bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretation of growth hormone provocative tests: comparison of cut-off values in four European laboratories
Authors: Andersson Anna-Maria , Ørskov Hans , Ranke Michael B , Shalet Steve , Skakkebæk Niels E 
Published: December 2008

Andersson A-M, Ørskov H, Ranke MB, Shalet B, Skakkebæk NE. Interpretation of growth hormone provocative tests: comparison of cut-off values in four European laboratories. Eur J Endocrinol 1995;132:340–3. ISSN 0804–4643
To compare interpretations of growth hormone (GH) provocative tests in laboratories using six different GH immunoassays (one enzymeimmunometric assay (EIMA, assay 1), one immunoradiometric assay (IRMA, assay 5), one time-resolved fluorimmunometric assay (TRFIA, assay 3) and three radioimmunoassays (RIAs, assays 2, 4 and 6)), aliquots of peak samples from GH provocative tests were distributed between the four participating laboratories, quantified in the respective immunoassays and interpreted according to the cut-off values for provocative tests defined for each assay method. There was a high degree of relative correlation between the different assays, but absolute GH estimates differed. Assays 2, 4, 5 and 6 yielded almost identical GH levels. Assays 1 and 3 yielded serum GH levels approximately 39% and 70%, respectively, of those of assays 2, 4, 5 and 6. Although the absolute GH level measured in the various assay methods varied, there was good agreement between the interpretation of a given sample among the participating laboratories. This indicates that the differences in estimates of serum GH concentration by different immunoassay systems can be compensated for when cut-off values are defined for each method.
Anna-Maria Andersson, Dept. of Growth and Reproduction, University Hospital of Copenhagen, Ward GR5064, 9 Blegdamsvej, DK-2100 Copenhagen Ø, Denmark
Antibodies against restricted sequences in human c-ErbA hinge domain recognize differentially natural mammalian α- or β-type triiodothyronine receptors and interfere differently with hormone binding
Authors: Bismuth Janine , Lenoir Christelle , Teboul Michèle , Daadi Malika , Giorgilli Gianfranco , Bonne Jeannine , Macchia Enrico , Planells Richard , Torresani Janine 
Published: December 2008

Bismuth J, Lenoir C, Teboul M, Daadi M, Giorgilli G, Bonne J, Macchia E, Planells R, Torresani J. Antibodies against restricted sequences in human c-ErbA hinge domain recognize differentially natural mammalian α- or β-type triiodothyronine receptors and interfere differently with hormone binding. Eur J Endocrinol 1995;132:347–56. ISSN 0804–4643
In our first report, rabbit antibodies directed to recombinant polypeptides of human α-type c-ErbA sequences recognized natural triiodothyronine (T3) receptors (TR) in adipocytes (mouse Ob 17 cell line) but not in liver (mouse, rat). Moreover, some of them, directed to the sequence 150–228, markedly interfered with hormone binding to adipocyte T3 receptors. We now raised antibodies against shorter synthetic peptides within this α-type 150–228 c-ErbA sequence, which encompasses part of the hinge (D) domain and N-terminus of the E domain (α-150–166 and α 172–191) and against a β-type c-ErbA sequence (β 204–220 aligned on α 150–166, and differing by eight amino acids). Our present antibodies, which bear the expected c-ErbA α- or β-type specificity, immunoprecipitated the TR in nuclear extracts, with a different pattern between tissues: exclusive precipitation by anti-c-ErbA α antibodies in Ob 17 adipocytes; large but non-exclusive precipitation by anti-cErbA β antibodies in rat or mouse liver, which also expresses some α-type TR. This pattern of discriminative immunoprecipitation, also obtained in parallel analysis using our previously described antibodies to other c-ErbA α or β sequences (anti-α 144–162, anti-α1 403–410 and anti-β 62–82), roughly verifies results of c-erbA mRNA expression in these tissues. Slight differences appeared in the extent of α-type TR recognition by antibodies directed to α 172–191, whether TR were liganded or not to T3 before antibody addition. This evokes a different conformation of this region after hormone binding. Most interestingly, these anti-α 172–191 antibodies lowered the Ka for T3 and extensively dissociated the adipocyte T3–TR complexes; they interfered poorly with the binding of T3 in liver nuclear extracts. This strongly supports the concept that internal sequences in c-ErbA α, more precisely in a restricted Cterminal part of the D domain, are necessary for efficient T3 binding, which also need the C-terminal part of domain E.
J. Torresani, INSERM U38, Biochimie Méducake, Faculté de Médecine, 27 Bd J Moulin, 13385 Marseille Cédex 5, France
Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone antagonist-treated male rats
Authors: Tena-Sempere M , Pinilla L , Aguilar E 
Published: December 2008

Tena-Sempere M, Pinilla L, Aguilar E. Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone agonist-treated male rats. Eur J Endocrinol 1995;132: 357–62. ISSN 0804–4643
The pituitary component of the feedback mechanisms exerted by testicular factors on gonadotropin secretion was analyzed in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. In order to discriminate between androgens and testicular peptides, groups of males were orchidectomized (to eliminate androgens and non-androgenic testicular factors) or injected with ethylene dimethane sulfonate (EDS), a selective toxin for Leydig cells (to eliminate selectively androgens) and treated for 15 days with vehicle or the GnRH antagonist Ac-d-pClPhe-d-pClPhe-d-TrpSer-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Org.30276, 5 mg/kg/72 hours). Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured 7 and 14 days after the beginning of treatment. We found that: in males treated with GnRH antagonist, orchidectomy or EDS treatment did not induce any increase in LH secretion; and orchidectomy, but not EDS treatment, increased FSH secretion in GnRH-treated males. The present results show that negative feedback of testicular factors on LH secretion is mediated completely through changes in GnRH actions. In contrast, a part of the inhibitory action of the testis on FSH secretion is exerted directly at the pituitary level. It can be hypothesized that non-Leydig cell testicular factor(s) inputs at different levels of the hypothalamic–pituitary axis in controlling LH and FSH secretion.
Manuel Tena-Sempere, Department of Physiology, Faculty of Medicine, University of Córdoba, 14004 Córdoba, Spain
Differences in insulin secretion between the rat and mouse: role of cAMP
Authors: Ma Yan Hui , Wang Jian , Rodd Gail G , Bolaffi Janice L , Grodsky Gerold M 
Published: December 2008

Ma YH, Wang J, Rodd GG, Bolaffi JL, Grodsky GM. Differences in insulin secretion between the rat and mouse: role of cAMP. Eur J Endocrinol 1995;132:370–6. ISSN 0804–4643
Although information regarding insulin secretion usually is considered equivalent when generated in the mouse or the rat, it is established that the kinetics of insulin secretion from mouse and rat pancreatic beta cells differ. The mechanisms underlining these differences are not understood. The in vitro perfused pancreas and isolated islets of the mouse or rat were employed in this study to investigate the role of cyclic adenosine monophosphate (cAMP), a major positive modulator of betacell function, as one differentiating signal for the uniquely different insulin release from the beta cells of these commonly used rodents. Glucose-stimulated first-phase insulin release from the perfused pancreas of the rat was higher than the mouse when calculated per gram of pancreas or as fractional secretion, but this phase was identical in the two species when results were adjusted for total body weight. Whether related to insulin content, pancreatic weight or body weight, the rat pancreas responded to glucose with a progressively increasing second-phase insulin release compared to the mouse pancreas, which secreted a flat second-phase of lesser magnitude. Isolated islets from rat and mouse were comparable in insulin content whereas the basal cAMP level of mouse islets was less than half that of the rat. At submaximal stimulation with glucose or glucose + IBMX or forskolin, mouse islets exhibited lower cAMP levels to a given stimulus than the rat. In rat islets cAMP levels increased to approximately 1000 fmol per islet, although insulin secretion maximized by 100–150 fmol. Insulin release at the same 100–150fmol cAMP per mouse islet was one-third that of the rat and secretion had not maximized in mouse islets at 800 fmol. Despite their similar insulin contents, mouse islets consistently secreted less insulin for a given level of cAMP per islet than the rat. The lower capacity of mouse islets to achieve comparable cAMP levels was not the result of increased catabolic rate because the "half-time" disappearance of islet cAMP after a stimulus was similar (~1 min) for both species. It is concluded that, compared to the mouse, beta cells of the rat pancreas elicit a more pronounced secondphase insulin secretion that is due, at least in part, to a greater production of, and sensitivity to, cAMP.
Gerold M Grodsky, Metabolic Research Unit, University of California, H5W 1157, Box 0540, 3rd and Parnassus Avenue, San Francisco, CA 94143, USA
Identification of the thyroid Na+/I− cotransporter as a potential autoantigen in thyroid autoimmune disease
Authors: Raspé E , Costagliola S , Ruf J , Mariotti S , Dumont JE , Ludgate M 
Published: December 2008

Raspé E, Costagliola S, Ruf J, Mariotti S, Dumont JE, Ludgate M. Identification of the thyroid Na+/I− cotransporter as a potential autoantigen in thyroid autoimmune disease. Eur J Endocrinol 1995;132: 399–405. ISSN 0804–4643
The thyroid gland is the target of several autoimmune diseases. Specific thyroid proteins have been identified as autoantigens associated with these diseases (e.g. thyroperoxidase, thyroglobulin and the thyrotrophin (TSH) receptor). In this paper, we report that the serum of a patient suffering from Hashimoto's thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit the chronic TSH-induced I− uptake of dog thyrocytes in culture, even at a 1:1000-fold dilution, without affecting their 86Rb+ uptake. This blocking activity is rare as 147 sera (from patients positive for antibodies to the thyroid microsomes and the gastric parietal cell antigen, patients with Sjögren's syndrome, patients with a high titre of microsomal antibodies and low or negative for antibodies to thyroperoxidase, and patients with a high titre of microsomal antibodies and frank hypothyroidism) were negative when tested for their ability to inhibit I− uptake. Subsequently we tested 20 murine monoclonal antibodies previously obtained by immunizing mice with a crude human thyroid membrane preparation, which were all negative when tested against thyroglobulin and thyroperoxidase. One of the monoclonal antibodies displayed a 50% inhibition of the chronic TSH-induced 125I− uptake of dog thyrocytes without affecting the 86Rb+ uptake of the cells. Immunoglobulins purified from the ascite fluid by affinity chromatography on a protein A cellulose column had the same characteristics. Taken together, the data suggest that thyroidal 125I− uptake can be inhibited by antibodies, that autoantibodies in the patient's serum are most probably responsible for the observed inhibition and therefore that the Na+/I− cotransporter is probably an autoantigen.
E Raspé, IRIBHN, School of Medicine, Free University of Brussels (ULB), 808 route de Lennik, 1070 Bruxelles, Belgium
Four years' treatment of resistant acromegaly with octreotide
Authors: Mcknight John A , McCance David R , Sheridan Brian , Atkinson A Brew 
Published: December 2008

McKnight JA, McCance, DR, Sheridan B, Atkinson AB. Four years' treatment of resistant acromegaly with octreotide. Eur J Endocrinol 1995;132:429–32. ISSN 0804–4643
This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21–62 years) with persistent growth hormone (GH) elevation (duration 1–15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 μg three times daily. The dose then was reduced to 200 μg three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (± sem) was 36.0 ± 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 ± 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3–9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4–15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect. Two hours after glucose load the plasma glucose level was elevated but HbA1 did not change long term. Further similar studies of long duration are required to establish the long-term safety profile of the drug.
AB Atkinson, Sir George E Clark Metabolic Unit, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland
Quantification of urinary insulin-like growth factors (IGFs) and IGF binding protein 3 in healthy volunteers before and after stimulation with recombinant human growth hormone
Authors: Tönshoff Burkhard , Blum Werner F , Vickers Mark , Kurilenko Sabine , Mehls Otto , Ritz Eberhard 
Published: December 2008

Tönshoff B, Blum WF, Vickers M, Kurilenko S, Mehls 0, Ritz E. Quantification of urinary insulin-like growth factors (IGFs) and IGF binding protein 3 in healthy volunteers before and after stimulation with recombinant human growth hormone. Eur J Endocrinol 1995;132:433–7. ISSN 0804–4643
We examined excretion of urinary insulin-like growth factors I and II (IGF-I and IGF-II) and their major binding protein IGFBP-3 in comparison to their respective serum concentration in nine healthy female volunteers (median age 25 years, range 22–27) under baseline conditions and after stimulation with recombinant human growth hormone (rhGH), 4.5 IU twice daily subcutaneously for a period of 3 days. The IGFs were measured in unconcentrated urine by use of recently developed, highly sensitive radioimmunoassays. The IGFBP-3 was measured by a specific radioimmunoassay. The mean (±sd) urinary concentrations of IGF-I (0.08 ± 0.07 μg/l), IGF-II (1.02 ± 0.47 μg/l) and IGFBP-3 (19.1 ± 6.9 μg/l) were two to three orders of magnitude lower than in serum. The ratio of IGF-II over IGF-I concentration in urine (13:1) was five times higher than in serum (2.5:1), and the ratio of IGFBP-3 over the sum of IGF-I and IGF-II in urine (17:1) was four times higher than in serum (4:1). Urinary excretion was 63.3 ± 46.6 ng·m−2 · 24 h−1 for IGF-I, 1002 ± 598 ng·m−2 · 24 h−1 for IGFII and 18039 ± 4983 ng·m−2·24 h−1 for IGFBP-3. Using fast protein liquid exclusion chromatography, only immunoreactive IGFBP-3 components of less than 60 kD were detected in urine, with a major peak at 20kD. Urinary IGFBP-3 excretion correlated with serum IGFBP-3 (r = 0.61, p < 0.01) and the glomerular filtration rate (r = 0.56, p < 0.05) measured by steady-state inulin infusion clearances. Administration of rhGH stimulated significantly (p < 0.005) the serum IGF-I concentration by 50%, but not the urinary IGF-I excretion. In conclusion: the considerably higher ratio of IGF-II to IGF-I in urine compared to serum indicates that urinary IGF excretion does not represent only filtered IGFs, urinary IGF-I is a less sensitive indicator of GH activity than serum IGF-I, and as urinary IGFBP-3 excretion is in proportion to the glomerular filtration rate and serum IGFBP-3, it presumably reflects renal filtration of small immunoreactive IGFBP-3 fragments from the circulation.
Burkhard Tönshoff, University Children's Hospital, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
Midmolecular parathyroid hormone-related peptide in serum during pregnancy, lactation and in umbilical cord blood
Authors: Bucht Elisabet , Rong Haiqin , Bremme Katarina , Granberg Barbro , Rian Edith , Tørring Ove 
Published: December 2008

Bucht E, Rong H, Bremme K, Granberg B, Rian E, Tørring 0. Midmolecular parathyroid hormonerelated peptide in serum during pregnancy, lactation and in umbilical cord blood. Eur J Endocrinol 1993;132:438–43. ISSN 0804–4643
Indications of an important physiological role of parathyroid hormone-related peptide (PTHrP) for fetal calcium homeostasis, maternal–fetal calcium transport and reproduction have accumulated over recent years. The PTHrP concentrations were measured by an earlier developed midregion radioimmunoassay in serum from lactating healthy females and umbilical cord blood and compared with levels in age-matched non-pregnant or lactating females. The PTHrP concentrations could be measured in all samples after silica cartridge C18 extraction of 10–12 ml of serum. The concentrations were significantly higher during lactation (mean ± sd: 0.72 ± 0.14 pmol/l, N = 22) and in umbilical cord blood (0.85 ± 0.18 pmol/l, N =12) compared with healthy age-matched women (0.48 ± 0.09 pmol/l, N = 10, p< 0.001). The molecular forms of PTHrP were also studied in an agematched control group, in pregnant women and in umbilical cord blood by gel chromatography in a fast protein liquid chromatography system of Sep-Pak-extracted pooled serum. In all three groups we found heterogeneity of the molecular forms with two predominant peaks. The smallest fragment had a molecular weight of 4–6 kD while the largest form appeared as a high-molecular-weight molecule. In conclusion, the concentrations of midmolecule PTHrP fragments in serum are elevated during lactation and in umbilical cord blood. Because the midregion of PTHrP has unique actions, our results indicate that PTHrP may play an important physiological role for the mother and for the maternal–fetal calcium transport.
Elisabet Bucht, Department of Molecular Medicine, Unit of Endocrinology and Diabetology, Karolinska Hospital, S-171 76 Stockholm, Sweden
Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis
Authors: Bell Helge , Raknerud Nils , Falch Jan A , Haug Egil 
Published: December 2008

Bell H, Raknerud N, Falch JA, Haug E. Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis. Eur J Endocrinol 1995;132:444–9. ISSN 0804–4643
We investigated a group of 111 amenorrhoeic females with associated liver disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other chronic liver diseases (N = 40) admitted to our medical department from 1986 to 1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and prolactin were measured. Serum LH was decreased below the normal range in 50% of patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A close correlation was found between LH and FSH when all patients were pooled (r = 0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating that the hypothalamus rather than the pituitary is the site of disturbance in gonadotrophin secretion. Serum SHBG was within normal limits and similar in all four groups. In nine females with alcoholic cirrhosis who abstained for 3 months, serum SHBG increased significantly from 39 ± 18 to 70 ± 25 nmol/l (p < 0.001), while LH increased in five of nine females and was unchanged in four. In conclusion, half of the amenorrhoeic females with alcoholic as well as non-alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating dysfunction of the hypothalamo–pituitary axis. The GnRH test indicated that disturbed hypothalamic function was the cause of the decreased LH and FSH secretion.
Helge Bell, Department of Medicine, Aker University Hospital, Trondhjemsveien 235, 0514 Oslo, Norway
Altered glycosylation of pituitary gonadotropins in anorexia nervosa: an alternative explanation for amenorrhea
Authors: Tommaselli Antonio P , Valentino Rossella , Savastano Silvia , Randazzo Giacomino , Scalfi Luca , Contaldo Franco , Dorato Maurizio , Lombardi Gaetano 
Published: December 2008

Tommaselli AP, Valentino R, Savastano S, Randazzo G, Scalfi L, Contaldo F, Dorato M, Lombardi G. Altered glycosylation of pituitary gonadotropins in anorexia nervosa: an alternative explanation for amenorrhea. Eur J Endocrinol 1995;132:450–5. ISSN 0804–4643
To investigate the relevance of glycoprotein polymorphism to gonadotropin bioactivity in vivo, plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH), 17β-estradiol (E2), testosterone and sex hormone binding globulin (SHBG) levels in 17 amenorrheic women affected with anorexia nervosa (14–29 years) and 10 age-matched normally cycling women were evaluated. Plasma FSH and LH levels were assayed using radioimmunoassay (RIA) and immunoradiometric assay (IRMA) methods, before and after concanavalin A–Sepharose (Con A) affinity chromatography. Significant RIA–IRMA differences in FSH and LH plasma values were present only in women with anorexia nervosa (p < 0.005). Moreover, in these patients both FSH and LH showed a reduced binding to the Con A, expressed as a percentage of unbound, suggesting altered glycosylation of these moieties. In conclusion, these findings hypothesize the involvement of glycosylation polymorphism in RIA-IRMA differences; support the usefulness of both RIA and IRMA methods in FSH and LH evaluation, before and after Con A chromatography; and suggest a new pathogenetic pathway to explain amenorrhea in anorexia nervosa.
Antonio P Tommaselli, Chair of Endocrinology, University Federico II, via Pansini, 5, 80131-Naples, Italy