hamada, Department of Obstetrics and Gynecology, Shichibancho 27, Wakayama 640, Japan
Inhibition of the luteinizing hormone-dependent induction of cholesterol side chain cleavage enzyme in immature rat Leydig cells by Sertoli cell products
Authors: van Haren Lizzy , Flinterman J Franny , Rommerts Focko FG
Published: December 2008

Van Haren L, Flinterman JF, Rommerts FFG. Inhibition of the luteinizing hormone-dependent induction of cholesterol side chain cleavage enzyme in immature rat Leydig cells by Sertoli cell products. Eur J Endocrinol 1995;132:627–34. ISSN 0801–4643

The modulation of the luteinizing hormone (LH) induction of cholesterol side chain cleavage (CSCC) enzyme in immature rat Leydig cells was studied using rat Sertoli cell-conditioned medium (SCCM), which stimulates short-term endogenous steroid production. Luteinizing hormone increased the CSCC enzyme activity 10-fold in cells cultured for 7 days in the absence of hormones. This enzyme induction was abolished almost completely in the presence of SCCM. The inhibition was dose dependent (halfmaximal effect at 5 mg protein/l) and paralleled by a decrease in the amount of cytochrome P-450sec P-450scc) enzyme. There were no indications for loss of cell viability. The inhibitory action of SCCM could be localized at the level of adenylate cyclase activation and at steps beyond cyclic adenosine monophosphate production. The inhibition was not specific for Sertoli cell products because conditioned media from different cell lines and media from isolated rat hepatocytes displayed similar effects. Trypsin treatment of SCCM destroyed the activity whereas the bioactivity could resist heating for 5 min at 100°C. Generally occurring (growth) factors, such as epidermal growth factor or tumor necrosis factor α, may have contributed to the observed inhibitory effects of SCCM. These inhibitory effects of Sertoli cell products in vitro are in contrast to stimulatory effects of Sertoli cells on Leydig cell steroidogenesis in vivo after FSH administration.

Focko FG Rommerts, Department of Endocrinology & Reproduction, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands
Interactions between liver nuclear proteins and the human insulin-like growth factor binding protein 1 promoter in the course of development
Authors: Babajko S
Published: December 2008

Babajko S. Interactions between liver nuclear proteins and the human insulin-like growth factor binding protein 1 promoter in the course of development. Eur J Endocrinol 1995;132:635–41. ISSN 0804–4643

Insulin-like growth factor binding proteins (IGFBPs) modulate the bioavailability of the IGFs. Among the six IGFBPs known to date, IGFBP-1 is the most tissue-specific, its expression being limited to the liver and the endometrium. In the liver, IGFBP-1 gene expression is maximal during the perinatal period, with its peak corresponding to a transient rise in gene transcription activity. In this study, interactions between rat liver nuclear proteins and the human IGFBP-1 promoter have been analysed in the course of development, using in vitro DNase I protection and mobility shift assays. Only the interactions between DNA and proteins localized between nt –305 and –268 varied through the period studied (16 days in utero to 70 days postnatally). Three proteins, named Pa, PCI and PC2, interacted with sequences between nt –295 and –285, nt –305 and –295 and nt –285 and –268, respectively. There was a marked perinatal increase in phenotype expression of Pa, which was parallel to that in IGFBP-l gene transcription activity. In addition, DNA-Pa interactions and DNA-PC2 interactions were mutually exclusive. These results suggest that the interaction of Pa with its target sequence(s) prevent PC2 binding and thereby contribute towards increased IGFBP-l gene transcription.

Sylvie Babajko, INSERM U.142, Hôpital Saint Antoine, 184 rue du Faubourg St. Antoine, 75571 Paris Cedex 12, France
Urinary excretion rate of ceruloplasmin in non-insulin-dependent diabetic patients with different stages of nephropathy
Authors: Yamazaki Masatoshi , Ito Seiki , Usami Akio , Tani Nagayuki , Hanyu Osamu , Nakagawa Osamu , Nakamura Hiroshi , Shibata Akira
Published: December 2008

Yamazaki M, Ito S, Usami A, Tani N, Hanyu 0, Nakagawa O. Nakamura H, Shibata A. Urinary excretion rate of ceruloplasmin in non-insulin-dependent diabetic patients with different stages of nephropathy. Eur J Endocrinol 1995;132:681–7. ISSN 0804–4643

The level of ceruloplasmin, which is a more negatively charged protein than albumin, was measured by an immunoradiometric assay in timed overnight urine and serum samples from patients with non-insulin-dependent diabetes mellitus and healthy controls. None of the plasma proteins examined showed any cross-reactivity in this assay. A linear correlation was seen between the ceruloplasmin level and the serial dilution of the sample. Western blot analysis using concentrated urine samples showed that the molecular weight of ceruloplasmin in the urine sample was the same as that of ceruloplasmin in the serum and standard samples. These findings indicated that the substance detected by this assay was truly ceruloplasmin. The urinary ceruloplasmin excretion rate (CER) and clearance of ceruloplasmin increased in parallel with the progression of albuminuria. The highest CER was found in macroalbuminuric patients, followed by micro- and normoalbuminuric patients and the healthy control subjects, the differences between the groups being significant. In view of the fact that the isoelectric point of ceruloplasmin (4.4) is more acidic than that of albumin, the present findings suggested that an enhanced CER was due either to the alteration of charge selectivity in the glomerular basement membrane with unaltered tubular function or to a defect of the non-discriminatory pores (shunt pathway) with unaltered tubular function.

Seiki Ito, Division of Gerontology, Akita University Hospital, 1-1-1 Hondou, Akita City, Japan 010
Cardiovascular effects of long-term l-thyroxine therapy for Hashimoto's thyroiditis in children and adolescents
Authors: Radetti Giorgio , Paganini Claudio , Crepaz Roberto , Pittscheider Walter , Gentili Lino
Published: December 2008

Radetti G, Paganini C, Crepaz R, Pittscheider W, Gentili L. Cardiovascular effects of long-term l-thyroxine therapy for Hashimoto's thyroiditis in children and adolescents. Eur J Endocrinol 1995;132:688–92. ISSN 0804–4643

Morphology and function of the left ventricle were evaluated by echo and Doppler examination in 16 females affected by Hashimoto's thyroiditis. aged 13.3 (4.5) years (range 7.9–24.6). They were on l-thyroxine (l-T4) treatment for a period of 2.8 (2.8) years (range 0.8–7.6) with a mean daily dose of 77 (18) μg/m2. Left ventricular mass, systolic and diastolic function, cardiac output and systemic vascular resistance did not differ from a control group matched for age, sex and body size. A further analysis of the patients according to thyrotrophin serum levels (less or more than 0.1 mU/l) gave similar results. Moreover, no relationship was found between echocardiographic findings and age, l-T4 daily doses, duration of treatment and serum level of thyroid hormones. We can therefore conclude that chronic l-T4 treatment for Hashimoto's thyroiditis at the given doses did not affect cardiac function and morphology in children and adolescents; however, a longer follow-up is needed before confirming the safety of this therapy in the long term.

Giorgio Radetti, Department of Paediatrics, Regional Hospital of Bolzano, via L Boehler no. 5, 39100 Bolzano, Italy
Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency
Authors: Leal-Cerro A , Garcia E , Astorga R , Casanueva FF , Dieguez C
Published: December 2008

Leal-Cerro A, Garcia E, Astorga R, Casanueva FF, Dieguez C. Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency. Eur J Endocrinol 1995;132:712–5. ISSN 0804–4643

In recent years the health problems of adults with growth hormone deficiency (GHD) and the benefits of GH replacement therapy have received considerable attention. However, the reliability of conventional GH tests in the assessment of pituitary GH reserve in this group of patients is still controversial. In this study, we assessed GH secretion after the combined administration of GH-releasing hormone (GHRH) (1 μg/kg iv) and GH-releasing peptide 6 (GHRP-6, 1 μg/kg iv) in adult patients diagnosed with GHD by conventional GH testing, and correlate this response with insulin-like growth factor I levels. Twenty-one subjects (13 male, 8 female) with long-standing diagnosis of GHD aged 21–54 years were studied. In 13 subjects GH responses to GHRH plus GHRP-6 were markedly reduced (peak GH response <10 mU/I), whereas in the remaining eight the response was greater (range 11–100 mU/l), In conclusion, our data show that combined administration of GHRH plus GHRP-6 elicited a significant increase in plasma GH levels in about 40% of patients diagnosed with GHD by conventional GH testing.

C Dieguez, PO Box 563, 15700 Santiago de Compostela, Spain
Clinical usefulness of thyroid-stimulating antibody measurement using Chinese hamster ovary cells expressing human thyrotropin receptors
Authors: Murakami Masami , Miyashita Kazuya , Kakizaki Satoru , Saito Shuichi , Yamada Masanobu , Iriuchijima Tokuji , Takeuchi Toshiyuki , Mori Masatomo
Published: December 2008

Murakami M, Miyashita K, Kakizaki S, Saito S, Yamada M, Iriuchijima T, Takeuchi T, Mori M, Clinical usefulness of thyroid-stimulating antibody measurement using Chinese hamster ovary cells expressing human thyrotropin receptors. Eur J Endocrinol 1995;133:80–6. ISSN 0804–4643

Human thyrotropin (TSH) receptors were expressed in Chinese hamster ovary (CHO) cells using eukaryotic expression plasmid pCXN2, which contains β-actin promoter. We measured cAMP stimulation in CHO cells expressing human TSH receptors (CHO-hTSH-R cells) by immunoglobulin G (IgG) of patients with Graves' disease and Hashimoto's thyroiditis, and compared the results with a conventional thyroid-stimulating antibody (TS-Ab) assay using porcine thyroid cells and a TSH-binding inhibiting immunoglobulin (TBII) assay. Nineteen untreated patients with Graves' disease, including a case who developed hyperthyroidism after interferon -α therapy for chronic hepatitis C, and 13 treated patients with Graves' disease, 10 patients with Hashimoto's thyroiditis and 8 control subjects were studied. In 19 untreated patients with Graves' disease, 17 patients showed positive CHO-hTSH-R cell stimulation, 11 patients showed positive porcine thyroid cell stimulation and 15 patients showed positive TBII. All the untreated patients showed positive results in at least one assay, Although significantly positive correlations were observed among CHO-hTSH-R cell stimulation, porcine thyroid cell stimulation and TBII activities, the IgG of several patients showed significant discrepancy in the assay results. In a patient with interferon-induced hyperthyroidism only CHO-hTSH-R cell stimulation was positive, while porcine thyroid cell stimulation and TBII were negative. After the treatment with propylthiouracil for 6 months, CHO-hTSH-R cell stimulation became negative. The IgG of patients with Hashimoto's thyroiditis did not show significant stimulation of CHO-hTSH-R cells. These results suggest that the CHO-hTSH-R cell stimulation assay is clinically useful for the diagnosis and follow-up of patients with Graves' disease.

Masami Murakami, First Department of Internal Medicine, Gunma University, School of Medicine, Maebashi 371, Japan