bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide
Authors: Ezzat Shereen , Kontogeorgos George , Redelmeier Donald A , Horvath Eva , Harris Alan G , Kovacs Kalman
Published: December 2008

Ezzat S, Kontogeorgos G, Redelmeier DA, Horvath E, Harris AG, Kovacs K. In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide. Eur J Endocrinol 1995;133:686–90. ISSN 0804–4643

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 μg/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 ± 9% by octreotide, to 30 ± 7% by surgery and to 26 ± 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 ± 16% and to 24 ± 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 ± 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.

Shereen Ezzat, University of Toronto-Wellesley Hospital, 160 Wellesley St East, Toronto, Ontario M4Y-1J3, Canada
Melatonin enhances cortisol levels in aged but not young women
Authors: Cagnacci Angelo , Soldani Renza , Yen Samuel SC
Published: December 2008

Cagnacci A, Soldani R, Yen SSC. Melatonin enhances cortisol levels in aged but not young women. Eur J Endocrinol 1995;133:691–5. ISSN 0804–4643

In spite of animal data showing an effect of melatonin in the regulation of the hypothalamus–pituitary–adrenal (HPA) axis, no effect of melatonin on cortisol has been evidenced in young men. Gender and aging are believed to influence the regulation of the HPA axis, and may thus modulate the melatonin effect on cortisol. In this study we investigated whether an effect of melatonin on cortisol can be observed in women of different age. Six young women in early follicular phase (22–32 years; EFW) and eight aged women in postmenopause (54–62 years; PMW) were studied. At 08.00 h on two consecutive days each woman received, randomly and in double-blind fashion, a pill of placebo or melatonin (100 mg). Serum levels of melatonin and cortisol were evaluated at 20-min intervals for 48 h. In comparison to EFW, PMW showed an earlier onset of nocturnal melatonin (p < 0.05) and cortisol rise (p < 0.01) and higher cortisol levels at lunch (p < 0.05) and early evening (p < 0.01). Melatonin administration did not modify serum cortisol levels in EFW but elicited a marked increase of daytime cortisol levels in PMW (p < 0.02). The present data reveal that in aged PMW the cortisol levels are enhanced at selected circadian times and are stimulated by melatonin.

Angelo Cagnacci, Istituto di Ginecologia e Ostetricia, Ospedale 5, Giovanni di Dio, via Ospedale 46, 09124 Cagliari, Italy
No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide
Authors: Lasco Antonino , Cucinotta Domenico , Gigante Alfonso , Denuzzo Giulia , Pedulla Marilena , Trifiletti Aldo , Frisina Nicola
Published: December 2008

Lasco A, Cucinotta D, Gigante A, Denuzzo G, Pedulla M, Trifiletti A, Frisina N. No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide. Eur J Endocrinol 1995;133:718–22. ISSN 0804–4643

The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic–hyperinsulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome.

A Lasco, Via Faustina e Tertullo 19, 98100 Messina, Italy
Effects of epidermal growth factor and transforming growth factor alpha on the mouse trophoblast outgrowth in vitro
Authors: Machida Toshifumi , Taga Michiyoshi , Minaguchi Hiroshi
Published: December 2008

Machida T, Taga M, Minaguchi H. Effects of epidermal growth factor and transforming growth factor alpha on the mouse trophoblast outgrowth in vitro. Eur J Endocrinol 1995;133:741–6. ISSN 0804–4643

In order to analyze the involvement of growth factors in the implantation mechanism, we examined the direct effects of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) on trophoblast outgrowth of the mouse blastocyst in vitro. ICR mouse blastocysts were cultured for 4 days on a culture plate in medium containing EGF or TGF-α or conditioned medium obtained from cultured endometrial epithelial cells. Blastocysts were also co-cultured with endometrial epithelial cells. The trophoblast outgrowth of these cultured blastocysts was observed daily and the percentage of outgrowing embryos was calculated and analyzed statistically by the chi-squared test. Analysis for the specific binding of 125I-EGF in outgrown trophoblasts was carried out by autoradiography. The coculture (days 3 and 4) and the presence of EGF (10 ng/ml, day 4), TGF-α (1 ng/ml, day 3; 10 ng/ml, days 2 and 3; 50 ng/ml, days 2–4) or conditioned medium (days 3 and 4) significantly stimulated the rate of trophoblast outgrowth. Preincubation of the conditioned medium with monoclonal anti-EGF or anti-TGF-α antibody suppressed the stimulatory effect of the conditioned medium on trophoblast outgrowth. The specific 125I-EGF binding in outgrown trophoblasts was demonstrated by autoradiography. These results suggest that EGF and TGF-α play an important role in the implantation process by directly stimulating trophoblast development.

Michiyoshi Taga, Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan
Angiotensin II modulates steroidogenesis in granulosa and theca in the rabbit ovary: its possible involvement in atresia
Authors: Féral C , Le Gall S , Leymarie P
Published: December 2008

Féral C, Le Gall S, Leymarie P. Angiotensin II modulates steroidogenesis in granulosa and theca in the rabbit ovary: its possible involvement in atresia. Eur J Endocrinol 1995;133:747–53. ISSN 0804–4643

Accumulating evidence has shown the ovary of mammals to contain an intrinsic renin–angiotensin system that has been ascribed an autocrine-paracrine role. The present study in the female rabbit ovary investigated the putative in vitro action of angiotensin II (A II) on basal and gonadotropin-induced steroidogenesis. Ovarian follicles from immature female rabbits treated with pregnant mare's serum gonadotropin (PMSG) were dissected out and a complete separation of the theca interna from the granulosa layer was performed, to demonstrate that A II affects separately the two individual cellular components of the follicular wall. We could show that theca is a source of estradiol whose production under human chorionic gonadotropin (hCG) stimulation was reduced by A II. At the same time, A II increased the in vitro hCG-stimulated secretion of testosterone by theca. In granulosa, A II decreased hCG-stimulated aromatization of androstenedione to estradiol but did not alter the release of hCG-stimulated progesterone production. These results suggest that A II could induce locally an increase in follicular fluid androgen/estrogen ratio and possibly participate in causing atresia.

C. Féral, EP CNRS 009, Laboratoire de Biochimie, CHU Caen, F-14032 Caen Cedex, France
An open 36-month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency
Authors: Garry P , Collins P , Devlin JG
Published: December 2008

Garry P. Collins P. Devlin JG. An open 36 month study of lipid changes with growth hormone in adults: lipid changes following replacement of growth hormone in adult acquired growth hormone deficiency. Eur J Endocrinol 1996:134:61–6. ISSN 0804–4643

Interest in adult growth hormone replacement has increased since identification of the associated vascular morbidity and mortality. Although total cholesterol and low density lipoprotein reduction and high density lipoprotein increases are anticipated, reports are conflicting and there is no uniformity in lipoprotein(a) changes. In 1990 we commenced an open trial of therapy with human recombinant GH and now have results to 36 months for 21 patients. Deficiency status was confirmed by insulin stress test with flat GH response <2.0 ng/ml, mean insulin-like growth factor-I value 122 ng/ml (±69 SD). Lipoprotein(a) was measured by monoclonal assay. Lipid analysis yields two subgroups: baseline cholesterol levels of greater or less than 6.22 mmol/l, with hypercholesterolaemic patients showing an enhanced hypolipaemic response. ANOVA was utilized, with 95% confidence limits. The most significant changes are of reductions in cholesterol and low density lipoprotein: the rate of change is greatest at 6 and 12 months but not sustained to 36 months. High density lipoprotein rises as expected, not to full significance. Lipoprotein(a) levels rose significantly in six patients of the cohort, and the increase was sustained over 36 months.

JG Devlin, Department of Endocrinology, Beaumont Hospital. Dublin 9. Ireland
Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy; demonstration of direct binding of autoantibodies to the thyrotropin receptor
Authors: Tonacchera Massimo , Costagliola Sabine , Cetani Filomena , Ducobu Jean , Stordeur Patrick , Vassart Gilbert , Ludgate Marian
Published: December 2008

Tonacchera M. Costagliola S, Cetani F, Ducobu J. Stordeur P. Vassart G. Ludgate M. Patient with monoclonal gammopathy, thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy: demonstration of direct binding of autoantibodies to the thyrotropin receptor. Eur J Endocrinol 1996:134:97–103. ISSN 0804–4643

We describe a patient with monoclonal gammopathy who subsequently developed thyrotoxicosis, pretibial myxedema and thyroid-associated ophthalmopathy. The pathogenesis of thyrotoxicosis in Graves' disease is due to the presence of autoantibodies that mimic the action of thyrotropin (TSH). called thyroid-stimulating antibodies (TS-ab): these antibodies may or may not inhibit the binding of TSH to the receptor (thyroid-binding inhibiting immunoglobulin, TBII). The patient's immunoglobulins were TS-ab positive and TBII negative when measured on CHO cells expressing the human TSH receptor. The pathogenetic link between the thyroid, orbit and skin is yet to be established but several candidate shared antigens have been proposed, including the TSH receptor itself. The monoclonal immunoglobulins were in evidence before the symptoms of pretibial myxedema, thyrotoxicosis and ophthalmopathy, In addition, the patient had no autoantibodies to thyroglobulin or thyroperoxidase, which are classic markers of thyroid autoimmunity. This combination led us to postulate that the monoclonal gammopathy could be the cause of all the observed pathology. One method to test this hypothesis would be to show that the monoclonal immunoglobulin is a TS-ab. Various methods were used to separate the monoclonal from the polyclonal components of the patient's serum. Preparative isoelectric focusing enabled us to obtain fractions containing only the monoclonal (as revealed by polyacrylamide gel electrophoresis), which were devoid of TS-ab activity (measured as cAMP accumulation in CHO cells expressing the human TSH receptor in a hypotonic bioassay). Subsequently, different oligoclonal fractions were shown to have varying degrees of TS-ab activity, with one fraction having faint biological activity and able to recognize a recombinant TSH receptor preparation in a Western blot. In conclusion, the monoclonal antibody does not seem to be responsible for the thyrotoxicosis, pretibial myxedema and ophthalmopathy. We confirm previous data showing that TSH receptor antibodies in patients with Graves' disease are heterogeneous in nature and we present the first demonstration of autoantibodies capable of binding the TSH receptor but devoid of TBII activity.

Massimo Tonacchera, Institut de Recherche Interdisciplinaire, Université Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, 1070 Bruxelles
Thyroid hormone induces the generation of a novel putative protein in piscine ovarian follicle that stimulates the conversion of pregnenolone to progesterone
Authors: Bhattacharya S , Guin S , Bandyopadhyay A , Jana NR , Halder S
Published: December 2008

Bhattacharya S, Guin S, Bandyopadhyay A, Jana NR, Halder S. Thyroid hormone induces the generation of a novel putative protein in piscine ovarian follicle that stimulates the conversion of pregnenolone to progesterone. Eur J Endocrinol 1996:134:128–35. ISSN 0840–4643.

Ovarian follicles were collected from the perch belonging to the vitellogenic stage and incubated in vitro for 4 h in the absence (control) or presence of triiodothyronine (T3). Addition of T3 (40 ng/ml) to the follicle incubation caused a two-fold increase of [3H] pregnenolone conversion to radiolabelled progesterone (P4) as compared to the control. The increase in P4 formation in the ovarian follicle could be blocked completely by the inhibitors of protein synthesis, actinomycin D and cycloheximide (50 μg/ ml), suggesting a protein or peptide mediator of the T3 stimulatory effect. To search for this mediator, ovarian follicles from the control or T3 incubate were homogenized and ultracentrifuged and different fractions were added separately to fresh follicle incubations. Only the 100 000g supernatant from T3 incubate showed a significant (p < 0.01) increase in P4 formation, while the corresponding supernatant from control follicle incubations had no such stimulatory effect. Trypsin or heat destroyed this augmentory effect. Based on its ability to stimulate the conversion of radiolabelled pregnenolone to P4 in the ovarian follicle, the T3-induced protein (TIP) was purified to homogeneity by employing Sephadex G-75 gel filtration, FPLC Mono-Q and FPLC Superose-6 chromatography. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of purified TIP showed it to be a 52 K monomer protein. Addition of TIP in increasing concentrations to follicle incubations caused a linear increase in P4 formation. Experiments with radiolabelled TIP ([125 I] TIP) indicate its entry through the follicular cell membrane within the limited period of incubation. Results suggest that TIP activates ovarian 3β-hydroxysteroid dehydrogenase enzyme, thus effecting a greater conversion of pregnenolone to P4.

S. Bhattacharya, Department of Zoology, Visva-Bharati University. Santiniketan 731 235, West Bengal, India
Bone mineral density in immigrants from southern China to Denmark. A cross-sectional study
Authors: Wang Q , Ravn P , Wang S , Overgaard K , Hassager C , Christiansen C
Published: December 2008

Wang Q, Ravn P, Wang S, Overgaard K, Hassager C, Christiansen C. Bone mineral density in immigrants from southern China to Denmark: a cross-sectional study. Eur J Endocrinol 1996;134:163–7. ISSN 0804–4643

Immigration from Japan to USA has been shown to increase bone mineral density (BMD) and body fat in women. The effects of immigration between other geographical areas on bone mass and body composition are largely unknown, especially in men. In the present study, we measured bone mass and body composition by dual energy X-ray absorptiometry (Hologic QDR-2000) in 73 healthy premenopausal women (age 35 ± 8 years) and 69 men (age 40 ± 12 years) who had immigrated from southern China to Denmark 2 months to 36 years ago. The BMD measurements (Total BMD, trunk BMD and leg BMD) were related positively to years since immigration (YSI) (R2 = 0.10–0.16, p < 0.05) in premenopausal women, but not in men. Fat distribution was related mainly to age in both premenopausal women and men (R2 = 0.16–0.26, p < 0.05). For comparison, we included 51 white, Danish premenopausal women (age 36 ± 6 years). Chinese premenopausal women with a YSI below or equal to 12 years (N = 38) had significantly lower total and regional BMD (trunk, legs, arms) (p < 0.05), while women with a YSI above 12 years (N = 35) had significantly lower BMD in the legs only (p < 0.05) when compared to the Danish premenopausal women. After correction for age, weight and height, Chinese premenopausal women with a YSI below or equal to 12 years still had significantly lower BMD in all regions (4–7%, p < 0.05), whereas no differences in BMD were found between Chinese premenopausal women with a YSI above 12 years compared with Danish premenopausal women. In conclusion, Chinese premenopausal women who immigrated to Denmark more than 12 years ago have a similar BMD to that of Danish premenopausal women. In the group who immigrated less than 12 years ago, a significantly lower BMD was found.

P Ravn, Center for Clinical and Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark
Body composition and energy expenditure in thyroidectomized patients during short-term hypothyroidism and thyrotropin-suppressive thyroxine therapy
Authors: Wolf Matthias , Weigert Andrea , Kreymann Georg
Published: December 2008

Wolf M, Weigert A, Kreymann G. Body composition and energy expenditure in thyroidectomized patients during short-term hypothyroidism and thyrotropin-suppressive thyroxine therapy. Eur J Endocrinol 1996;134:168–73. ISSN 0804–4643

Thyroid hormone levels are a major determinant of energy balance and are thought to modify body composition by their effects on metabolism of lipids, carbohydrate and protein. The present study evaluates changes of body composition and basal energy expenditure (BEE) in thyroidectomized patients studied during short-term profound hypothyroidism while off all thyroid hormone before diagnostic whole-body I-imaging and while on thyrotrophin-suppressive thyroxine therapy. Basal energy expenditure was assessed by indirect calorimetry, and four-point body impedance analysis was used to estimate body composition. Patients were compared with healthy controls matched with respect to sex, age, height and weight. Compared to healthy controls the percentages of body water and body cell mass were significantly lower while the percentage of fat was significantly higher in patients during short-term hypothyroidism. Weight did not change significantly when patients were put on thyroxine treatment, but body fat (–0.95 ± 2.25 kg, p < 0.01) decreased while body water (+0.94 ± 1.31 kg, p < 0.01) and body cell mass (+0.9 ± 2.5 kg, p < 0.05) increased. With thyroxine replacement, body composition was not significantly different between patients and controls. Compared to healthy controls, BEE was significantly lower in patients without thyroxine replacement (5265 ± 766 kJ/24 h vs 6362 ± 992 kJ/24 h; p < 0.001). With thyroxine treatment, BEE increased (6492 ± 967 kJ/24 h) but was not significantly different from the controls (p 0.05). Neither body composition nor BEE was significantly different in a subgroup of thyroxine-treated patients with free triiodothyronine or thyroxine values above the normal range. In conclusion, both body composition and energy expenditure showed significant changes when patients were deprived of thyroid hormone. However, no evidence of excess metabolic effects of thyroid hormone during thyrotrophin-suppressive thyroxine therapy was found.

Matthias Wolf, Medizinische Kern- und Poliklinik, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Secretory rhythm of vasopressin in healthy subjects with inversed sleep–wake cycle: evidence for the existence of an intrinsic regulation
Authors: Nadal Miguel
Published: December 2008

Nadal M. Secretory rhythm of vasopressin in healthy subjects with inversed sleep–wake cycle: evidence for the existence of an intrinsic regulation. Eur J Endocrinol 1996;134:174–6. ISSN 0804–4643

The objective of this paper was to find out if the higher night levels of vasopressin described in previous studies are a manifestation of a permanent and stable rhythm bound to the different periods of the day or if they are independent of them and due to other causes. Vasopressin secretion was studied in a group of seven healthy subjects with an inverted sleep–wake cycle (night workers who sleep and rest during the day). The study was performed during the last week of their working period after at least 3 weeks of continuous night shift. Plasma samples for vasopressin determination were taken every 4 h during a 24-h period while the subjects were performing their normal night work and with their usual sleeping habits during the day. Plasma osmolality, electrolytes and blood pressure were also assessed during the test. In contrast to previous studies where higher nocturnal values have been reported, we found significantly higher vasopressin levels during the day, giving as a whole a characteristic pattern with the highest vasopressin levels measured at 16.00 h followed by a progressive decrement that reached its nadir at 04.00 h. The total measured secretion of vasopressin was significantly higher during the day than during the night (p = 0.0313). No significant difference was found, on the other hand, between day samples, with the exception of samples taken at 16.00 h and at 12.00 h (p = 0.031). Plasma osmolality and electrolytes were within the normal range during the test and no statistical difference was observed at the various points. It was concluded that the secretion of vasopressin is higher during sleep and rest time and lower during the active part of the 24 h. The secretory pattern of vasopressin is not bound to the different periods of the day as such, nor to variations in plasma osmolality or electrolytes. It seems therefore reasonable to assume that the secretion of vasopressin has an intrinsic daily rhythm that is not related to known regulatory agents but is modulated by other unidentified factors. Several hypotheses are discussed.

Miguel Nadal, Department of Internal Medicine (Endocrinology), Skellefteå Hospital, S-931 86 Skellefteå, Sweden
Low frequency of p53 mutations in human thyroid tumors; p53 and Ras mutation in two out of fifty-six thyroid tumours
Authors: Salvatore Domenico , Celetti Angela , Fabien Nicole , Paulin Christian , Martelli Maria Luisa , Battaglia Caterina , Califano Daniela , Monaco Carmen , Viglietto Giuseppe , Santoro Massimo , Fusco Alfredo
Published: December 2008

Salvatore D, Celetti A, Fabien N, Paulin C, Martelli ML, Battaglia C, Califano D, Monaco C, Viglietto G, Santoro M, Fusco A. Low frequency of p53 mutations in human thyroid tumors; p53 and Ras mutation in two out of fifty-six thyroid tumours. Eur J Endocrinol 1996;134:177–83. ISSN 0804–4643

Objective: p53 is a well-known nuclear phosphoprotein encoded by a suppressor gene known to be mutated in various kinds of human tumours. A relationship between p53 gene mutation and tumour progression seems to be a common feature of several neoplasias. Desing: In order to investigate the role of p53 mutations in human thyroid tumours, DNA samples derived from fifty-six neoplastic tissues, ranging from benign adenomas to undifferentiated carcinomas, were examined for the presence of p53 gene mutations. Methods: The analysis has been conducted using polymerase chain reaction (PCR) amplification of the exons 5–9 of the p53 gene followed by single strand conformation polymorphism (SSCP) and sequence analyses. Results: One anaplastic carcinoma and one papillary carcinoma showed p53 gene mutations in exons 5 and 8, respectively. A cell line established from the papillary carcinoma showed the same mutation present in the original tumour. Both p53 mutations were heterozygous. The p53 positive samples were analysed for other genetic alterations frequently detected in human thyroid carcinomas (mutations of the RET, TRK, and ras oncogenes): both p53-mutated samples proved to be mutated at level of codon 13 of the c-Ki-ras gene. Conclusions: Our data confirm that p53 gene alterations are rare in well-differentiated thyroid tumours, that they are an important requirement for the establishment in culture of human thyroid carcinoma cell lines, and that they can be associated with other genetic alterations, namely ras mutations, in the malignant progression of thyroid tumours.

Alfredo Fusco, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, via S. Pansini 5, 80131, Napoli, Italy
Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured rat hepatocytes
Authors: Pellizas Claudia G , Coleoni Aldo H , Cabanillas Ana M , Masini-Repiso Ana M , Costamagna María E
Published: December 2008

Pellizas CG, Coleoni AH, Cabanillas AM, Masini-Repiso AM, Costamagna ME. Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured cat hepatocytes. Eur J Endocrinol 1996:134:215–20. ISSN 0804–4643

Triiodothyronine (T3) is involved in the regulation of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis. In this study we investigated the effect of GH and IGF-I on the metabolic response of T3 in target tissues by evaluating the activity of two T3-dependent liver enzymes: mitochondrial α-glycerophosphate dehydrogenase (α-GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary culture. Growth hormone (35 nmol/l) as well as IGF-I (0.5 μmol/l) reduced α-GPD and ME activities (p < 0.01) compared to the control group. Timecourse studies indicated that IGF-I 1.5 μmol/l) significantly decreased α-GPD and ME activities (p < 0.01) after 24 h, whereas the effect of GH (35 nmol/l) was recorded only after 36 h (p < 0.01). This delayed effect of GH compared to IGF-I suggested the possibility that the effect of GH could be mediated by IGF-I synthesis. To test this hypothesis, the effect of GH on the two enzyme activities was studied in the presence of anti-IGF-I antibodies. A gradual recovery of α-GPD and ME activities (p < 0.01) was observed in the presence of GH (35 nmol/l) plus increasing concentrations of anti-IGF-I antiserum. The maximal α-GPD and ME activities attained after the incubation of the liver cells with 1 μmol/l T3. a concentration high enough to fully saturate the nuclear T3 receptors for 24 h, were lowered significantly by 1.0 μmol/l IGF-I (p < 0.01). This finding suggests that the IGF-I effect might be independent of the saturation of the nuclear T3 receptors. In conclusion, in cultured rat hepatocytes, GH and IGF-I reduced the metabolic response of T3 evaluated by two liver T3-dependent enzyme activities. The effect of GH was mediated at least in part by IGF-I.

Claudia G Pellizas, Dpto Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Códoba, Casilla de Correo 61, Sucursal 16, (5016) Córdoba, Argentina.
Effects of 5,5′-diphenylhydantoin on the thyroid status in rats
Authors: Schröder-van der Elst JP , van der Heide D , van der Bent C , Kaptein E , Visser TJ , DiStefano JJ
Published: December 2008

Schröder-van der Elst JP, van der Heide D, van der Bent C, Kaptein E, Visser TJ, DiStefano JJ, Effects of 5,5′diphenylhydantoin on the thyroid status in rats. Eur J Endocrinol 1996;134:221–4. ISSN 0804–4643

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels. To investigate if this is accompanied by tissue hypothyroidism, rats were treated for 3 weeks with DPH (50 mg/kg body wt in food). Thyroid hormone-dependent parameters were measured, and the results were compared to those of control rats and to those of athyreotic rats substituted with thyroxine + triiodothyronine (Tx + TH) to reach the same plasma TH levels as DPH-treated rats. These rats were mildly hypothyroid with regard to their TH and TSH levels and TH-dependent parameters. Both DPH and Tx + TH led to a decrease in plasma thyroxine (T4) and triiodothyronine (T3) (±70% of the control). The percentage free T4 was unchanged. Plasma thyrotropin (TSH) was increased only in the Tx + TH rats (sixfold). For DPH rats, pituitary hormone content was not different from the control; growth hormone was lower and TSH was higher in Tx + TH rats. In DPH and Tx + TH rats, an increase in hepatic T4 and T3 uridine-diphosphate glucuronyltransferase activity was found, likewise indicating a change in the metabolic pathway of TH. Hepatic iodothyronine deiodinase (ID) type I activity decreased in Tx + TH rats but did not alter in DPH rats. Hepatic α-glycerophosphate dehydrogenase (α-GPD) decreased in DPH and Tx + TH rats. Malic enzyme in liver was enhanced in DPH rats. In the brains of DPH rats the level of α-GPD activity was raised; in Tx + TH it was lowered. The ID type II activity in the brain was reduced in DPH rats, but ID type III did not change for either group. Total body oxygen consumption increased in DPH rats (13%); it decreased in Tx + TH rats (9%). Our results show that DPH causes changes comparable to mild hypothyroidism. The lack of or a diminished hypothyroid response can be explained as the attenuating agonistic effect of DPH, which is supported by O2 consumption, brain ID type II and α-GPD activities. The T4 content was reduced by 30% in thyroid digests; this, together with a reduced T4 secretion, can lead to serious hypothyroxinemia during prolonged DPH treatment.

JP Schröder-van der Elst, Department of Metabolic Diseases and Endocrinology, Building 1, C4-R, University Hospital, Rijnsburgerweg 10, 2300 RC Leiden, The Netherlands
Progesterone together with estradiol promotes luteinizing hormone β-subunit mRNA stability in rat pituitary cells cultured in vitro
Authors: Park Deokbae , cheon Minseok , Kim Changmee , Kim Kyungjin , Ryu Kyungza
Published: December 2008

Park D, Cheon M, Kim C, Kim K, Ryu K. Progesterone together with estradiol promotes luteinizing hormoneβ-subunit mRNA stability in rat pituitary cells in vitro. Eur J Endocrinol 1996;134:236–42. ISSN 0804–4643

The present study examined the role of ovarian steroids, estradiol and/or progesterone in the regulation of luteinizing hormone β-subunit (LH-β) mRNA levels and LH release in the rat anterior pituitary cells cultured in vitro. When estradiol (10 nmol/l and/or progesterone (100 nmol/l) were added to the cultures, neither estradiol or progesterone nor both together altered the basal LH-β mRNA levels or LH release. Continuous exposure to gonadotropin-releasing hormone (GnRH, 0.2 nmol/l) for 24 h markedly induced LH-β mRNA accumulation, and in this experimental condition, progesterone alone and progesterone + estradiol further augmented GnRH-induced LH-β mRNA levels and LH release. Then we explored further the possibility that ovarian steroids are involved in modulating LH-β mRNA stability in cultured rat pituitary cells where transcription was inhibited by actinomycin D. Anterior pituitary cells were preincubated with GnRH (0.2 nmol/l) for 16 h and, after removing GnRH from culture medium, the cells were incubated further in the presence of actinomycin D (5 μmol/l) for 24 h. The LH-β mRNA levels gradually declined to about 30% of the control values (zero time point after GnRH removal) in a time-dependent manner. During this period, either progesterone alone or progesterone + estradiol clearly blocked the degradation of LH-β mRNA species. These results indicate that ovarian steroids promote LH-β mRNA stability, thereby contributing to the maintenance of GnRH-stimulated LH-β mRNA levels.

Kyungza Ryu, Department of Pharmacology, College of Medicine, Yonsei University, 120-749, Seoul, Korea
Interleukin-1β-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine
Authors: Andersen Henrik U , Mauricio Dídac , Karlsen Allan E , Mandrup-Poulsen Thomas , Nielsen Jens H , Nerup Jørn
Published: December 2008

Andersen HU, Mauricio D, Karlsen AE, Mandrup-Poulsen T, Nielsen JH, Nerup J. Interleukin-nitric oxide production from isolated rat islets is modulated by d-glucose and 3-isobutyl-1-methyl xanthine. Eur J Endocrinol 1996:134:251–9. ISSN 0804–4643

Interleukin-1β has been proposed to cause selective β-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1β is modulated by the concentration of d-glucose in the medium. The aim of this study was to investigate if d-glucose-mediated modulation of interleukin-1β effects on insulin release from isolated rat islets was related to modulation of nitric oxide production. Further, we wished to investigate the effects of agents increasing the intracellular concentration of cAMP on interleukin-1β-induced nitrite production. We demonstrated that d-glucose potentiated interleukin-1β-induced nitrite production in rat islets without affecting the mRNA level of the inducible nitric oxide synthase. This effect was dissociated from interleukin-1β action on insulin release, since a relative protection against interleukin-1β effects on acute insulin release was found at high (28 mmol/l) concentrations of d-glucose, and blocking nitrite production by the L-arginine analog aminoguanidine, which selectively inhibits the cytokine-inducible nitric oxide synthase, did not result in protection against the inhibitory action of interleukin-1β Neither l-glucose nor the secretagogues l-leucine, tolbutamide and β-isobutyl-1-methyl xanthine shared the potentiating effect of d-glucose, The phosphodiesterase inhibitor β-isobutyl-1-methyl xanthine reduced interleukin-1β-induced nitrite production at 3.3 mmol/l d-glucose, an effect that could be reproduced by the cAMP analog dibutyryl cAMP. Addition of 3-isobutyl-1-methyl xanthine resulted in a threefold reduction in the mRNA level of interleukin-1β-induced inducible nitric oxide synthase. We conclude that interleukin-1β-induced islet nitric oxide synthesis is augmented by d-glucose but not by non-substrate secretagogues, and that secretagogues that elevate cAMP inhibit islet nitric oxide production.

Jørn Nerup, Steno Diabetes Center, Niels Steensens vej 2, DK-2820 Gentofte, Denmark
Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism
Authors: Sheaves Richard , Goldin Jonathan , Reznek Rodney H , Chew Shern L , Dacie Janet E , Lowe David G , Ross Richard JM , Wass John AH , Besser G Michael , Grossman Ashley B
Published: December 2008

Sheaves R, Goldin J, Reznek RH, Chew SL, Dacie JE, Lowe DG, Ross RJM, Wass JAH, Besser GM, Grossman AB, Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism. Eur J Endocrinol 1996;134:308–13. ISSN 0804–4643

The purpose of this study was to evaluate the relative merits of the postural stimulation test, adrenal computed tomography (CT) and venous sampling in the differential diagnosis of patients presenting with primary hyperaldosteronism. The records of 20 patients presenting with primary hyperaldosteronism were reviewed retrospectively. There were 15 patients with a unilateral aldosterone-producing adenoma (APA), four patients with idiopathic hyperaldosteronism (IHA) and one patient with primary adrenal hyperplasia (PAH). The postural stimulation test was based on measurements of plasma aldosterone and renin activity at 08.00 h and at noon after 4 h of ambulation. The CT scans of the adrenals were reviewed by a single radiologist. Bilateral venous sampling of adrenal veins was attempted in all patients and blood collected for aldosterone and cortisol assay. Plasma aldosterone concentration increased after 4 h of standing in all cases of hyperplasia but was also demonstrated in 10/15 patients with a surgically-proven APA, If one defines a significant postural rise as being greater than 30%, then 8/15 patients with APA can be considered as being posturally responsive. Computed tomography scanning correctly identified all 15 cases of APA and also classified correctly the remaining five cases of hyperplasia (four cases of IHA and one case of PAH). Venous sampling failed technically in 4/15 cases of APA and in one case of IHA; a total of 5/20 (25%), A correct diagnosis of APA or IHA was established in all the remaining cases. However, the one case of PAH was treated successfully by adrenalectomy following venous sampling, which suggested a unilateral adrenal lesion: this one result was the only instance where venous sampling altered clinical decision-making. Computed tomography scanning may be used alone to confirm the cause of hyperaldosteronism where postural studies suggest an adrenal adenoma, and such patients may be considered for early surgery. Venous catheterization studies are not necessary routinely, but may still be useful in selected patients, particularly when CT scanning shows no clear lesion.

Ashley Grossman, Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London ECIA 7BE, UK
Increased plasma levels of islet amyloid polypeptide in patients with primary hyperparathyroidism
Authors: Valdemarsson Stig , Leckström Arnold , Westermark Per , Bergenfelz Anders
Published: December 2008

Valdemarsson S, Leckström A, Westermark P, Bergenfelz A. Increased plasma levels of islet amyloid polypeptide in patients with primary hyperparathyroidism. Eur J Endocrinol 1996;134:320–5. ISSN 0804–4643

Amylin, also named islet amyloid polypeptide (IAPP), is a protein that is processed and released from pancreatic β-cells in parallel with insulin. Islet amyloid polypeptide is currently studied with regard to a role for insulin resistance in non-insulin-dependent diabetes. To elucidate a possible function of IAPP for impaired glucose tolerance in primary hyperparathyroidism (pHPT), we studied plasma IAPP levels during an oral glucose tolerance test (OGTT) in seven pHPT patients before and 8 weeks after surgery and in six healthy subjects. The β-glucose level of the patient groups was 4.34 ± 0.12 mmol/l before and 3.97 ± 0.16 mmol/l after surgery (NS), while the serum level of insulin was significantly higher before (16.9 ± 2.8 mIU/l) than after (8.9 ± 1.9 mIU/l) the operation (p < 0.05), indicating a moderately increased insulin resistance in pHPT. The basal plasma levels of IAPP were significantly higher in pHPT patients before than 8 weeks after surgery (9.71 ± 1.05 and 4.30 ± 0.82 pmol/l, respectively; p < 0.01). When compared to the plasma IAPP level of the controls at 1.80 ± 0.38 pmol/l, pHPT patients had higher IAPP values both before (p < 0.01) and at 8 weeks after (p < 0.05) operation, There was a significant correlation between the serum levels of insulin and plasma levels of IAPP in pHPT patients before (r = 0.87, p < 0.01) as wells as 8 weeks after surgery (r = 0.69, p < 0.05). The area under the curve for IAPP during OGTT in pHPT patients was 1872.4 ± 187.7 pmol·min/l, which is significantly higher than after surgery 1010.8 ± 93.7 pmol· min/l) (p < 0.05) and compared to the area for the controls at 840.3 ± 49.9 pmol min/l (p< 0.01). In conclusion, pHPT is associated with an increased plasma level of IAPP, correlated to the serum insulin level, but persistently higher than in controls also 8 weeks after surgery. Possibly, increased IAPP levels can have a role for impaired glucose tolerance in pHPT. The hyperparathyroid state might have a specific role for the release of this peptide, otherwise closely connected to insulin secretion.

Stig Valdemarsson, Department of Internal Medicine, Lund University Hospital, S-221 85 Lund, Sweden
Peptide YY does not inhibit glucose-stimulated insulin secretion in humans
Authors: Ahrén Bo , Larsson Hillevi
Published: December 2008

Ahrén B, Larsson H. Peptide YY does not inhibit glucose-stimulated insulin secretion in humans. Eur J Endocrinol 1996;134:362–5. ISSN 0804–4643

Peptide YY (PYY) is localized to gut and pancreatic endocrine cells. It may therefore be involved in the regulation of insulin secretion as a gut hormone as well as an islet local regulator. In laboratory animals, the peptide inhibits stimulated insulin secretion, but its effects in humans are not known. We therefore infused PYY intravenously at a low (1 pmol·kg−1 · min−1; N = 4) or a high rate (5 pmol · kg−1 · min−1; N= 5) for 120 min in healthy women aged 52 years. After 30 min of infusion, glucose (0.5 g/kg) was injected rapidly. In separate control experiments, saline was infused instead of PYY. We found that PYY did not inhibit the acute insulin response to glucose or affect the glucose elimination rate, and PYY was also without influence on the basal plasma glucose and serum insulin levels during the 30-min infusion before the challenge with glucose. We therefore conclude that intravenous infusion of PYY does not affect glucose-stimulated insulin secretion in man.

Bo Ahrén, Department of Medicine, Malmö University Hospital, S-205 02 Malmö, Sweden
Differential subcellular distribution of rat prostatic steroid 5α-reductase isozyme activities
Authors: Span Paul N , Sweep CGJ , Benraad Theo J , Smals Anthony GH
Published: December 2008

Span PN, Sweep CGJ, Benraad TJ, Smals AGH. Differential subcellular distribution of rat prostatic steroid 5α-reductase isozyme activities. Eur J Endocrinol 1996;134:386–92. ISSN 0804–4643

The rat prostate, a classical androgen-target tissue, contains both known isozymes of steroid 5α-reductase, i.e. type I and type II. So far, the role of the type I isozyme has been proposed as catabolic. The abundant expression of type I 5α-reductase in an androgen-target tissue is therefore puzzling. Assessment of the subcellular localization of 5α-reductase isozymes in rat prostate might contribute in elucidating their possibly distinct roles. After obtaining crude subcellular fractions by differential centrifugation, both isozyme activities were measured at neutral pH by plotting according to Eadie–Scatchard. The observations were extended by assessment of pH-dependent velocity ratios and type II 5α-reductase inhibitor sensitivities in these subcellular fractions. The results indicated a preferentially—although not exclusively—nuclear localization for the type I and a predominantly microsomal localization for the type II isozyme activity in the rat prostate. In conclusion, the nuclear localization of the type I isozyme seems not to concur with its proposed catabolic role.

AGH Smals, Department of Medicine, Division of Endocrinology, University Hospital Nijmegen, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands
Major histocompatibility complex class II and complement polymorphisms in postpartum thyroiditis
Authors: Parkes Arthur B , Darke Christopher , Othman Sakinah , Thomas Melanie , Young Neil , Richards Colin J , Hall Reginald , Lazarus John H
Published: December 2008

Parkes AB, Darke C, Othman S, Thomas M, Young N, Richards CJ, Hall R, Lazarus JH. Major histocompatibility complex class II and complement polymorphisms in postpartum thyroiditis. Eur J Endocrinol 1996;134:449–53. ISSN 0804–4643

The objective was to re-evaluate the association between class II HLA-DR and DQ MHC antigens and postpartum thyroiditis (PPT) and to determine the prevalence of the class III complement allotypes of Properdin factor B (Bf), C4A and C4B in this condition. Two hundred and sixty-five (of 2897) pregnant women screened positive for thyroid autoantibody activity took part. Further blood samples were obtained for HLA class II (185) and complement (193) typing. The severity of the ensuing PPT was assessed by measuring thyroid function during the postpartum year. The HLA-DR and DQ phenotypes were assigned from restriction fragment length polymorphism analysis, and Bf, C4A and C4B allotypes were determined by immunofixation with anti-Bf or anti-C4 antibodies after electrophoresis. A weak association between the HLA class II antigens and PPT, as indicated by a reduced frequency of DR15 and DQ6 together with an increased frequency of DR5 and DQ7. was confirmed. However, only the change in DR5 frequency remained significant after correction (corrected p < 0.05). Postpartum thyroiditis was also associated with frequency disturbances in Bf and C4A allotypes but not C4B allotypes. Whilst this study has not provided evidence of a strong marker gene for PPT, it does not preclude the involvement of the MHC in this condition. These data show disturbances in complement allotype frequencies, suggesting that the class III region may provide a useful focus for further study of this pathology.

AB Parkes, Autoimmunology Research Unit, Section of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK
Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine
Authors: Delgrange Etienne , Maiter Dominique , Donckier Julian
Published: December 2008

Delgrange E, Maiter D, Donckier J. Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. Eur J Endocrinol 1996;134:454–6. ISSN 0804–4643

Cabergoline is a new long-acting ergoline derivative used to treat hyperprolactinaemia. Its effect was assessed in 10 patients (eight women and two men) with prolactinoma who were intolerant (group I; N = 7) or resistant (group II; N = 3) to bromocriptine. In group I, no side effect was observed on cabergoline therapy; two patients became pregnant and normoprolactinaemia was achieved in the five others. In group II, cabergoline was active and well-tolerated in two out of the three patients: one woman had three consecutive pregnancies; in another patient normoprolactinaemia was restored and the tumour shrank by 60%; in the third patient cabergoline was discontinued because of side effects and inefficacy. Thus, cabergoline appears to be an alternative of choice as treatment of hyper-prolactinaemic patients who are intolerant or resistant to bromocriptine.

Julian Donckier, Internal Medicine and Endocrinology, University Hospital UCL of Mont-Godinne, B-5530 Yvoir, Belgium