bluuebunny/crossref_metadata_2025_split huggingface dataset:
Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors
Authors: Hensen J , Haenelt M , Gross P 
Published: December 2008

Hensen J, Haenelt M, Gross P. Water retention after oral chlorpropamide is associated with an increase in renal papillary arginine vasopressin receptors. Eur J Endocrinol 1995;132:459–64. ISSN 0804–4643
Chlorpropamide (CP), a sulfonylurea used for treatment of non-insulin dependent diabetes mellitus, is known to potentiate the antidiuretic action of arginine vasopressin (AVP), predisposing to hyponatremia. It has been suggested that CP acts directly on the antidiuretic vasopressin receptor. Detailed studies on the influence of CP on the AVP receptor, however, have been hampered by lack of a suitable radioligand. Using a newly developed radioiodinated derivative of AVP with high specific activity and high affinity for the AVP V2-receptor (125I-[8-(p-(OH)-phenylpropionyl)]-LVP), we studied the role of AVP V2-receptors in CP-induced water retention. Male-Sprague-Dawley rats were treated orally with 40 mg CP/day or placebo for 7 days, after which Scatchard analysis was performed using membranes prepared from homogenized renal papilla. After oral water load, CP-treated rats but not control rats showed a significant decrease in plasma osmolality (289 ±2.2 to 284±0.8 mosmol/kg, p < 0.05). The Kd was 0.69 ± 0.16 nmol/l in controls and 0.70 ± 0.12 nmol/l after CP treatment (NS); Bmax was 129 ± 5.3 nmol/kg protein in controls (N = 8). Chlorpropamide significantly increased receptor density (Bmax) to 167±8.4 nmol/kg protein (N = 8) (p<0.05). Plasma AVP did not change significantly during CP treatment. These data show for the first time that CP in vivo increases the density of AVP V2 receptors without altering plasma AVP. This is associated with an impairment in water excretion. Our experiments and recent reports on CP-induced inhibition of AVP binding suggest that the AVP augmentation effect of CP is related to interference of CP with the AVP V2-receptor. Johannes Hensen, Department of Medicine I, Division of Endocrinology and Metabolism, Krankenhausstr. 12, 91054 Erlangen, Germany
Chronic stress and pituitary–adrenocortical responses to corticotropin-releasing hormone and vasopressin in female pigs
Authors: Janssens Cecile JJG , Helmond Frans A , Wiegant Victor M 
Published: December 2008

Janssens CJJG, Helmond FA, Wiegant VM. Chronic stress and pituitary–adrenocortical responses to corticotropin-releasing hormone and vasopressin in female pigs. Eur J Endocrinol 1995;132:479–86. ISSN 0804–4643
Effects of long-term tethered housing (a condition of chronic stress) on pituitary-adrenocortical responsiveness to exogenous corticotropin-releasing hormone (CRH) and lysine8-vasopressin (LVP) were investigated in female pigs. Intravenous administration of CRH (dose range 10–440 pmol/kg body wt) or LVP (10–880 pmol/kg body wt) elicited transient and dose-related increases in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol. Comparison of the responses induced by the peptides indicated that CRH is a more potent ACTH secretagogue than LVP. Treatment with LVP produced a fivefold greater plasma cortisol/ACTH ratio than treatment with CRH, suggesting that in addition to stimulating pituitary ACTH release it enhanced the ability of the adrenal cortex to secrete cortisol in response to ACTH. Whereas concomitant administration of 10 pmolCRH/kg body wt and 20 pmol LVP/kg body wt revealed an additive effect on ACTH release, synergism between both peptides was found with respect to their cortisol-releasing effect. Ten to thirteen weeks of chronic stress did not alter significantly the absolute ACTH and cortisol responses to the two peptides. In tethered pigs, the cortisol/ACTH ratio after CRH treatment, calculated from the area under the curve, was twofold that in loose-housed pigs. From these observations we conclude that after chronic stress the sensitivity of the adrenocortex to circulating ACTH was increased, whereas the sensitivity of the pituitary to CRH and/or LVP remained unaltered.
Frans A Helmond, Department of Human and Animal Physiology, Wageningen Agricultural University, Haarweg 10, 6709 PJ Wageningen, The Netherlands
Growth hormone (GH) modulates insulin-like growth factor I (IGF-I) and type I IGF receptor mRNA levels in the ovary of prepubertal GH-deficient rats
Authors: Malozowski Saul , Parmer Toni G , Trojan Sabina , Merriam George R , Gibori Geula , Roberts Charles T , LeRoith Derek , Werner Haim , Zilberstein Moshe 
Published: December 2008

Malozowski S, Parmer TG, Trojan S, Merriam GR, Gibori G, Roberts Jr CT, LeRoith D, Werner H, Zilberstein M. Growth hormone (GH) modulates insulin-like growth factor I (IGF-I) and type I IGF receptor mRNA levels in the ovary of prepubertal GH-deficient rats. Eur J Endocrinol 1995;132:497–501. ISSN 0804–4643
In order to explore the potential role of growth hormone (GH) in modulating insulin-like growth factor I (IGF-I) gene expression in the prepubertal rat ovary, female rats were rendered GH deficient by neonatal administration of monosodium glutamate (MSG). One group of rats received vehicle and served as the control. At 21 days of age, MSG-treated rats received either GH or vehicle for 2 weeks. On days 21, 24, 28 and 31 animals were weighed and subsets were sacrificed for liver RNA extraction. The remaining animals were sacrificed at day 35 when livers and ovaries were collected, and serum was obtained for GH determinations. The IGF-I mRNA levels were estimated by Northern blots and corroborated further by slot-blot analysis. The MSG-treated rats had lower body weights (p < 0.01) and GH levels (p < 0.05) than controls. Growth hormone replacement significantly accelerated the weight gain of MSG-treated rats. At day 24 and thereafter, three RNA IGF-I species (7.5, 1.8 and 0.8–1.2 kB) were seen in the liver. In the ovary, at age 35 days, two major IGF-I mRNA species (7.5 and 0.8–1.2kb) were seen. The MSG treatment consistently reduced the levels of both IGF-I mRNA species in the ovary. Growth hormone administration partially restored their expression, both in the liver and in the ovary. In addition, ovarian type I IGF receptor mRNA levels were increased in the MSG-treated rats when compared to controls. This trend was reversed by GH replacement. In summary, we have found that in prepubertal female rats rendered GH deficient with MSG, ovarian IGF-I gene expression is reduced while type I IGF receptor mRNA levels are increased. These findings are reversed with GH replacement. These results suggest a physiological role for GH in modulating IGF-I and type I IGF receptor genes in the ovary.
Saul Malozowski, FDA, HFD-510, Rockville, MD 20897, USA
Pituitary–ovarian dysfunction in rats with induced nephrotic syndrome
Authors: Menjívar Marta , Vilchis Felipe , Cárdenas Mario , Cruz Cristino , Merchant Horacio , Pérez-Palacios Gregorio , Pedraza-Chaverri José 
Published: December 2008

Menjívar M, Vilchis F, Cárdenas M, Cruz C, Merchant H, Pérez-Palacios G, Pedraza-Chaverri J. Pituitary–ovarian dysfunction in rats with induced nephrotic syndrome. Eur J Endocrinol 1995; 132:502–6. ISSN 0804–4643
The reproductive hormonal profile was evaluated in female rats with experimental nephrotic syndrome induced with a single subcutaneous dose of puromycin aminonucleoside (PAN). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), testosterone and 17β-estradiol (E2) were determined sequentially in control and experimental groups on days 1,3,7 and 10 after PAN administration. Prolactin levels were also assessed on day 10. In both groups, vaginal smears were taken daily throughout the study to evaluate cyclic histological changes. At the end of the experiment the histological appearance of the ovaries was evaluated by light microscopy. Nephrotic rats had a rapid loss of the estrous cycle starting on day 4, which set them at diestrus. At the same time the hormonal evaluation indicated a gradual decrease in E2, LH and P4 concentrations, starting from days 3, 7 and 10, respectively. No significant changes were noted in FSH or testosterone values. Besides, on day 10, prolactin concentrations remained unmodified. Even though most hormonal levels were found low on day 10, all values except E2 (undetectable) corresponded to the interval reported for the diestrus phase. Likewise, histological examination of ovarian tissue from nephrotic rats showed a considerable increase in the number of atretic follicles. These findings indicate that female rats with nephrotic syndrome develop an important endocrine dysfunction that probably involves steroidogenic tissues (ovary and/or adrenal gland), and suggest the existence of a hypothalamic–hypophyseal impairment.
Marta Menjívar, Department of Reproductive Biology, Instituto Nacional de la Nutrición Salvador Zubirán, Vasco de Quiroga N.15, Tlalpan 14000, México, D.F.
Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells
Authors: Brown Edward M , Pollak Martin , Hebert Steven C 
Published: December 2008

Brown EM, Pollak M, Hebert SC. Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells. Eur J Endocrinol 1995;132:523–31. ISSN 0804–4643
Mineral ion homeostasis in mammalian species is maintained by a complex mechanism comprising sensors of the extracellular calcium concentration (Ca02+) (i.e. parathyroid cells) as well as effectors that modify their translocation of mineral ions into and out of the extracellular fluid (e.g. kidney) in response to calciotropic hormones. Indirect evidence accumulated over the past decade suggested that parathyroid cells sense Ca02+ through a cell surface receptor coupled to intracellular second messenger systems via one or more guanine nucleotide regulatory (G) proteins. More recently, Brown et al. employed expression cloning in Xenopus laevis oocytes to isolate a cDNA encoding a Ca02+-sensing receptor from bovine parathyroid. The expressed receptor activates phospholipase C in a G-protein dependent manner and shows pharmacological properties almost identical to those of the native parathyroid receptor. Agonists for the receptor include not only divalent cations (e.g. Ca2+ and Mg2+) but also trivalent cations and even organic polycations such as neomycin. The deduced amino acid sequence of the cloned receptor confirms that it is a member of the superfamily of G-protein-coupled receptors. Receptor transcripts are present in parathyroid as well as in kidney, thyroid and brain. Therefore, this receptor may mediate the sensing of Ca02+ not only by parathyroid cells but also by other tissues directly regulated by Ca02+ (e.g. the thyroidal C cells and certain kidney cells) as well as those not currently known to be involved in calcium homeostasis (viz. in the brain). Further evidence for the physiological relevance of the receptor comes from the discovery that mutations in the human homolog of the Ca02+-sensing receptor gene cause three inherited disorders of mineral ion homeostasis. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are the clinical expression of inactivating mutations of the receptor when present in the heterozygous and homozygous state, respectively. An autosomal dominant form of hypocalcemia, on the other hand, results from an activating mutation of the receptor. Thus, this Ca02+-sensing receptor permits Ca02+ to act, in effect, as an extracellular first messenger in addition to its more widely recognized role as an intracellular second messenger.
Edward M Brown, Endocrine–Hypertension Division, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA02115, USA
Importance of the content and localization of tyrosine residues for thyroxine formation within the N-terminal part of human thyroglobulin
Authors: den Hartog Marcel T , Sijmons Carin C , Bakker Onno , Ris-Stalpers Carrie , de Vijlder Jan JM 
Published: December 2008

Den Hartog MT, Sijmons CC, Bakker 0, Ris-Stalpers C, de Vijlder JJM. Importance of the content and localization of tyrosine residues for thyroxine formation within the N-terminal part of human thyroglobulin. Eur J Endocrinol 1995;132:611–17. ISSN 0804–4643
Thyroxine (T4) is formed by coupling of iodinated tyrosine residues within thyroglobulin (TG). In mature TG, some iodinated tyrosine residues are involved preferentially in T4 formation. In order to investigate the specific role of various tyrosine residues in T4 formation, N-terminal TG fragments with mutated tyrosine residues were constructed. An N-terminal TG fragment 198 amino acids in size and containing seven tyrosine residues at amino acid positions 5, 29, 89, 97, 107, 130 and 192 was expressed in a baculovirus system. Using site-directed mutagenesis, eight mutant TG fragments were constructed in which different tyrosine residues were replaced by phenylalanine. In the first four TG mutants, one single tyrosine residue (5, 89, 97 or 130) was mutated. In the mutant Y(5,89,97,130)F all of these four tyrosine residues were replaced. The sixth mutant Y(29,89,107,130,192)F contained only tyrosine residues 5 and 97 and the seventh (Y(29,89,97,192)F) contained only tyrosine residues 5, 107 and 130. A TG fragment (Y(5,29,89,97,107,130,192)F) in which all tyrosine residues were replaced by phenylalanine was used as a negative control. After in vitro iodination with lactoperoxidase, specific T4 formation was established in the non-mutated wild-type N-terminal TG fragment. In general the T4 formation in the mutant TG constructs decreased when the total number of tyrosine residues in the 198 amino acid fragment decreased, except fragment Y(29,89,97,192) containing three tyrosine residues, two of them being 5 and 130. Although the rate of T4 formation in this mutated N-terminal TG fragment was lower, the ultimate T4 generation was the same as in the wild-type fragment. This indicates that a preferential involvement of tyrosines 5 and 130 in thyroid hormonogenesis may exist.
JJM de Vijlder, Academic Medical Center, University of Amsterdam, Children's Hospital "Emma Kinderziekenhuis/Het Kinder AMC", PO Box 22700, 1100 DE Amsterdam, The Netherlands
Thyroid hormones in fibrocystic breast disease
Authors: Martinez Luis , Castilla Jose A , Gil Teresa , Molina Jorge , Alarcón José L , Marcos Cristina , Herruzo Alfonso 
Published: December 2008

Martinez L, Castilla JA, Gil T, Molina J, Alarcón JL, Marcos C, Herruzo A. Thyroid hormones in fibrocystic breast disease. Eur J Endocrinol 1995;132:673–6. ISSN 0804–4643
This study was undertaken to evaluate the role of thyroid hormones in fibrocystic breast disease. The concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and free triiodothyronine (T3) were determined in serum of 50 women with fibrocystic breast disease without macrocysts (cysts of over 3 mm diameter) and in the serum and breast cyst fluid (BCF) of 60 women with fibrocystic breast disease and macrocysts. Possible relationships between thyroid hormones and estradiol, dehydroepiandrosterone sulfate, testosterone, progesterone and 17-hydroxyprogesterone in the BCF also were analyzed. Serum thyroid hormone levels did not differ between the two groups. Free T3 levels were higher in BCF than in serum (p < 0.001), whereas T4, free T4 and TSH concentrations were lower in BCF as compared to serum (p < 0.001). Cysts were divided according to their K+/Na+ ratio because a ratio above 3 represents a predictor of malignant transformation. Free T3 concentrations were higher in BCF than in serum, in both low K+/Na+ cysts and in cysts with a K+/ Na+ ratio above 3; those cysts with a high K+/Na+ ratio had the highest free T3 concentration. Free T3 in cysts correlated positively to the K+/Na+ ratio (r = 0.831; p < 0.001). Multiple linear regression analysis demonstrated that the concentration of free T3 in BCF was predicted statistically by the positive regression coefficient for the estradiol concentration. No candidate variable was included in the model to predict concentrations of TSH, free T4 or T4 in BCF. These data suggest an important role of free T3 in the physiology of fibrocystic breast disease.
Alfonso Herruzo, Departamento de Obstetricia y Ginecología, Hospital Regional "Virgen de las Nieves", 18014 Granada, Spain
Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery
Authors: Ross RJM , Chew SL , Perry L , Erskine K , Medbak S , Afshar F 
Published: December 2008

Ross RJM, Chew SL, Perry L, Erskine K, Medbak S, Afshar F. Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery. Eur J Endocrinol 1995;132:722–6. ISSN 0804–4643
The diagnosis of Cushing's Disease during pregnancy is complex because the biochemical features are obscured by changes in the normal hypothalamo-pituitary-adrenal axis that occur during gestation. To date, treatment has not been successful and there is a high incidence of maternal and fetal complications. We report the case of a 24-year-old woman with Cushing's disease who presented during her 16th week of pregnancy. Diagnosis was confirmed by the finding of elevated serum and urinary free cortisol levels with loss of the normal circadian rhythm of serum cortisol. Cortisol levels failed to suppress after a low-dose dexamethasone test but suppressed after a high-dose test. There was an exaggerated serum cortisol and plasma adrenocorticotrophin (ACTH) response to corticotrophinreleasing hormone (CRH). Magnetic resonance (MR) scanning demonstrated a pituitary tumour and cure was effected by transsphenoidal surgery where tumour immunostaining for ACTH was removed. Postoperatively the patient made an uncomplicated recovery; serum cortisol and plasma ACTH levels were undetectable at 9 days following surgery and recovery of the hypothalamo-pituitary axis occurred at 99 days after surgery. Caesarean section was performed at 38 weeks of pregnancy and a healthy but small female infant was delivered. This case illustrates the biochemical features of Cushing's disease during pregnancy and is the first report of the use of CRH testing and MR scanning in this clinical situation. The cure by surgery and successful outcome for mother and infant, with preservation of normal anterior pituitary function, suggest that transsphenoidal surgery may be the treatment of choice.
RJM Ross, Dept of Endocrinology, St Bartholomew's Hospital, London ECIA 7BE, UK
δ-Iodolactones decrease epidermal growth factor-induced proliferation and inositol-1,4,5-trisphosphate generation in porcine thyroid follicles—a possible mechanism of growth inhibition by iodide
Authors: Dugrillon Alex , Gärtner Roland 
Published: December 2008

Dugrillon A, Gärtner R. δIodolactones decrease epidermal growth factor-induced proliferation and inositol-1,4,5-trisphosphate generation in porcine thyroid follicles–a possible mechanism of growth inhibition by iodide. Eur J Endocrinol 1995;132:735–43. ISSN 0804–4643
δ-Iodolactones (6-iodo-8,11,14-eicosatrienoic δ-lactone, δ-IL), an iodinated derivative of arachidonic acid, has been shown to be synthesized in thyroid tissue and to inhibit thyroid cell proliferation. It is discussed as a potential mediator of the autoregulatory pathway of iodide in cyclic adenosine-3′,5′-monophosphate (cAMP)- and thyrotropin (TSH)-independent growth. We therefore further localized the action of iodide and of δ-IL in isolated porcine thyroid follicles. Epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) dose dependently stimulated thyroid cell proliferation which could be inhibited by staurosporin (0.1–10 nmol/l), Iodide (2.5–40 μmol/l) as well as δ-IL (0.5–2 μmol/l) also dose dependently inhibited EGF- and TPA-induced proliferation. As the calcium ionophor A23187 (100 pmol/l) completely abolished the inhibitory effects of iodide and of δ-IL, this may indicate a mechanism of δ-IL at or proximal to the calcium-dependent activation of protein kinase C. The growth inhibitory effect was restricted to δ-iodolactones when δ-Il was compared to 6-iodo-8,11,14,17-eicosatetraenoic δ-lactone and 5-iodo-7,10,13,16,19-docosapentaenoic γ-lactone, It could not be prevented with propylthiouracil and therefore deiodination and a different iodide action is unlikely. Inositol-1,4,5-trisphosphate (IP3) and cAMP were measured in extracts from isolated porcine thyroid follicles stimulated with EGF 10 ng/ml) or TSH 1.0U/l) revealing comparable kinetics in IP3 generation, while cAMP formation was only stimulated by TSH, δ-Iodolactone (2 μmol/l) only decreased EGF-induced IP3 formation, whereas TSH-induced IP3 and cAMP formation was unchanged. The γ-iodolactone which did not inhibit thyroid cell proliferation, also had no effect on IP 3 generation. These results demonstrate an action of iodide and δ-IL at the calcium-dependent signal transduction modulating thyroid cell proliferation by EGF but not TSH. δ-Iodolactone acts at or proximal to the generation of IP3 induced by EGF, whereas the TSH-dependent signal transduction seems to be unaltered. δ-Iodolactone may therefore be speculated as a specific inhibitory mediator of iodide on growth factor-induced thyroid cell proliferation.
Alex Dugrillon, Zentrallabor der Medizinischen Klinik und Poliklinik, University of Heidelberg, Bergheimer Str. 58, D-69115 Heidelberg. Germany
Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide
Authors: Boari Andrea , Barreca Antonina , Bestetti Gilberto E , Minuto Francesco , Venturoli Massimiliano 
Published: December 2008

Boari A, Barreca A, Bestetti GE, Minuto F, Venturoli M. Hypoglycemia in a dog with a leiomyoma of the gastric wall producing an insulin-like growth factor II-like peptide. Eur J Endocrinol 1995;132:744–50. ISSN 0804–4643
A 12-year-old mixed-breed male dog was referred to the Clinica Medica Veterinaria of Bologna University for recurrent episodes of seizures due to hypoglycemia with abnormally low plasma insulin levels (18 pmol/l), Resection of a large leiomyoma (780 g) of the gastric wall resulted in a permanent resolution of the hypoglycemic episodes. Insulin-like growth factors I and II (IGF-I and -II) were measured by RIA in serum before and after surgery and in tumor tissue. Results were compared to the serum concentration of 54 normal and to the tissue concentration observed in eight non-hypoglycemic dog gastric wall extracts. Before surgery, circulating immunoreactive IGF-I was 0.92 nmol/l, which is significantly lower than the control values (16.92 ± 8.44 nmol/l, range 3.53–35.03), while IGF-II was 152 nmol/l, which is significantly higher than the control values (42.21 ± 3.75. range 31.99–50.74). After surgery, IGF-I increased to 6.80 nmol/l while IGF-II decreased to 45.52 nmol/l, Tumor tissue IGF-II concentration was higher than normal (5.66 nmol/kg tissue as compared to a range in normal gastric wall tissue of 1.14–3.72 nmol/kg), while IGF-I was 0.08 nmol/kg tissue, which is close to the lowest normal value (range in controls, 0.08–1.18 nmol/kg). Partial characterization of IGF-II immunoreactivity extracted from tissue evidenced a molecular weight similar to that of mature IGF-II thus excluding that peptide released by the tumor is a precursor molecule. In agreement with these data, at variance with samples of normal dog gastric wall, IGF-II immunostaining was positive and in situ hybridization evidenced the expression of IGF-II mRNA in tumor tissue specimen. Evaluation of the molecular distribution of the IGFs in the circulation evidenced that IGF-II immunoreactivity was predominantly in the 3 5–65 kD region and barely detectable in the other regions. These results show that in dog, non-islet cell tumor hypoglycemia, as demonstrated in humans, can be ascribed to overproduction of IGF-II circulating in a molecular form that can more easily cross the capillary wall, thus exerting its insulin-like effects on target tissues.
Andrea Boari, Istituto di Clinica Medical Veterinaria di Bologna, Via Tolara di Sopra, 40064 Ozzano Emilia (BO), Italy