bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment
Authors: Antoniazzi Franco , Bertoldo Francesco , Zamboni Giorgio , Valentini Roberta , Sirpresi Stefania , Cavallo Luciano , Adami Silvano , Tato Luciano
Published: December 2008

Antoniazzi F, Bertoldo F, Zamboni G, Valentini R, Sirpresi S, Cavallo L, Adami S, Tatò L. Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment. Eur J Endocrinol 1995;133:412–7. ISSN 0804–4643

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9–8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)–insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months. Before therapy, lumbar spine and radius bone mass were high for chronological age but appropriate for bone age; after 12 months of treatment, bone mass in the lumbar spine, but not in the radius, had decreased significantly. In our patients, regression of pubertal development was associated with a reduction of trabecular bone mass, which appears to be the primary consequence of GnRHa therapy and possibly related to decreased GH secretion.

Franco Antoniazzi, Clinica Pediatrica, Università di Verona, Policlinico Borgo Roma, 1-37134 Verona, Italy
Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts
Authors: Laudat Antoine , Blum Laurent , Guéchot Jérôme , Picard Odile , Cabane Jean , Imbert Jean Claude , Giboudeau Jacqueline
Published: December 2008

Laudat A, Blum L, Guechot J, Picard O, Cabane J, Imbert JC, Giboudeau J. Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts. Eur J Endocrinol 1995;133:418–24. ISSN 0804–4643

Serum sex hormone-binding globulin (SHBG), testosterone, non-SHBG-bound testosterone, androstenedione, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and cortisol were measured in 58 homosexual men seropositive for human immunodeficiency virus (HIV), all clinically asymptomatic (Centers for Disease Control 1993 classification stage A). The HIV patients were divided into four groups according to the CD4 lymphocyte count—group 1 (more than 500/μl, N= 14), group 2 (between 350 and 500/μl, N= 16), group 3 (between 200 and 349/μl, N = 22) and group 4 (less than 200/μl, N = 6)—and compared with 11 antibody-negative men as controls. The SHBG levels were significantly increased in groups 1, 2, 3 (p < 0.01) and 4 (p < 0.05) compared with controls, with no differences between groups of patients. Compared with controls, testosterone concentrations were significantly lower in group 4 (p < 0.05) and non-SHBG-bound testosterone levels were significantly lower in groups l(p < 0.05), 2 (p < 0.01), 3 (p < 0.001) and group 4 (p < 0.001); DHT and androstenedione levels were significantly lower in group 4 (p < 0.05) and DHEA levels were significantly lower in group 2, group 3 (p < 0.01) and group 4 (p< 0.05) than in controls. Cortisol levels were significantly increased in groups 1 and 4 (p < 0.05) and FSH and LH concentrations were not significantly higher in HIV-infected men than in controls. Also, the DHEA, androstenedione, non-SHBG-bound testosterone and DHT levels were correlated with CD4 cell counts, showing that hypogonadism occurs as the CD4 lymphocytes decrease. A strong reverse correlation between CD4 cell counts and cortisol/DHEA ratios (p < 0.001) confirms the alterations in adrenal steroid secretion, with a shift from androgen to glucocorticoid production as the disease progresses. These data show that in asymptomatic HIV-infected patients serum SHBG levels increase independently of CD4 cells counts, even in patients with undiminished CD4 cell counts; an alteration in serum androgen occurs as the CD4 cell counts decrease; and the cortisol/DHEA ratios increase as the CD4 cell counts decrease, resulting from alterations in adrenal secretion with both a decrease in serum DHEA levels correlated with CD4 cell counts and a slight increase in cortisol levels.

Jérôme Guéchot, Laboratoire de Biochimie-Hormonologie, Hôpital Saint-Antoine, 184 rue du Faubourg, Saint-Antoine, 75571 Paris Cedex 12, France
Combined pyridostigmine–thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men
Authors: Yang Inmyung , Woo Jeongtaek , Kim Sungwoon , Kim Jinwoo , Kim Youngseol , Choi Youngkil
Published: December 2008

Yang I, Woo J, Kim S, Kim J, Kim Y, Choi Y. Combined pyridostigmine–thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men. Eur J Endocrinol 1995;133:457–62. ISSN 0804–4643

Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60–120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 μg of TRH iv; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 μg of octreotide (SMS) iv; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST–TRH test.

Inmyung Yang, Division of Endocrinology, Department of Internal Medicine, Kyunghee University School of Medicine, 1 Hoiki-dong, Dongdaemoon-ku, Seoul, 130–702, Korea
Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin secretion and intracellular calcium concentration in rat pituitary
Authors: Roussel Jean-Paul , Grazzini Eric , Guipponi Michel , Astier Hélène
Published: December 2008

Roussel J-P, Grazzini E, Guipponi M, Astier H. Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin secretion and intracellular calcium concentration in rat pituitary. Eur J Endocrinol 1995;133:489–98. ISSN 0804–4643

Amiodarone (AM) and its major metabolite desethylamiodarone (DEA) are structurally similar to biologically active thyroid hormones. Amiodarone therapy is frequently associated with impairment of thyrotropic function, whose mechanisms are still controversial. Besides its effect on nuclear thyroid hormone binding, AM is able to displace dihydropyridine (DH) binding on membrane preparations from several tissues. By perifusing rat pituitary fragments and measuring thyrotropin (TSH) release we examined: the effect of AM on Ca2+-dependent and DHP-sensitive potentiation of the TSH response to thyrotropin-releasing hormone (TRH) induced by either triiodothyronine (T3, perifused for only 30 min before a TRH pulse) or by the prepro-TRH peptide 160–169 (PS4): and the effect of DEA on trh-induced TSH response in the presence or absence of the DHP nifedipine. We show that AM reverses T3 or PS4 potentiation of the TSH response to TRH; this effect is specific because AM does not modify does potentiation of that response. In contrast, DEA significantly potentiates the TSH response to TRH and the DHP nifedipine reverses that potentiation. We also tested whether Am would change the acute T3-induced increase in intracellular Ca2+ concentration by measuring intracellular Ca2+ ([Ca2+])i with fura-2 imaging on primary cultures of pituitary cells. We show that AM reverses the effect of T3 on [Ca2+]i as well as the PS4-induced increase in [Ca2+]i. In contrast, DEA increases [Ca2+]i and nifedipine reverses this effect. Our results suggest that AM and DEA display DHP-like effects on TRH-induced TSH release, behaving either as a Ca2+ channel blocker (AM) or as a Ca2+ channel agonist (DEA).

H Astier, Laboratoire de Neurobiologie Endocrinologique, URA 1197 CNRS, Departement de Biologie-Santé Université de Montpellier 2, Place E. Bataillon, 34095 Montpellier Cedex 05, France
Ascorbate depletion prevents aldosterone stimulation by sodium deficiency in the guinea pig
Authors: Redmann A , Möbius K , Hiller HH , Oelkers W , Bähr V
Published: December 2008

Redmann A, Möbius K, Hiller HH, Oelkers W, Bähr V. Ascorbate depletion prevents aldosterone stimulation by sodium deficiency in the guinea pig. Eur J Endocrinol 1995;133:499–506. ISSN 0804–4643

The concentration of ascorbic acid (vitamin C) in the adrenal cortex is higher than in any other organ. The role of vitamin C in the adrenal cortex is unknown, but data obtained with bovine adrenocortical cells in vitro favour its role as an antioxidant that especially protects aldosterone synthesis from damaging lipid peroxides. Alternatively, vitamin C could act as part of an auxiliary electron transport system for the last step of aldosterone synthesis. The effects of vitamin C depletion on adrenocortical function cannot be studied in the human for ethical reasons, so we subjected different groups of guinea pigs to vitamin C depletion, sodium depletion and combined vitamin C and sodium depletion. Other groups of animals on normal or vitamin C-deficient diets received high-dose adrenocorticotrophin (ACTH) injections for 3 days before sacrifice. Fifteen days of a vitamin C-free diet led to very low vitamin C levels in adrenals, liver and plasma without clear signs of scurvy. At this time, plasma aldosterone and aldosterone secretion by isolated adrenal cells were stimulated significantly by sodium deficiency. Simultaneous vitamin C depletion completely abolished the rise in aldosterone in vivo and in vitro, significantly reduced the conversion of [3H]deoxycorticosterone to [3H]aldosterone and impaired renal sodium conservation. Plasma renin activity (PRA), plasma ACTH and serum potassium were not different in the sodium-depleted and sodium plus vitamin C-depleted groups. Sodium depletion did not affect cortisol. Vitamin C depletion led to a significant increase in plasma cortisol without an increase in ACTH, while in vitro secretion of cortisol was slightly decreased. These findings seem to be due to decreased hepatic cortisol metabolism. Three days of ACTH treatment led to a large increase in plasma cortisol and in vitro cortisol secretion, while plasma aldosterone and in vitro aldosterone secretion (and PRA) were greatly suppressed. This effect of ACTH was not changed by vitamin C depletion. In conclusion, our studies have demonstrated for the first time a permissive role of vitamin C in the adaptation of aldosterone secretion and of sodium excretion to sodium deficiency, which is an important physiological function of aldosterone. The molecular mechanisms by which vitamin C is involved in aldosterone synthesis await further studies.

V Bähr, Freie Universität Berlin, Klinikum Benjamin Franklin, Division of Endocrinology, Department of Medicine, Hindenburgdamm 30, D-12200 Berlin, Germany
Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants
Authors: Hanukoglu Aaron , Fried Daniel , Nakash Ishak , Hanukoglu Israel
Published: December 2008

Hanukoglu A, Fried D, Nakash I, Hanukoglu I. Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants. Eur J Endocrinol 1995;133:552–6. ISSN 0804–4643

To examine steroidogenic responses of the different zones of the adrenal cortex to acute disease we determined the basal and adrenocorticotropin (ACTH)-stimulated levels of cortisol, dehydroepian-drosterone (DHEAS) and aldosterone in 16 infants aged 1–4 months with acute bronchiolities, Fourteen of the infants were retested after recovery. During illness the mean basal levels of cortisol and DHEAS were twice as high as the levels after recovery (370 vs 180 nmol/l and 2.7 vs 1.3 μmol/l, respectively). The mean peak ACTH-stimulated levels of cortisol and DHEAS during illness were 1.5and 2.5-fold higher, respectively, than the levels found after recovery. Although aldosterone secretion was stimulated ⩾ 3-fold by ACTH, illness was not associated with any change in aldosterone secretory capacity. The basal and stimulated levels of both cortisol and DHEAS during illness and after recovery were correlated significantly. Thus, the relative steroidogenic capacities for these two steroids were characteristic of the individual infant and showed constancy over a period of at least several weeks. While the levels of cortisol and aldosterone were not dependent on the age of the infants, both the basal and stimulated levels of DHEAS correlated strongly with age. We conclude that during acute disease the steroidogenic capacity selectively increases in the zones that secrete cortisol and DHEAS (only in infants <3 months) but not in the zona glomerulosa that secretes aldosterone. The DHEAS response may be related to its putative effects to enhance immune responses.

Aaron Hanukoglu, Department of Pediatrics, E. Wolfson Hospital, Holon 58100, Israel
Interactions between angiotensin II and norepinephrine on renin release by juxtaglomerular cells
Authors: Ichihara Atsuhiro , Suzuki Hiromichi , Murakami Marohito , Naitoh Mareo , Matsumoto Akira , Saruta Takao
Published: December 2008

Ichihara A, Suzuki H, Murakami M, Naitoh M, Matsumoto A, Saruta T. Interactions between angiotensin II and norepinephrine on renin release by juxtaglomerular cells. Eur J Endocrinol 1995:133:569–77. ISSN 0804–4643

While the interactions between angiotensin II (Ang II) and norepinephrine (NE) on cardiovascular responses are well known, their effects on renin responses are not. We determined the renin secretion rate (RSR) and intracellular calcium level in juxtaglomerular cells harvested from Sprague-Dawley rats using a radioimmunoassay and a two-dimensional calcium analyzer. The effect of Ang II and NE was inhibitory on RSR and stimulatory on intracellular calcium. The NE-induced RSR response was amplified in the presence of Ang II (20 nmol/l), The NE-induced intracellular calcium response was also potentiated by the Ang II. There was a significant correlation (r = 0.994, p < 0.0001) between the changes in the RSR and those in intracellular calcium levels. Losartan (0.1 μmol/l), an Ang II type I receptor antagonist, blocked the Ang II threshold RSR responses and completely abolished the Ang II-related enhancements. The exclusion of calcium from the buffer reduced the maximal RSR response to NE but did not prevent the enhancement, suggesting the importance of the mobilization of intracellular calcium in the mechanism. The Ang Il-induced RSR was amplified in the presence of NE (0.2 μmol/l), The Ang II-induced intracellular calcium response was also potentiated by the NE. A significant correlation (r = 0.996, p < 0.0001) between the changes in the RSR and the changes in intracellular calcium levels was also noted. Prazosin (1 μmol/l), an α1-adrenoceptor antagonist, blocked the NE threshold RSR responses and abolished the agonist-related enhancements. The calcium-free buffer diminished this amplication with a slight decrease in the maximum RSR response to Ang II. In juxtaglomerular cells, Ang II and NE amplified each other's RSR responses via an increase in intracellular calcium levels. These responses were mediated by the activation of Ang II type I receptors and α1-adrenoceptors, respectively.

Takao Saruta, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan
Usefulness of recombinant human prolactin for treatment of poor puerperal lactation in a rat model
Authors: Yoneda Naoto , Irahara Minoru , Saito Seiichiro , Uemura Hirokazu , Aono Toshihiro
Published: December 2008

Yoneda N, Irahara M, Saito S, Uemura H, Aono T. Usefulness of recombinant human prolactin for treatment of poor puerperal lactation in a rat model. Eur J Endocrinol 1995;133:613–7. ISSN 0804–4643

Recombinant human prolactin (r-hPRL) was produced by a line of murine C127 cells transfected with human PRL gene. To assess the biological efficacy of r-hPRL in vivo, we studied its influence on milk secretion using a rat model in which lactation was reduced by bromocriptine treatment. Puerperal rats were injected daily for 9 days after delivery with bromocriptine or bromocriptine plus r-hPRL, and lactational performance was assessed by weighing the pups. The concentrations of rat and human PRL in rat serum were measured by specific radioimmunoassays and the mammary glands were examined on postpartum day 10. Daily injection of bromocriptine (0.1 mg/rat) significantly reduced the endogenous level of rat PRL and impaired the weight gain of the pups. Administration of r-hPRL increased the serum level of human PRL. Daily injections of r-hPRL (50 μg/rat, twice a day) restored lactational performance and significantly increased the weight of the pups. The detrimental effect of bromocriptine on the mammary glands, assessed by both weight and histological appearance, was reversed by administration of r-hPRL. These results demonstrate that r-hPRL is biologically active in vivo and replacement therapy of r-hPRL is effective in improving the lactational performance in bromocriptine-treated rats, and also that r-hPRL may be useful for the treatment of women with poor lactation.

Naoto Yoneda, Department of Obstetrics and Gynecology, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto, Tokushima 770, Japan
Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man
Authors: degli Uberti Ettore C , Ambrosio Maria R , Bondanelli Marta , Transforini Giorgio , Valentini Alberto , Rossi Roberta , Margutti Angelo , Campo Michela
Published: December 2008

degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Valentini A, Rossi R, Margutti A, Campo M. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. Eur J Endocrinol 1995;133:723–8. ISSN 0804–4643

Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60 min infusion of hGAL (80 pmol·kg−1 · min−1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function.

Ettore C degli Uberti, Chair of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy
Familianl dysalbuminemic hyperthyroxinemia in pregnancy
Authors: Sachmechi Issac , Schussler George C
Published: December 2008

Sachmechi I, Schussler GC. Familial dysalbuminemic hyperthyroxinemia in pregnancy. Eur J Endocrinol 1995;133:729–31. ISSN 0804–4643

A 16-year-old pregnant Puerto Rican woman who had been treated for thyrotoxicosis previously was evaluated for goiter, increased total thyroxine (T4) and triiodothyronine (T3) and free T4 estimate, despite a normal thyroid-stimulating hormone (TSH) concentration. These findings are consistent with a TSH-producing pituitary adenoma or the syndrome of generalized thyroid hormone resistance. However, sera from the patient, her mother and subsequently her newborn daughter demonstrated the increased albumin binding of T4 but not T3 that is characteristic of familial dysalbuminemic hyperthyroxinemia (FDH). The free T4 estimate had been elevated artefactually by the increased affinity of FDH albumin for the analog in a one-step assay. The T3 and T4 concentrations were increased by pregnancy and T4 was increased further by FDH. This first report of FDH recognized during pregnancy emphasizes that the effects of pregnancy on thyroid hormone and TSH concentrations complicate the diagnosis of FDH. It is particularly important to distinguish this benign condition from thyrotoxicosis during pregnancy, because inappropriate treatment may affect fetal development.

Issac Sachmechi, Dept. of Medicine, Queens Hospital Center, 82-68 164th Street, Queens, New York, USA
Melatonin affects proopiomelanocortin gene expression in the immune organs of the rat
Authors: Wajs Ewa , Kutoh Eiji , Gupta Derek
Published: December 2008

Wajs E, Kutoh E, Gupta D. Melatonin affects proopiomelanocortin gene expression in the immune organs of the rat. Eur J Endocrinol 1995;133:754–60. ISSN 0804–4643

The induction of opioid peptides derived from cells of the immune system is postulated to be the main mechanism involved in the immunomodulatory role of melatonin. In this study, it has been demonstrated for the first time that melatonin can act on the level of proopiomelanocortin (POMC) gene expression. The effect of the pineal hormone, administered in late-afternoon subcutaneous injections, was studied in the immune organs of adult male Wistar rats by means of a highly sensitive reverse transcription-polymerase chain reaction method (RT-PCR), followed by polyacrylamide gel electrophoresis and densitometric analysis of the bands. It was demonstrated that melatonin stimulates the expression of the 3rd exon of the POMC gene in the lymph nodes and in bone marrow. No significant effects of the pineal hormone were observed in the spleen and thymus. The study establishes that the formation of short POMC transcripts in the bone marrow and lymph nodes may be upregulated by melatonin. Moreover, the pineal hormone exerts its effect without antigenic stimulation.

Ewa Wajs, Section Pediatric Endocrinology, Children's Hospital, The University of Tübingen, Rümelinstr. 23, 72070 Tübingen, Germany
Characterization of adhesion receptors on cultured microvascular endothelial cells derived from the retroorbital connective tissue of patients with Graves' ophthalmopathy
Authors: Heufelder Armin E , Scriba Peter C
Published: December 2008

Heufelder AE, Scriba PC. Characterization of adhesion receptors on cultured microvascular endothelial cells derived from the retroorbital connective tissue of patients with Graves' ophthalmopathy. Eur J Endocrinol 1996:134:51–60

T lymphocytes have been demonstrated recently to play an important role in the pathogenesis and propagation of Graves' ophthalmopathy (GO). Recruitment of T cells to the retroorbital tissue in GO involves the activation of certain adhesion molecules both in the vascular endothelium and in the extravascular connective tissue within the retroorbital space. To characterize the interactions between orbital endothelial cells (OECs) and circulating T cells in vitro, we designed a two-step immunopurification procedure with bead-immobilized Ulex europaeus I lectin and anti-human endothelial cell antigen (CD3I) monoclonal antibody for rapid and reproducible isolation of highly pure microvascular endothelial cell populations from small quantities of retroorbital connective tissue. Endothelial origin of the resulting cell populations was confirmed by positive immunoreactivity for von Willebrand factor. CD 3 I and thrombomodulin. Under baseline conditions, GO-OECs, but not normal OECs, expressed intercellular adhesion molecule 1 (ICAM-1) and CD44 immunoreactivity but no immunoreactivity for endothelial leukocyte adhesion molecule I (ELAM-1) and vascular cell adhesion molecule I (VCAM-1) was detected. Exposure of GO-OEC and normal OEC monolayers to interferon γ, interleukin 1 α and tumor necrosis factor α resulted in marked up-regulation of immunoreactivity for ICAM-1 and in induction of ELAM-1 and VCAM-1. Blocking experiments using monoclonal antibodies directed against various adhesion molecules demonstrated that interactions between matched activated T lymphocytes and OECs were mediated by integrin-dependent ICAM-1/leukocyte function-associated antigen 1 (LFA-1): VCAM-1/very late antigen 4 (VLA-4)) and integrin-independent (CD44) pathways, and revealed marked differences when comparing GO-OECs and normal OECs. In conclusion, the availability of OECs from affected retroorbital tissue of patients with GO provides a valuable tool for studying further the mechanisms responsible for orbit-specific lymphocyte recruitment in GO.

Armin E Heufelder, Molecular Thyroid Research Unit, Medizinische Klinik, Klinikum Innenstadt, Ziemssenstrasse 1, 80336 München, Germany
Effects of castration on luteinizing hormone secretion and response to gonadotrophin-releasing hormone in sheep infected with Trypanosoma congolense
Authors: Mutayoba BM , Eckersall PD , Jeffcoate IA , Harvey MJA , Cestnik V , Holmes PH
Published: December 2008

Mutayoba BM, Eckersall PD, Jeffcoate IA, Harvey MJA, Cestnik V. Holmes, PH. Effects of castration on luteinizing hormone secretion and response to gonadotrophin-releasing hormone in sheep infected with Trypanosoma congolense, Eur J Endocrinol 1996:134:115–22. ISSN 0804–4643

The effects of trypanosomiasis on the endocrine function of the hypothalamo-pituitary-gonadal axis were investigated before and after castration of Scottish Blackface rams infected with Trypanosoma congolense and uninfected controls. Blood samples were collected at 15-min intervals for 6 h before and at 10,20,40, 60, 80, 100 and 120 min after injection of synthetic gonadotrophin-releasing hormone (GnRH, 20 μg iv) 2 days before infection and 26 and 54 days after infection, with castration being performed 28 days after infection. Mean luteinizing hormone (LH) pulse amplitude was higher (3.3 ± 0.2 vs 2.6 ± 0.3 ng/ml) and mean plasma testosterone concentration was lower (4.1 ± 0.6 vs 7.6 ±1.2 nmol/l) in infected vs control rams 26 days after infection (p < 0.05). Mean plasma LH concentration and pulse amplitude increased in both groups after castration but both were significantly lower in infected compared to control rams (6.6 ±1.5 and 13.0 ± 2.2 ng/ml, p < 0.01; 7.7 ±0.9 and 11.6 ± 0.9 ng/ml, p < 0.001). respectively. However, LH responses to exogenous GnRH were similar in infected and control rams at each stage of the experiment, suggesting that the smaller increase in plasma LH after castration in infected rams was not caused by reduced responsiveness of the pituitary to GnRH but by alterations in GnRH secretion by the hypothalamus or its transport to the adenohypophysis. These results also demonstrate that impairment of testosterone secretion within 4 weeks of T. congolense infection in sheep may be due to testicular rather than pituitary effects.

IA Jeffcoate, Department of Veterinary Physiology. University of Glasgow Veterinary School, Bearsden, Glasgow G61 1QH. UK
Regulation of mouse placental lactogen secretion by factors secreted from the pituitary in vitro
Authors: Yamaguchi Masaaki , Miyake Akira
Published: December 2008

Yamaguchi M. Miyake A. Regulation of mouse placental lactogen secretion by factors secreted from the pituitary in vitro. Eur J Endocrinol 1996;134:123–7. ISSN 0804–4643

The effect of factors secreted from the pituitary on mouse placental lactogen I (mPL-I) and mPL-II secretion in vitro was examined. Co-culture of mouse placental cells from day 7 of pregnancy with the pituitary cells of the mother significantly stimulated mPL-I secretion but did not regulate mPL-II secretion. The effect on mPL-I secretion was dependent on the number of pituitary cells. The conditioned medium of pituitary cells also significantly stimulated mPL-I secretion but did not regulate mPL-II secretion. The stimulatory effect of mPL-I secretion was dependent on the volume of the conditioned medium. The number of cells containing mPL-I assessed by immunocytochemistry was increased by the co-culture in a cell number-dependent manner. Northern blot analysis for mPL-I indicated that treatment of placental cells with the pituitary-conditioned medium results in an increase of mPL-I gene expression. These findings suggest that factors secreted from the pituitary directly regulate mPL-I secretion, but not mPL-II secretion, before midpregnancy in vivo.

Masaaki Yamaguchi, Department of Obstetrics and Gynecology. Osaka University Medical School, 2-2 Yamadaoka, Suita. Osaka 565, Japan
Restoration of human chorionic gonadotropin response in human myometrial smooth muscle cells by treatment with follicle-stimulating hormone (FSH): evidence for the presence of FSH receptors in human myometrium
Authors: Kornyei JL , Li X , Lei ZM , Rao ChV
Published: December 2008

Kornyei JL, Li X, Lei ZM, Rao ChV. Restoration of human chorionic gondadotropin response in human myometrial smooth muscle cells by treatment with follicle-stimulating hormone (FSH): evidence for the presence of FSH receptors in human myometrium. Eur J Endocrinol 1996;134:225–31. ISSN 0804–4643

Human myometrial smooth muscle cells contain receptors for human chorionic gonadotropin (hCG)/ luteinizing hormone (LH). Exogenous hCG and LH can cause a modest hyperplasia in myometrial smooth muscle cells in culture. This response is lost after about the third subculture of the cells. The present study investigated whether the loss of hCG response could be restored by co-culturing with human follicle stimulating hormone (FSH). The results showed that co-culturing with FSH can indeed restore a modest mitogenic response of hCG. However, FSH alone was not mitogenic. The FSH restoration of hCG response can be blocked by antibodies to FSH or hCG but not by non-specific rabbit IgG. The FSH treatment resulted in an increase of steady state levels of hCG/LH receptor mRNA and protein in myometrial smooth muscle cells. Since the FSH actions could be receptor mediated, we investigated the presence of FSH receptor mRNA transcripts and protein in freshly dispersed myometrial smooth muscle cells. Northern blotting demonstrated that myometrial smooth muscle cells, just as rat ovary, a classical target of FSH action, contain multiple FSH receptor mRNA transcripts. Western immunoblotting demonstrated that myometrial smooth muscle cells also contain a 60 kDa FSH receptor protein just as rat ovary and human granulosa cells used as positive control tissues. The immunocytochemistry also demonstrated that myometrial smooth muscle cells, as rat ovary and human granulosa cells, contain FSH receptor immunostaining. In summary, it is novel that FSH could restore the mitogenic response of hCG in human myometrial smooth muscle cells and these cells contain FSH receptors. These findings may have functional implications for direct regulation of human myometrium not only by hCG/LH but also by FSH.

ChV Rao, Department of Obstetrics and Gynecology, 438 MDR Building, University of Louisville, School of Medicine, Louisville, Kentucky 40292, USA
Human kidney 11β-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?
Authors: Diederich S , Quinkler M , Miller K , Heilmann P , Schöneshöfer M , Oelkers W
Published: December 2008

Diederich S, Quinkler M, Miller K, Heilmann P, Schöneshöfer M, Oelkers W. Human kidney 11βhydroxysteroid dehydrogenase: regulation by adrenocorticotropin? Eur J Endocrinol 1996;134:301–7. ISSN 0804–4643

In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11β-hydroxysteroid dehydrogenase (11β-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11β-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11β-HSD activity was not influenced by incubation with increasing concentrations (10−12–10−9 mol/l) of ACTH (1–24 or 1–39) for 1 h. Among 12 ACTH-dependent steroids tested (10−9–10−6 mol/l), only corticosterone (IC50 = 2 × 10−7 mol/l), 18-OH-corticosterone and 11βOH-androstenedione showed a significant dose-dependent inhibition of 11β-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10−8–10−5 mol/l). A direct inhibitory effect of ACTH on 11β-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11β-HSD Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11β-HSD by ACTH or ACTHdependent steroids, not being substrates of 11β-HSD.

S Diederich, Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany
Obvious mRNA and protein expression but absence of mutations of the RET proto-oncogene in parathyroid tumors
Authors: Kimura Takehiko , Yoshimoto Katsuhiko , Tanaka Chisato , Ohkura Toshihiro , Iwahana Hiroyuki , Miyauchi Akira , Sano Toshiaki , Itakura Mitsuo
Published: December 2008

Kimura T, Yoshimoto K, Tanaka C, Ohkura T, Iwahana H, Miyauchi A, Sano T. Itakura M. Obvious mRNA and protein expression but absence of mutations of the RET proto-oncogene in parathyroid tumors. Eur J Endocrinol 1996;134:314–9. ISSN 0804–4643

The study on the expression of the RET proto-oncogene in parathyroid tumors disclosed obvious mRNA expression by the reverse transcription (RT)-polymerase chain reaction (PCR) method and protein expression by Western blotting. To find out whether mutations in the cysteine-rich regions or tyrosine kinase domain of the RET proto-oncogene are etiological for parathyroid tumorigenesis, sporadic parathyroid adenomas and carcinomas, parathyroid tumors from multiple endocrine neoplasia 1. familial isolated hyperparathyroidism or hereditary hyperparathyroidism-jaw tumor syndrome were screened by PCR-single strand conformation polymorphism and PCR restriction fragment length polymorphism. Missense mutations in the cysteine-rich region, or codons 768 or 918 in the tyrosine kinase domain of the RET proto-oncogene, were not detected in any of the examined cases of parathyroid tumors. These results suggest that mutations of the RET proto-oncogene do not represent a frequent mechanism of tumorigenesis for parathyroid tumors.

Mitsuo Itakura, Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima-city, 770 Japan
Effect of insulin and growth hormone on the synthesis of radiolabelled proteoglycans from cultured human arterial smooth-muscle cells
Authors: Thøgersen Vibeke B , Heickendorff Lene , Ledet Thomas
Published: December 2008

Thogersen VB, Heickendorff L, Ledet T. Effect of insulin and growth hormone on the synthesis of radiolabelled proteoglycans from cultured human arterial smooth-muscle cells. Eur J Endocrinol 1996;134:326–30. ISSN 0804–4643

The present study focuses on the pathogenesis of increased frequency of large-vessel disease in diabetes. The diabetic arterial wall displays characteristic alterations of the extracellular matrix secreted by arterial smooth-muscle cells. The effects of insulin and growth hormone on the synthesis of sulphate-labelled proteoglycans and heparan sulphate proteoglycan were studied. Proteoglycans and heparan sulphate proteoglycan were obtained from the medium and the cell layer of cultured human arterial smooth-muscle cells grown in 5% human serum. Heparan sulphate proteoglycan was quantified using ethanol precipitation combined with specific enzyme degradation. Addition of insulin (0.01, 0.05 and 0.10 mU/ml) induced a significant accumulation of 35S-labelled proteoglycans in the cell layer (2p < 0.005 and 2p < 0.001). The relative amount of cell-associated heparan sulphate proteoglycan increased during insulin stimulation (2p < 0.05). Growth hormone stimulation (5.0 and 10.0 ng/ml) caused a significant decrease in the ratio between heparan sulphate proteoglycan and proteoglycan in the cell layer (2p < 0.02 and 2p < 0.01). whereas the distribution of proteoglycans between the cell layer and the medium was unaltered.

Vibeke Bech Thogersen, Research Laboratory for Biochemical Pathology, Department of Pathology, Aarhus University Hospital, Kommunehospitalet, Nørrebrogade 44, DK-8000, Aarhus C, Denmark
Enhanced expression of transforming growth factor β1 in rat thyroid hyperplasia is thyrotropin induced and time dependent
Authors: Morosini PP , Taccaliti A , Arnaldi G , Simonella G , Petrelli MD , Mancini V , Montironi R , Scarpelli M , Diamanti L , Mantero F
Published: December 2008

Morosini PP, Taccaliti A, Arnaldi G, Simonella G, Petrelli MD, Mancini V, Montironi R, Scarpelli M. Diamanti L, Mantero F. Enhanced expression of transforming growth factor β1 in rat thyroid hyperplasia is thyrotropin induced and time dependent. Eur J Endocrinol 1996:134:373–8. ISSN 0804–4643

Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor β1 TGF-β1) mRNA levels in thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week PTU-1): five after 2 weeks PTU-2): five after 4 weeks PTU-4): five after 8 weeks PTU-8): five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment, PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the thyroid was excised and subdivided into two lobes. Northern analysis for TGF-β1 was performed in one lobe, while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-β1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-β1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4–8. Gene expression of TGF-β1 was also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-β1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-β1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypothyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypothyroidism. The immunohistochemical location of TGF-β1 within the thyrocytes is influenced by mitogen exposure time. A TGF-β1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.

Pierpaolo Morosini, Clinica di Endocrinologia, c/o Ospedale Regionale, Via Conca, 60100 Torrette Ancona, Italy
Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats
Authors: Miyauchi Yosuke , Shikama Hisataka , Takasu Toshiyuki , Okamiya Hideaki , Umeda Masako , Hirasaki Eiko , Ohhata Isao , Nakayama Hidetaka , Nakagawa Shoichi
Published: December 2008

Miyauchi Y, Shikama H, Takasu T, Okamiya H, Umeda M, Hirasaki E, Ohhata I, Nakayama H, Nakagawa S. Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats. Eur J Endocrinol 1996:134:467–73. ISSN 0804–4643

The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K+-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K+-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy.

Hisataka Shikama, Endocrinology and Metabolic Disease Research Laboratory, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305 Japan
Progesterone does not alter sympathetic activity in tissues involved in energy balance
Authors: Puerta Marisa , Venero César , Castro Carmen , Abelenda María
Published: December 2008

Puerta M, Venero C, Castro C, Abelenda M. Progesterone does not alter sympathetic activity in tissues involved in energy balance. Eur J Endocrinol 1996;134:508–12. ISSN 0804–4643

Female rats acclimated to thermoneutrality to avoid cold influences received progesterone by means of subcutaneous implants. They increased their food intake and body weight above the values recorded in control animals. None the less, despite the enhanced food intake, no sign of activation of the sympathetic nervous system was observed, as judged by the unaltered noradrenaline content, half-life and turnover rate in brown adipose tissue, pancreas and heart. This indicates that progesterone increases food intake but prevents non-energy-conservation processes regulated by the sympathetic nervous system from taking place. Thus, it facilitates in two different ways the building up of energy stores. Because overfeeding induced by palatable diets increases the sympathetic tone to the organs studied, it is suggested that the central mechanisms regulating energy balance are probably influenced in a different manner by progesterone than by the sensory properties of palatable diets.

M Puerta, Departamento de Biología Animal II (Fisiología Animal), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, E-28040 Madrid, Spain
Selective macrophage depletion in the liver does not prevent the development of the sick euthyroid syndrome in the mouse
Authors: Boelen Anita , Schiphorst Marianne C Platvoet-ter , van Rooijen Nico , Wiersinga Wilmar M
Published: December 2008

Boelen A, Platvoet-ter Schiphorst MC, van Rooijen N, Wiersinga WM. Selective macrophage depletion in the liver does not prevent the development of the sick euthyroid syndrome in the mouse. Eur J Endocrinol 1996;134:513–8. ISSN 0804–4643

A decreased serum triiodothyronine (T3) level is one of the main characteristics of the sick euthyroid syndrome, caused mainly by a decreased 5′-deiodination of thyroxine (T4) in the liver. Cytokines have been implicated in the pathogenesis of the changes in thyroid hormone metabolism during illness. We therefore investigated the role of cytokines produced by the liver macrophages (Kupffer cells) in the development of the sick euthyroid syndrome, which was induced in mice by a single injection of bacterial endotoxin (lipopolysaccharide) or by 24-h starvation. Experiments were carried out with or without previous selective depletion of liver macrophages by intravenous administration of liposome-encapsulated dichloromethylene diphosphonate. Relative to saline-injected pair-fed controls, the administration of lipopolysaccharide caused a decrease of serum T3 and T4 and liver 5′-deiodinase mRNA. Selective depletion of liver macrophages did not affect these changes. Starvation for 24 h decreased serum T3 and T4, associated with a slight decrease of liver 5′-deiodinase mRNA. There were no differences between macrophage-depleted and non-depleted animals in this respect. In summary, selective depletion of liver macrophages did not affect the decrease in serum T3, T4 or liver 5′-deiodinase mRNA induced by lipopolysaccharide or 24-h starvation in mice. We conclude that cytokines produced by Kupffer cells are not involved in the pathogenesis of the sick euthyroid syndrome in this experimental model.

A Boelen, Department of Endocrinology, F5-171 Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands