bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns
Authors: Papantoniou Nicholas E , Papapetrou Peter D , Antsaklis Aristidis J , Kontoleon Panayotis E , Mesogitis Spyros A , Aravantinos Denis
Published: December 2008

Papantoniou NE, Papapetrou PD, Antsaklis AJ, Kontoleon PE, Mesogitis SA, Aravantinos D. Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns. Eur J Endocrinol 1996;134:437–42. ISSN 0804–4643

Undetectable or extremely low levels of circulating immunoreactive parathyroid hormone (PTH) have been reported in human newborns while PTH bioactivity was high. This prompted the hypothesis that the fetal calcemic hormone might be PTH-related protein. The purpose of this study was to measure circulating immunoreactive PTH-related protein in human fetuses and newborns in order to investigate this hypothesis. Parathyroid hormone-related protein (PTHrP(1–86)) and intact PTH were measured using two-site immunoradiometric assays in plasma obtained by cordocentesis from 23 fetuses (19–33 weeks of gestation), from 17 newborns at term (38–41 weeks), from their mothers and from 22 normal women of reproductive age. Plasma PTHrP was detectable in all but one of the fetuses and newborns and in all the mothers and the controls. The mean level was similar among fetuses (19–33 weeks) (0.43 ± 0.18 pmol/l), newborns (0.48 ±0.12), mothers (0.48 ±0.14) and normal controls (0.46 ± 0.09). Plasma PTH was found to be significantly higher in fetuses at midgestation (1.0 ± 0.99 pmol/l) than in the newborns (0.22 ± 0.21) (p < 0.0025); maternal PTH was significantly higher compared to fetal level at mid-gestation (2.1 ± 1.0, p < 0.01) as well as at term (2.69 ± 1.40, p < 0.001). In the control women PTH was 3.07 ± 1.25 pmol/l. These results showed that plasma amino-terminal PTHrP-(1–86)) is detectable during the second half of human fetal life and its level remains unchanged during this period of time, in contrast to changing levels of fetal plasma PTH. The relatively low PTHrP-(1–86) level that we found in the newborns is not responsible for the high PTH-like bioactivity found by some investigators in cord blood at term.

Peter D Papapetrou, Second Division of Endocrinology, "Alexandra" Hospital, 80 Vas. Sofias & Lourou Streets, Athens 115 28, Greece
Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells
Authors: Babajko Sylvie , Binoux Michel
Published: December 2008

Babajko S, Binoux M. Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells. Eur J Endocrinol 1996;134:474–80. ISSN 0804–4643

Growth in neuroblastoma cells is regulated by insulin-like growth factors (IGFs) whose action is modulated by IGF binding proteins (IGFBPs). In this study, SK-N-SH neuroblastoma cells were shown to produce IGF-II, IGFBP-2, IGFBP-4 and small quantities of IGFBP-6. We have studied the effects of a natural morphogen, retinoic acid (RA), on growth and IGFBP expression in these cells. In all experiments, cells were cultured in serum-free medium and treated with 1 μmol/l RA for 12 h. Cell number increased by almost 50% during the first 24 h after the beginning of treatment. This stimulation was inhibited by 80% or more in the presence of the anti-type 1 IGF receptor antibody α-IR3 and anti-IGF-II antibody. The IGF-II concentrations in the culture media, measured after acidic gel filtration, increased about 1.5-fold and Northern blotting showed a concomitant increase in IGF-II mRNA levels. The mitogenic effect of RA therefore reflects its stimulation of IGF-II production. The availability of IGF-II to the cells may also be enhanced because of the proteolysis of IGFBP-2 to which it is bound. After this initial phase, proliferation ceased despite continued IGF-II production between 24 and 72 h. Both IGFBP-2 and IGFBP-4 production decreased, whereas that of IGFBP-6 increased. These changes appeared both in the protein quantities and in their mRNAs. Insulin-like growth factor binding protein 6 has a strong affinity for IGF-II, 5–10 times that of IGFBP-2 and at least 10 times that of the type 1 IGF receptor, and the arrested proliferation may result, at least in part, from sequestration by IGFBP-6 of the IGF-II secreted.

Sylvie Babajko, INSERM U142, Hôpital Saint Antoine, 184 rue du Faubourg, St Antoine, 75571 Paris Cedex 12, France
Measurement of activin in biological fluids by radioimmunoassay, utilizing dissociating agents to remove the interference of follistatin
Authors: McFarlane James R , Foulds Lynda M , Pisciotta Angelique , Robertson David M , de Kretser David M
Published: December 2008

McFarlane JR, Foulds LM, Pisciotta A, Robertson DM, de Kretser DM. Measurement of activin in biological fluids by radioimmunoassay, utilizing dissociating agents to remove the interference of follistatin. Eur J Endocrinol 1996;134:481–9. ISSN 0804–4643

Activin, a dimer of the β-subunits of inhibin, is a member of the transforming growth factor beta (TGF-β) superfamily of growth factors and has a widespread range of actions in a variety of tissues. The investigation of the physiology of activin action has been facilitated in recent years by the availability of immunoassays in addition to bioassays. Follistatin has been shown to bind to activin with a high affinity and therefore interferes in both radioimmunoassays and enzyme-linked immunosorbent assays (ELISAs). In this study we examined the effect of various surfactants and 1.4-dioxane on the measurement of activin in the presence of follistatin by radioimmunoassay. The addition of a combination of sodium deoxycholate, Tween 20 and sodium dodecyl sulphate removed the interference of follistatin in the radioimmunoassay. The measured content of activin in male rat serum, human male serum, human female serum and bovine follicular fluid rose from 3.29 to 4.15, < 0.48 to 2.87, 2.42 to 4.17 and 30.9 to 85.6 ng/ml, respectively, when assayed in the presence of the dissociating reagents. It was unclear whether the altered potencies were due to a dissociation of the follistatin/activin complex rather than the exposure of the epitope on activin recognized by the antiserum. Serum concentrations of activin were lower than those found in testicular cytosols, and after castration no change in serum activin levels was observed, suggesting that the testis does not contribute significantly to circulating activin levels. The use of the dissociating reagents in the radioimmunoassay will enable studies to be carried out that more accurately measure the activin content of various biological fluids, and thus lead to a greater understanding of the physiology of this growth factor.

James McFarlane, Institute of Reproduction and Development, Level 3, Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia
Expression of endothelin precursor genes in human trophoblast in culture
Authors: Robert Brigitte , Malassiné André , Bourgeois Christelle , Mignot Thérèse-Marie , Cronier Laurent , Ferré Françoise , Duc-Goiran Paulette
Published: December 2008

Robert B, Malassiné A, Bourgeois C, Mignot T-M, Cronier L, Ferré F, Duc-Goiran P. Expression of endothelin precursor genes in human trophoblast in culture. Eur J Endocrinol 1996;134:490–6. ISSN 0804–4643

We have shown previously the presence of immunoreactive endothelin in cultured trophoblastic cells from human term placenta as well as in the trophoblast-conditioned medium. To confirm whether or not the differentiated syncytiotrophoblast is a site for endothelin synthesis, we investigated, by reverse transcription and polymerase chain reaction, the expression of the three preproendothelin genes in 3-day cultured trophoblast. While no endothelin-2 precursor mRNA was detected, preproendothelin-1 mRNA was found to be expressed by the trophoblast. The endothelin-3 precursor gene was also expressed, but at low level and it was detected only after Southern blotting and oligonucleotide hybridization. The ability of trophoblast in culture to express the endothelin precursor genes supports the idea that, in human term placenta, villous syncytiotrophoblast that lines the intervillous space containing maternal blood acts as an endothelial layer.

B Robert, U.361 INSERM, Maternité Baudelocque, 123 Bld de Port-Royal, 75014 Paris, France
Expression of sterol carrier protein 2 (SCP2) in human adrenocortical tissue
Authors: Yanase Toshihiko , Hara Takayuki , Sakai Yoshiyuki , Takayanagi Ryoichi , Nawata Hajime
Published: December 2008

Yanase T, Hara T, Sakai Y, Takayanagi R, Nawata H. Expression of sterol carrier protein 2 (SCP2) in human adrenocortical tissue. Eur J Endocrinol 1996;134:501–7. ISSN 0804–4643

Sterol carrier protein 2 (SCP2) has been implicated in adrenal steroidogenesis by in vitro studies. In order to clarify the clinical significance of SCP2 in human steroidogenesis, we investigated the expression of SCP2 mRNA in various types of adrenocortical tissue and one testis and examined the correlation between the amounts of SCP2 and other values such as the free cholesterol content and the cholesterol side-chain cleavage (SCC) activity in the tissue mitochondria, The types of adrenocortical tissue examined included adrenocortical carcinomas (N = 3), adrenocortical adenomas from patients with Conn's syndrome (N = 3) and from patients with Cushing's syndrome (N = 3), non-functioning adrenocortical adenomas (N = 2) and normal adrenal glands (N = 2). Northern blot hybridization predominantly revealed a 1.8-kb SCP2 mRNA in all tissue specimens examined. The mRNA concentrations of SCP2 in two out of three adrenocortical carcinomas were relatively lower than those in other types of tissue. No other special tendency was observed regarding the mRNA expression levels in various tissue specimens. The mRNA concentrations of SCP2 correlated significantly with mitochondrial contents of free cholesterol (r = 0.67, p < 0.01), but was not correlated with the SCC activities in mitochondria measured by an in vitro enzyme assay. The mitochondrial SCC activities, however, were correlated significantly with the protein levels of mitochondrial P-450 scc determined by a Western blot analysis (r = 0.79, p < 0.01). The significant positive correlation between mRNA concentrations of SCP2 and the mitochondrial content of free cholesterol suggests that the central role of SCP2 in human steroidogenic tissues may be in part a translocation of cytoplasmic free cholesterol to the mitochondria, as demonstrated previously by in vitro studies.

Toshihiko Yanase, Third Department of Internal Medicine, Faculty of Medicine, Maidashi 3-1-1, Higashi-ku, Fukuoka 812, Japan
Luteinizing hormone receptor mutations and sex differentiation
Authors: Themmen Axel PN , Brunner Han G
Published: December 2008

Themmen APN, Brunner HG. Luteinizing hormone receptor mutations and sex differentiation. Eur J Endocrinol 1996;134:533–40. ISSN 0804–4643

Mutations in the luteinizing hormone (LH) receptor gene have been found in patients with abnormalities in their sexual differentiation. In this paper we review results obtained in the studies of these LH receptor mutations. Activating and inactivating mutations are discussed with respect to the mechanism of action of LH/human chorionic gonadotrophin but also in light of their impact of the present knowledge of the physiology of sex differentiation and gonadal function.

APN Themmen, Department of Endocrinology and Reproduction, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands
Analysis of normal and truncated holo- and apo-retinol-binding protein (RBP) in human serum: altered ratios in chronic renal failure
Authors: Jaconi Stefano , Saurat Jean-Hilaire , Siegenthaler Georges
Published: December 2008

Jaconi S, Saurat J-H, Siegenthaler G. Analysis of normal and truncated holo- and apo-retinol-binding protein (RBP) in human serum: altered ratios in chronic renal failure. Eur J Endocrinol 1996;134:576–82. ISSN 0804–4643

Retinol, the precursor of the retinoic acid hormone, is transported in the serum by a specific carrier, the retinol-binding protein (RBP). Compared to serum of healthy controls, the serum of patients with chronic renal failure (CRF) contains markedly increased levels of the RBP form truncated at the C-terminal, des(182Leu-183Leu). (RBP2). which suggests that RBP2 is cleared by the kidney in healthy people but accumulates in serum of CRF patients (Jaconi S, et al. J Lipid Res 1995;36:1247–53). To understand better the mechanism of retinol transport, we have developed a new analytical strategy to analyze the various forms of RBP that circulate in the blood: RBP with and without retinol (holo- and apo-RBP, respectively), RBP bound or not to transthyretin (TTR) and to determine in which of these forms RBP2 circulates. We confirm, but now by direct measurement, that holo-RBP and, to a larger extent, apo-RBP are increased in CRF serum compared to normal serum. We also show that almost all apo-RBP and about 50% of total holo-RBP, corresponding to RBP excess in CRF serum, circulate free and are not complexed to TTR, the remaining 50% being complexed to TTR. This observation suggests that the high levels of free holo-RBP, not bound to TTR, which correspond to the increase in total RBPs measured in CRF serum, may alter the tissue uptake of retinol and be responsible for the signs of hypervitaminosis A observed in these patients. Secondly, we found that the truncation resulting in RBP2 does not alter its binding properties for retinol nor those of holo-RBP2 for TTR. We observed that the high amounts of free holo-RBP2 and holo-RBP in sera of CRF patients were low in normal serum, suggesting that these forms are cleared by the kidney in normal conditions. The possible role of free holo-RBPs is discussed in the context of retinol recycling.

Georges Siegenthaler, Clinique de Dermatologie, Hôpital Cantonal Universitaire, CH-1211 Geneve 14, Switzerland
Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell
Authors: Lindström Per , Sehlin Janove , Frankel Barbara J
Published: December 2008

Lindström P. Sehlin J, Frankel BJ. Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell. Eur J Endocrinol 1996:134:617–25. ISSN 0804–4643

To characterize insulin release and cytoplasmic free Ca2+ [Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-3H]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2, The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4−, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+]i in 85% of the normal (presumably B) cells. In diabetic cells, the [Ca2+]i response was delayed, subnormal and only observed in 23% of the cells. When perchlorate or another Ca2+ channel agonist, 10 μmol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61–67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K+-induced insulin release was decreased in diabetic islets. The K+ -induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2−]i and exocytosis appear defective in the diabetic Chinese hamster B cell.

Per Lindström, Department of Histology and Cell Biology, Umea University, S-901 87 Umea, Sweden
Immunohistochemical localization and immunoblotting of androgen receptor in spinal neurons of male and female rats
Authors: Lumbroso S , Sandillon F , Georget V , Lobaccaro JM , Brinkmann AO , Privat A , Sultan C
Published: December 2008

Lumbroso S. Sandillon F, Georget V. Lobaccaro JM, Brinkmann AO, Privat A, Sultan C. Immunohistochemical localization and immunoblotting of androgen receptor in spinal neurons of male and female rats. Eur J Endocrinol 1996:134;626–32. ISSN 0804–4643

Androgen activity in the central nervous system, as in other tissues, is mediated by the androgen receptor. We performed the precise localization of the androgen receptor in spinal cord of male and female adult rats by immunohistochemistry using polyclonal antibodies. Light microscopy indicated immunoreactivity in the anterior horn with a strong staining in motoneurons, but staining was also observed in the posterior horn. Electron microscopy showed a predominant nuclear immunostaining. A weaker but significant immunoreactive androgen receptor was also noted in the perinuclear/ intracysternal position. Moreover, no differences were found between male and female rats. Immuno-blotting demonstrated that the androgen receptor is expressed in both ventral and dorsal spinal cord, with an apparent molecular mass identical to that noted in other androgen-dependent tissues. The expression of androgen receptor in motoneurons corroborates the role of androgens in motoneuron growth, development and regeneration and underlies the possibility that androgen receptor abnormality leads to the motoneuron degeneration observed in X-linked spinal and bulbar muscular atrophy.

Charles Sultan, Unité BEDR, Hôpital Lapeyronie, 34295 Montpellier, France
Effect of triiodothyronine administration on estrogen receptor contents in peripuberal Sertoli cells
Authors: Panno ML , Sisci D , Salerno M , Lanzino M , Mauro L , Morrone EG , Pezzi V , Palmero S , Fugassa E , Andò S
Published: December 2008

Panno ML, Sisci D, Salerno M, Lanzino M, Mauro L, Morrone EG, Pezzi V, Palmero S. Fugassa E, Andò S. Effect of triiodothyronine administration on estrogen receptor contents in peripuberal Sertoli cells. Eur J Endocrinol 1996:134:633–8. ISSN 0804–4643

The effects of thyroid hormone on androgen metabolism in peripuberal Sertoli cells through the inhibition of estradiol production have been reported previously. It was our intention to investigate further the possible role of thyroid hormone on the interaction between testicular steroids and Sertoli cells by analyzing the effects of triiodothyronine (T3) on estrogen receptor content in 2-, 3- and 4week-old euthyroid rats. Triiodothyronine treatment (3 μg/100 body wt per day) given during the last week prior to sacrifice resulted in reduced testicular growth in 2-week-old animals. Sertoli cells from all groups were cultured initially under basal conditions for the first 24 h and subsequently in the presence of testosterone and/or T3 for the additional 24 h. The in vitro addition of T3 induced a decrease of estrogen receptors (ERs) in 2- and 3-week-old animals that appeared more pronounced especially in the presence of T3 and testosterone. When T3 was tested in vivo we noticed that the decrease of ER content was even greater in all three groups under the in vitro influence of both T3 and testosterone. In 3-week-old animals a simultaneous assay of ERs in both nuclear and cytoplasmic compartments was performed. The ER concentrations in the nucleus were closely related to those of the cytoplasm. The in vivo administration of T3 was responsible for a greater decrease of ERs in the nucleus than in the cytosol. On the basis of these results, and in agreement with our previous data, we speculate that the effect of T3 in the maturational events of Sertoli cells could involve both estradiol production and ER content.

Sebastiano Andò Cattedra di Fisiopatologia Endocrina, Dipartimento di Biologia Cellulare, Università della Calabria, 87030 Arcavacata di Rende, Cosenza, Italy
Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat
Authors: Dijkstra Grietje , de Rooij Dirk G , de Jong Frank H , van den Hurk Robert
Published: December 2008

Dijkstra G, de Rooij DG, de Jong FH, van den Hurk R. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat. Eur J Endocrinol 1996;134:649–54. ISSN 0804–4643

The aim of this study was to examine the effects of prepubertal hypothyroidism on ovarian development in rats. Therefore, from birth up to day 40 postpartum, rats were given 6-propyl-2-thiouracil (PTU) via the drinking water of mothers and pups. At ages ranging from 12 to 40 days, ovarian weights were measured and serum was collected to estimate thyrotrophin (TSH), folliclestimulating hormone (FSH) and inhibin levels. Two hours before sacrifice the animals received an injection of bromodeoxyuridine (BrdU) to estimate the proliferative activity of the follicular granulosa cells. Ovaries were fixed in Carnoy's fluid and follicle counts were performed on sections stained with anti-BrdU and with haematoxylin and eosin. The PTU treatment resulted in increased serum TSH levels, indicative of hypothyroidism, and markedly lower body and ovarian weights, whereas serum FSH and inhibin levels were hardly affected. At day 40, ovaries of PTU-treated animals contained relatively more secondary and less antral follicles, smaller non-atretic antral follicles and more atretic follicles when compared with untreated rats, while corpora lutea were absent. It is concluded that this disturbed folliculogenesis is due to inadequate thyroid hormone supply, which hampers the differentiation and not the proliferation of granulosa cells because diameters of antral follicles were significantly smaller whereas the BrdU-labelling index had not changed.

Robert van den Hurk, Department of Functional Morphology, Faculty of Veterinary Medicine, PO Box 80.157, 3508 TD Utrecht, The Netherlands
Differential responses of femoral and vertebral bones to long-term excessive l-thyroxine administration in adult rats
Authors: Suwanwalaikorn Sompongse , Ongphiphadhanakul Boonsong , Braverman Lewis E , Baran Daniel T
Published: December 2008

Suwanwalaikorn S, Ongphiphadhanakul B, Braverman LE, Baran DT. Differential responses of femoral and vertebral bones to long-term excessive l-thyroxine administration in adult rats. Eur J Endocrinol 1996;134:655–9. ISSN 0804–4643

Recent studies suggest that thyroid-stimulating hormone suppressive doses of thyroid hormone decrease bone mass in humans and growing rats. To determine the long-term effects of excessive l-thyroxine administration on the femur and vertebrae in an adult rat model, 20 male Sprague-Dawley rats (20 weeks old) were randomized into two groups. Group 1 received l-thyroxine (20 μg/100 g body weight ip daily), and group 2 received normal saline ip daily for 20 weeks. Femoral and lumbar vertebral bone mineral density measurements were performed at 0, 6, 15, 18 and 20 weeks of treatment. After 20 weeks of treatment, total RNA was isolated from both femoral and lumbar bones. Northern hybridization was performed with 32P-labeled DNA probes for osteocalcin, osteopontin, alkaline phosphatase and tartrate-resistant acid phosphatase. Significant decreases in bone mineral density in the femur of l-thyroxine-treated rats were observed after 15 weeks (p < 0.03). Lumbar bone mineral density was not affected. Both osteoblast (osteocalcin, osteopontin, alkaline phosphatase) and osteoclast (tartrate-resistant acid phosphatase) gene expression markers were increased significantly in the femoral bone (p < 0.001), but not in the lumbar vertebrae of the l-thyroxine-treated rats. We conclude that long-term administration of excessive doses of l-thyroxine to the adult rat preferentially affects femoral but not vertebral bone. This is manifested by decreased bone mineral density as well as increased gene expression markers for osteoblast and osteoclast activity in the femur.

Daniel T Baran, Department of Orthopedics, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Graves' disease in children and adolescents. Late results of surgical treatment
Authors: Rudberg Claes , Johansson Henry , Åkerström Göran , Tuvemo Torsten , Anders Karlsson F
Published: December 2008

Rudberg C, Johansson H, ÅÅ G, Tuvemo T, Karlsson FA. Graves' disease in children and adolescents. Late results of surgical treatment. Eur J Endocrinol 1996;134:710–5. ISSN0804–4643

All children and adolescents with Graves' disease in the county of Uppsala (catchment area population 250000) treated between 1970 and 1994 were evaluated in a retrospective study. The material comprised 31 patients with a mean age of 11 years (range 4–16), 29 (94%) of whom were girls, and four (13%) of the patients had Down's syndrome. Treatment was primarily conservative and surgery was considered if prolonged medical treatment failed. Lasting remission after antithyroid drug therapy (median 6.5 years; range 4.5–8 years) was noted in 6/31 patients (19%), three (10%) of whom subsequently developed hypothyroidism. Twenty-four of the remaining patients (77%) ultimately underwent subtotal (N=20) or total thyroidectomy (N=4) after experiencing one or more episodes of recurrent hyperthyroidism during medical treatment (median 6 years; range 0.5–11 years). After surgery one patient developed permanent hypocalcemia requiring low-dose vitamin D supplementation. During a postoperative follow-up period of 12.2 years (median: range 1–17 years), there were two cases of recurrent thyrotoxicosis, 1 and 10 years after surgery. The results underline that gender and Down's syndrome are risk factors of juvenile Graves' disease and that the disorder often is difficult to control by long-term medical therapy. In such cases thyroid surgery offers a safe and prompt reversal of the thyrotoxicosis. A proportion of the patients may ultimately develop hypothyroidism, substantiating a need for long-term follow-up of persons afflicted with Graves' disease early in life.

F Anders Karlsson, Department of Medicine, University Hospital, S-751 85 Uppsala. Sweden
Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients
Authors: Yang Inmyung , Park Seungjoon , Ryu Meesook , Woo Jeongtaek , Kim Sungwoon , Kim Jinwoo , Kim Youngseol , Choi Youngkil
Published: December 2008

Yang I, Park S, Ryu M, Woo J, Kim S, Kim J, Kim Y, Choi Y. Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients. Eur J Endocrinol 1996;134: 720–6. ISSN 0804–4643

A subset of human growth hormone (GH)-secreting pituitary tumors contains the gsp oncogene that encodes an activation mutation of the α-subunit of the stimulatory GTP-binding protein (Gsα). This study was undertaken to investigate the frequency of the gsp oncogene in GH-secreting pituitary tumors in Korean acromegalic patients and to elucidate the clinical characteristics of these patients to endocrine testing. Direct polymerase chain reaction sequencing revealed the gsp oncogene mutation in 9 out of 21 tumors (43%) at amino acid 201 of the Gsα protein. A single nucleotide mutation in the tumors carrying the gsp oncogene was observed, which replaced an arginine (CGT) in the normal protein with cysteine (TGT) in eight tumors and serine (AGT) in one tumor. The patients with the gsp oncogene mutation (group 1) were older (54 ± 10 vs 41 ±11 years, p = 0.0085) than those without the mutation (group 2). Sex, tumor size and grade, basal GH and prolactin levels, the GH response to oral glucose loading, the GH fluctuation and the paradoxical response to thyrotropin-releasing hormone or gonadotropin-releasing hormone did not differ between the groups. The gsp oncogene was found mostly in somatotroph adenomas. The octreotide-induced GH suppression was significantly higher in group 1 than in group 2 (95 ± 5% vs 81 ± 17%, p = 0.0335). The GH response to bromocriptine did not differ between the groups. These results suggest that the Gsα mutations of GH-secreting tumor are observed in Korean acromegalic patients with similar frequency to those of western countries. The patients with gsp oncogene are likely to be older than those without the oncogene, and show excellent response of GH suppression to octreotide.

Inmyung Yang, Division of Endocrinology, Department of Internal Medicine, Kyunghee University School of Medicine, 1 Hoiki-dong, Dongdaemoon-ku, Seoul 130-702, Korea
Pituitary insufficiency and regression of acromegaly caused by pituitary apoplexy following cerebral angiography
Authors: Louwerens Marloes , de Herder Wouter W , Postema Pieter TE , Tanghe Hervé LJ , Lamberts Steven WJ
Published: December 2008

Louwerens M, de Herder WW, Postema PTE, Tanghe HLJ, Lamberts SWJ. Pituitary insufficiency and regression of acromegaly caused by pituitary apoplexy following cerebral angiography. Eur J Endocrinol 1996;134:737–40. ISSN 0804–4643

Pituitary apoplexy as a complication of cerebral angiography has been described in only a few case reports. Some studies have reported the clinical resolution of active acromegaly after pituitary apoplexy. We present a patient with active acromegaly due to a growth hormone (GH)-secreting pituitary macroadenoma, who developed anterior and posterior pituitary insufficiency following cerebral angiography. Furthermore, a significant reduction in tumour size was accompanied by normalization of mean 24 h in GH insulin-like growth factor I (IGF-I) and IGF binding protein 3 levels.

WW de Herder, Department of Internal Medicine III and Clinical Endocrinology, University Hospital Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Permissive role of α-tocopherol in the stimulation of aldosterone by sodium depletion in the guinea pig
Authors: Möbius K , Redmann A , Hiller HH , Oelkers W , Bähr V
Published: December 2008

Möbius K, Redmann A, Hiller HH, Oelkers W, Bähr V. Permissive role of α-tocopherol in the stimulation of aldosterone by sodium depletion in the guinea pig. Eur J Endocrinol 1996;134:758–63. ISSN 0804–4643

To investigate the role of vitamin E in aldosterone synthesis, in vivo and in vitro studies were done in α-tocopherol-depleted guinea pigs. Seventy-one days of low vitamin E intake (< 5 mg/kg feed) reduced the concentration of α-tocopherol in serum, liver and adrenals to low levels with no signs of hypovitaminosis. Aldosterone secretion was stimulated by 15 days on a low sodium diet (200 mg/kg feed) in controls and vitamin E-depleted animals. Sodium depletion in controls stimulated plasma aldosterone by 335%. Vitamin E depletion reduced the stimulation of plasma aldosterone to only 112% (p < 0.05). In vitro aldosterone secretion by adrenal cells from sodium-depleted animals was 252% higher than secretion by cells from controls. This enhancement of in vitro aldosterone secretion following in vivo sodium depletion was abolished completely by combined in vivo vitamin E and sodium depletion (p < 0.05). No significant differences between groups were found for plasma renin activity, adrenocorticotrophin and serum potassium, suggesting that intra-adrenal mechanisms like damage by enhanced lipid peroxidation in α-tocopherol-depleted animals rather than changes in humoral aldosterone-regulating factors are the cause of the attenuated aldosterone response to sodium depletion.

Volker Bähr, Abteilung Endokrinologie, Medizinische Klinik, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12000 Berlin, Germany
Coordinate expression of insulin-like growth factor II (IGF-II) and IGF-II/mannose-6-phosphate receptor mRNA and stable expression of IGF-I receptor mRNA during differentiation of human colon carcinoma cells (Caco-2)
Authors: Hoeflich Andreas , Yang Yi , Rascher Wolfgang , Blum Werner F , Huber Stefan , Koepf Gabriele , Kolb Helmut J , Kiess Wieland
Published: December 2008

Hoeflich A, Yang Y, Rascher W, Blum WF, Huber S, Koepf G, Kolb HJ, Kiess W. Coordinate expression of insulin-like growth factor II (IGF-II) and IGF-II/mannose-6-phosphate receptor mRNA and stable expression of IGF-I receptor mRNA during differentiation of human colon carcinoma cells (Caco-2). Eur J Endocrinol 1996;135:49–59. ISSN 0804–4643

Insulin-like growth factor II (IGF-II) has been implicated in the differentiation of skeletal muscle cells. In this study the putative role of IGF-II in epithelial cell differentiation was investigated. The expression of IGF-II, IGF-1 receptor and IGF-II/mannose-6-phosphate receptor (IGF-II/M6P receptor) mRNA during spontaneous differentiation of the colon carcinoma cell line Caco-2 was measured. In addition, differentiation of Caco-2 cells during the cell culture period (days 1–21 in culture) was studied in parallel using morphological (light and scanning electron microscopy) and biochemical markers of growth (DNA, RNA and protein content, and β-actin mRNA and glyceraldehyde phosphate dehydrogenase mRNA expression) and differentiation (alkaline phosphatase activity, carcinoembryonic antigen content). A putative correlation between the markers of growth and differentiation and IGF gene expression was studied using linear regression analysis. Expression of IGF-II mRNA and IGF-II/M6P receptor mRNA correlated significantly with the progress of differentiation, while the IGF-I receptor was stably expressed throughout the culture period and exhibited a crucial role for the survival of Caco-2 cells, as shown by blocking experiments employing the monoclonal anti-IGF-I receptor antibody alpha-IR3. We hypothesize that: IGF-II mRNA and IGF-II/M6P receptor mRNA are expressed in a coordinate fashion during the differentiation of Caco-2 cells; coordinate expression of IGF-II and of IGF-II/M6P receptor mRNA might point to a role for IGF-II as a growth stimulant and for the IGF-II/M6P receptor for a regulator of IGF-II bioavailability in differentiating cells; alternatively, high IGF-II/M6P receptor mRNA and protein expression in differentiated cells but low IGF-II binding to the IGF-II/M6P receptor point to an important intracellular role of this receptor type in differentiated colon epithelial cells; the IGF-I receptor mRNA is stably expressed during the differentiation process of Caco-2 cells; the IGF-I receptor protein seems to be a prerequisite for the survival of Caco-2 cells.

W Kiess, Children's Hospital, Justus Liebig University, Feulgenstr. 12, D-35385 Giessen, Germany
Fracture rate, pre- and postmenopausal bone mass and early and late postmenopausal bone loss are not associated with vitamin D receptor genotype in a high-endemic area of osteoporosis
Authors: Berg Jens P , Falch Jan A , Haug Egil
Published: December 2008

Berg JP, Falch JA, Haug E, Fracture rate, pre- and postmenopausal bone mass and early and late postmenopausal bone loss are not associated with vitamin D receptor genotype in a high-endemic area of osteoporosis. Eur J Endocrinol 1996;135:96–100. ISSN 0804–4643

To investigate a possible association between vitamin D receptor genotype and development of postmenopausal osteoporosis, a longitudinal study from 1977 to 1995 was carried out on women living in Oslo, Norway. One hundred and eighteen premenopausal women born in 1930 were included in a study of pre- and postmenopausal bone loss in 1977. In 1995, blood samples for vitamin D receptor genotyping were available in 72, 42 and 49 of the women eligible for the determination of premenopausal bone mineral content, early postmenopausal appendicular bone loss and late postmenopausal bone mineral content, bone loss and fractures, respectively. Bone mineral density was measured in the distal and proximal right forearm annually from 1977 to 1987, and in the lumbar spine, proximal femur, right forearm and total body, including ultrasound measurements of the right calcaneus, in 1993 and 1995. Non-spinal fractures were also recorded. The results were compared to the individual vitamin D receptor genotype and it was found that vitamin D receptor genotype was neither associated with non-spinal fractures, pre- and postmenopausal bone mass nor with early and late postmenopausal bone loss within the age of 65 years. In conclusion, premenopausal bone mass, postmenopausal bone loss and the subsequent risk of osteoporosis and fractures were not predicted by vitamin D receptor genotype in a high-endemic area of osteoporosis.

Jens P Berg, Hormone Laboratory, Aker University Hospital, Trondheimsveien 235, N-0514 Oslo, Norway
Effects of insulin-like growth factor I on growth, epithelial barrier and iodide transport in polarized pig thyrocyte monolayers
Authors: Ericson Lars E , Nilsson Mikael
Published: December 2008

Ericson LE, Nilsson M. Effects of insulin-like growth factor I on growth, epithelial barrier and iodide transport in polarized pig thyrocyte monolayers. Eur J Endocrinol 1996;135:118–27. ISSN 0804–4643

The effects of insulin-like growth factor I (IGF-I) on mitogenesis, epithelial barrier function and transepithelial iodide transport were studied in confluent, polarized monolayers of pig thyrocytes cultured on filter in Transwell bicameral chambers. The growth rate in controls cultured in 1% fetal calf serum was low. Insulin-like growth factor I stimulated dose-dependently the incorporation of [3H]thymidine, maximally at 100 ng/ml, which corresponded to an increase of DNA content by 60% after 6 days. Thyrotropin (1 mU/ml) alone did not stimulate cell multiplication but inhibited partially the stimulatory effect of IGF-I. Insulin-like growth factor I(100 ng/ml) increased within 10 min the transepithelial potential difference, which remained elevated for several days, but did not significantly change the transepithelial resistance. When added together, IGF-I reinforced the effects of TSH on potential difference (increase) and resistance (decrease). A preserved epithelial barrier in IGF-I-treated cultures was confirmed by observing a normal immunolocalization of the tight junction protein ZO-1 and an unchanged ultrastructure of the junctional complex. Insulin-like growth factor I increased the transepithelial flux of 125I− in the basal-to-apical, but not in the opposite, direction. Stimulation of iodide transport by IGF-I was modest after 2 days and pronounced after 6 days. In comparison, TSH-stimulated iodide transport was higher after 2 days but lower after 6 days. Both TSH and IGF-I were strongly synergistic, after 6 days amounting to a 90-fold increase over the control basoapical 125I− transfer. The simultaneous accumulation of 125I− in the cell layer was increased two- to fourfold by IGF-I and/or TSH. In conclusion, IGF-I is able to induce growth in preformed monolayers of pig thyrocytes cultured on permeable filter. During these conditions, the mitogenic effect of IGF-I is partially inhibited by TSH, which has no growth-promoting action on its own. The transepithelial transport of iodide and bulk electrolytes is altered by IGF-I without affecting the epithelial barrier function. Specifically, IGF-I up-regulates the activity of the basolateral iodide pump and increases the iodide permeability of the apical plasma membrane. The action of IGF-I on iodide transport is independent of, although synergistic with, that of TSH. The findings support the notion that IGF-I may be an important regulator of thyroid growth and differentiated functions.

Lars E Ericson, Institute of Anatomy and Cell Biology, Göteborg University, Medicinaregatan 3, S-413 90 Göteborg, Sweden
Melatonin receptors in the chicken kidney are up-regulated by pinealectomy and linked to adenylate cyclase
Authors: Song Y , Pang CS , Ayre EA , Brown GM , Pang SF
Published: December 2008

Song Y, Pang CS, Ayre EA, Brown GM, Pang SF. Melatonin receptors in the chicken kidney are upregulated by pinealectomy and linked to adenylate cyclase. Eur J Endocrinol 1996;135:128–33. ISSN 0804–4643

The effect of pinealectomy on the characteristics of melatonin receptors in the chicken kidney was studied. One-day-old chicks were operated and kept under a 12 h/12 h light/dark photoperiod. Six weeks after operation, the animals were sacrificed at mid-light and mid-dark. Serum melatonin was determined by radioimmunoassay and kidney melatonin receptors were studied by radioreceptor assay using the melatonin agonist 2-[125I]iodomelatonin as the radioligand. Pinealectomy significantly reduced the mid-dark serum melatonin level and abolished the diurnal rhythm of 2-[125I]iodomelatonin binding in the kidney. The density of 2-[125I]Iodomelatonin binding sites in the kidney at mid-dark was increased significantly to a value comparable to the mid-light density after pineal ablation. Our results suggest that melatonin receptors in the chicken kidney are directly regulated by melatonin in the circulation. The coupling of kidney melatonin receptors to adenylate cyclase was investigated. The basal and forskolin-stimulated cAMP production in chicken kidney explants was studied following melatonin or melatonin plus pertussis toxin treatment. Levels of cAMP in chicken kidney explants were extracted and determined by radioimmunoassay. Melatonin had no effect on basal cAMP levels. However, melatonin significantly inhibited the forskolin-stimulated cAMP accumulation at a concentration of 10 pmol/l. Inhibitory effects of melatonin on the forskolin-stimulated cAMP increase in the chicken kidney were totally blocked by preincubating the kidney tissue with 1.0 μg/ml pertussis toxin. Our results suggest that kidney melatonin receptors may modulate the adenylate cyclase leading to biological responses in the renal system.

SF Pang, Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong
Neuroendocrine regulation of pituitary–adrenal function during fetal life
Authors: Brooks AN , Hagan DM , Howe DC
Published: December 2008

Brooks AN, Hagan DM, Howe DC. Neuroendocrine regulation of pituitary–adrenal function during fetal life. Eur J Endocrinol 1996;135:153–65. ISSN 0804–4643

During late gestation there is a rise in the concentration of corticosteroids in the fetal circulation that is essential for the coordinated maturation of many fetal organ systems and is a key component in the endocrine pathway leading to the onset of birth. Fetal plasma concentrations of adrenocorticotrophin (ACTH) increase during late, gestation and this rise precedes the increase in plasma corticosteroids. Paradoxically, ACTH and cortisol concentrations increase concomitantly even though cortisol would normally be expected to exert negative feedback effects to inhibit pituitary ACTH secretion. Elucidating the neuroendocrine signals that cause the increase in fetal ACTH, despite the elevated concentrations of cortisol at this time, will therefore provide vital clues as to the trigger for fetal organ maturation and birth. This article describes the normal ontogeny of the hypothalamo–pituitary–adrenal axis, discusses the neuroendocrine signals that trigger the increase in fetal ACTH secretion and provides potential explanations for the concomitant rise in ACTH and cortisol.

AN Brooks, MRC Reproductive Biology Unit, 37 Chalmers Street, Edinburgh, EH3 9EW, Scotland, UK
Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2—relevance of specific mutations in the RET proto-oncogene
Authors: Frank-Raue Karin , Kratt Thomas , Höppner Wolfgang , Buhr Heinz , Ziegler Reinhard , Raue Friedhelm
Published: December 2008

Frank-Raue K, Kratt T, Höppner W, Buhr H, Ziegler R, Raue F. Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2—relevance of specific mutations in the RET proto-oncogene. Eur J Endocrinol 1996;135:222–5. ISSN 0804–4643

It has been suggested that specific mutations in the RET proto-oncogene correlate with clinical manifestation of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. We retrospectively analyzed 61 patients with MEN 2, 28 with associated pheochromocytoma, regarding the relevance of specific mutations in the RET proto-oncogene and the diagnostic sensitivity of catecholamine screening and localization procedures. The present study shows that the position of the RET mutation is related to disease phenotype; codon 634 mutations are predictive of families predisposed to pheochromocytoma. In 18% of our patients, the diagnosis of pheochromocytoma preceded detection of medullary thyroid carcinoma. Therefore, mutation analysis of the RET gene should be performed in apparently "sporadic" cases of pheochromocytoma to confirm or exclude MEN 2. The most sensitive biochemical marker for pheochromocytoma in MEN 2 is 24-h urinary epinephrine excretion. Computed tomography, magnetic resonance imaging and MIBG scintigraphy are all highly sensitive methods to localize pheochromocytoma. We conclude that, in all families with MEN 2, mutational analysis of the RET proto-oncogene should be performed, both to identify gene carriers for MEN 2 and to identify specific mutations that are more strongly associated with pheochromocytoma.

Karin Frank-Raue, Department of Internal Medicine, Endocrinology & Metabolism, Bergheimer Straße 58, 69115 Heidelberg, Germany
Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function
Authors: Sydow Karin , Emrich Dieter , Gefeller Olaf , Schreivogel Inge
Published: December 2008

Sydow K, Emrich D, Gefeller O, Schreivogel I. Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function. Eur J Endocrinol 1996;135:316–21. ISSN 0804–4643

Using sufficiently sensitive and precise assays, we systematically investigated the correlation between thyrotropin, thyroglobulin, index of free thyroxine and index of free triiodothyronine after different doses of thyroxine (25, 50, 100, 150 μg), which were administered daily for 10 days to individuals with normal thyroid function and in a control group. Analysis of the data using relative median values expressing changes to basal values before administration of thyroxine yielded the following results: (i) thyrotropin and thyroglobulin decreased monoexponentially, depending on the doses of thyroxine administered; (ii) the extent of their decrease showed a linear correlation with the dose of thyroxine administered and was greater for thyrotropin than for thyroglobulin; (iii) the relative velocity of their decrease increased monoexponentially with the dose of thyroxine and did not differ between thyrotropin and thyroglobulin. These results provide strong evidence for a clear quantitative reaction of the feedback mechanism and confirm that the secretion of thyroglobulin is a physiological process dependent on thyrotropin. The high intra-individual variations obtained for thyrotropin were probably due to its pulsatile secretion.

D. Emrich, Department of Nuclear Medicine, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany