bluuebunny/crossref_metadata_2025 huggingface dataset:
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
Delayed puberty in males with β-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids
Authors: Valenti Sandra , Giusti Massimo , McGuinness Dorothy , Guido Roberta , Mori Pier Giorgio , Giordano Giulio , Dahl Kristine Diane
Published: December 2008

Valenti S, Giusti M, McGuinness D, Guido R, Mori PG, Giordano G, Dahl KD. Delayed puberty in males with β-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids. Eur J Endocrinol 1995;133:48–56. ISSN 0804–4643

Patients with β-thalassemia major often have pubertal delay, the etiology of which has not been fully elucidated. We investigated the pituitary–gonadal response to short-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five young males (aged 13.6–19.0 years) affected by β-thalassemia major and presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin levels were determined and their isoform profiles were examined, before and after GnRH treatment, in a pool of samples collected every 15 min for 240 min. Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepian-drosterone and 17 β-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5 and 7 of treatment. Five patients (aged 16.9–26.8 years) with confirmed diagnosis of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH therapy were also studied in the same protocol. Increased sex steroid levels were observed in both groups as a result of treatment. On day 7, the thalassemic patients had increased bioactive luteinizing hormone (LH) and follide-stimulating hormone (FSH), although immunoreactive LH and FSH were comparable to day 0. Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were noted in LH profiles on day 7. Similar results were observed in hypogonadal patients, who also had increased immunoreactive LH and FSH values. We suggest that the early stage of delayed puberty in thalassemia might be characterized by a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release, which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment seems to re-establish partially the correct pituitary–gonadal function.

Sandra Valenti, Department of Endocrinology and Metabolism, 6 Viale Benedetto XV, 16132 Genoa, Italy
Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism
Authors: Contempre Bernard , Dumont Jacques E , Denel Jean-François , Many Marie-Christine
Published: December 2008

Contempre B, Dumont JE, Denef J-F, Many M-C. Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism. Eur J Endocrinol 1995;133:99–109. ISSN 0804–4643

It has been suggested that selenium deficiency is a co-factor to iodine deficiency in the pathogenesis of myxoedematous cretinism. The mechanism proposed is that the generation of hydrogen peroxide is greatly increased in iodine-deficient thyroid glands, and that selenium is involved in the control of hydrogen peroxide and its derived free radicals. This study was carried out to investigate the effect of the possibly impaired cellular defence mechanism associated with selenium deficiency on thyroid necrosis and tissue repair. For this purpose, we studied thyroid tissue from selenium- (SE–) and/or iodine-deficient (I–) rats before and after an acute toxic iodine overload. In I– thyroids, necrotic cells were numerous. Acute iodine administration increased this effect. Necrosis was associated with transient infiltration of inflammatory cells. In 1–SE+ thyroids the tissue resumed its normal appearance. In 1–SE– thyroid glands, the iodide toxicity was stronger, with greater necrosis and inflammatory reaction. The inflammation resolved but was replaced by fibrotic tissue. Fifteen days after the toxic overload, the connective tissue volume was twice the control value. Before iodide overload, the proportion of dividing cells was equal in 1–SE+ and 1–SE– thyroids. Three days after the iodide overload, this proportion was increased in 1–SE+ thyroids but reduced in the 1–SE– thyroids. Overall, the 1–SE– thyroids had four times fewer dividing cells than the 1–SE+ thyroids. In summary, selenium deficiency coupled to iodine deficiency increased necrosis, induced fibrosis and impeded compensatory epithelial cell proliferation. These results are compatible with histological and functional descriptions of thyroid tissue from myxoedematous cretins.

B Contempre, IRIBHN, C.P. 602, Free University of Brussels, Medicine Faculty, 808 route de Lennik, B-1070 Brussels, Belgium
Comparative effects of food restriction, fasting, diabetes and thyroidectomy on growth hormone and thyrotropin gene expression in the rat pituitary
Authors: Rodriguez Manuela , Rodriguez Felipe , Jolin Trinidad , Santisteban Pilar
Published: December 2008

Rodriguez M, Rodriguez F, Jolin T, Santisteban P. Comparative effects of food restriction, fasting, diabetes and thyroidectomy on growth hormone and thyrotropin gene expression in the rat pituitary. Eur J Endocrinol 1995;133:110–6. ISSN 0804–4643

To examine the molecular basis for the decreased pituitary growth hormone (GH) and thyrotropin (TSH) content during restricted feeding, fasting and diabetes, we measured steady-state levels of mRNA for TSH-α TSH-β and GH in the pituitary from normal rats either fed ad libitum (C), limited to 75%, 50% and 25% (FR75, FR50, FR25, respectively) of ad libitum intake, or deprived of food for 2 and 4 days (F2 and F4, respectively), and also in streptozotocin-diabetic (D) and D insulin-treated animals. The results from these experimental groups were compared with those in thyroidectomized (Tx) rats. Pituitary mRNA was quantified by Northern blot hybridization with cDNA probes specific for rat TSH-α, TSH-β and GH. Although changes in the pituitary GH mRNA during restricted feeding, fasting and diabetes were similar qualitatively to those induced by hypothyroidism, GH mRNA levels in Tx rats (> 10% of C values) were less than in the other experimental groups (p < 0.001). Pituitaries from FR50, FR25 and D rats also contained less GH mRNA than F2 and F4 animals (p < 0.05). Thyroidectomy resulted in a marked increase in both TSH-β and TSH-α mRNAs, the changes in TSH-β mRNA being greater than those in TSH-α mRNA. In contrast, FR50, FR2 5, F2, F4 and D rats exhibited a decrease in pituitary TSH-β mRNA (60%, 50%, 35%, 36% and 33%, respectively, of C values; p < 0.01–0.05) and in TSH-α mRNA levels (81%, 64%, 46%, 43% and 36%, respectively, of normal values; p < 0.02–0.05), TSH-β mRNA showing the greater changes. However, pituitaries from F2, F4 and D rats contained less TSH-β and TSH-α mRNA levels than FR50 and FR25 animals (p < 0.05). Insulin therapy partially restored the changes in mRNA for GH, TSH-β and TSH-α observed in D rats. In addition, the pituitary nuclear triiodothyronine in Tx, FR50, FR25, F2, F4 and D rats was reduced to 19%, 73%, 52%, 76%, 51% and 41%, respectively of C values (p < 0.05–0.001). These data suggest that GH, TSH-α and TSH-β gene expression are modulated by metabolic and/or endocrine changes accompanying restricted feeding, fasting and diabetes.

P Santisteban, Instituto de Investigaciones Biomédicas, CSIC, Arturo Duperier 4, 28029 Madrid, Spain
Effects of V1- and V2-vasopressin (AVP) antagonists on the pressor, AVP and atrial natriuretic peptide responses to a hypertonic saline infusion in conscious anephric rats
Authors: Ota Kozo , Kimura Tokihisa , Inoue Minoru , Funyu Takeharu , Shoji Masaru , Sato Kazutoshi , Ohta Masahiro , Yamamoto Tadasu , Abe Keishi
Published: December 2008

Ota K, Kimura T, Inoue M, Funyu T, Shoji M, Sato K, Ohta M, Yamamoto T, Abe K, Effects of V1- and V2-vasopressin (AVP) antagonists on the pressor, AVP and atrial natriuretic peptide responses to a hypertonic saline infusion in conscious anephric rats. Eur J Endocrinol 1995;133:127–32. ISSN 0804–4643

To examine the role of vasopressin (AVP) receptors in the regulation of the hemodynamics and release of atrial natriuretic peptide (ANP), and the participation of renal nerve inputs in the osmotic AVP release, hypertonic saline (HS) was infused into conscious, bilaterally nephrectomized rats with nonpeptide, selective antagonists for the V1-receptor or V2-receptor of AVP. In the control group, HS alone increased mean arterial pressure, plasma ANP and AVP, plasma volume and plasma osmolality, and decreased the heart rate. In the V1-receptor antagonist group, an increase in the mean arterial pressure and a decrease in heart rate were completely abolished and an increase in plasma ANP was attenuated. In the V2-receptor antagonist group, increases in mean arterial pressure and plasma ANP and a decrease in heart rate were attenuated. However, the ratio of the changes in heart rate to the changes in mean arterial pressure in the V2-receptor antagonist group is significantly higher than that in the control group. In both experimental groups, increases in plasma AVP, plasma volume and plasma osmolality were not different from those in the control group. These results suggest that a HS-induced increase in mean arterial pressure is mediated by the pressor effect of AVP, mainly through V1-receptors, and that the depressor effect of AVP through V2-receptors may not influence tonically HS-induced hypertension. Moreover, HS-induced increase in plasma ANP is mediated mainly by increases in plasma volume and blood pressure, but may not be affected by a direct action of AVP to the heart. Renal afferent nerve inputs may not have effects on the regulation of osmotic AVP release.

Kozo Ota, Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-77, Japan
Plasma brain natriuretic peptide concentrations in healthy children from birth to adolescence: marked and rapid increase after birth
Authors: Yoshibayashi Muneo , Kamiya Tetsuro , Saito Yoshihiko , Nakao Kazuwa , Nishioka Kenya , Temma Shinji , Itoh Hiroaki , Shirakami Gotaro , Matsuo Hisayuki
Published: December 2008

Yoshibayashi M, Kamiya T. Saito Y. Nakao K, Nishioka K, Temma S, Itoh H, Shirakami G, Matsuo H. Plasma brain natriuretic peptide concentrations in healthy children from birth to adolescence: marked and rapid increase after birth. Eur J Endocrinol 1995;133:207–9. ISSN 0804–4643

The aim of the present study is to establish the normal range and to determine the developmental changes of plasma brain natriuretic peptide (BNP) concentrations in children. We measured plasma BNP concentrations as well as atrial natriuretic peptide (ANP) concentrations in 58 healthy children from birth to adolescence and in the umbilical vein of 20 healthy neonates using highly sensitive immunoradiometric assays. The plasma BNP concentration was the highest at 0 days of age and descended through maturation to be almost constant and to be at the adult level at 3 months of age. The plasma BNP concentration at 0 days of age (56.7 ± 49.6 fmol/ml; mean±sd) was 25 to 30 times higher than the adult level and 21 times higher than that in the umbilical vein (2.7 ± 1.4fmol/ml), The plasma ANP concentration at 0 days of age was not significantly different from that in the umbilical vein. The ratio of BNP to ANP was also the highest at 0 days of age (1.39 ± 0.72) and decreased through maturation to be at the adult level at 3 months of age. Thus, the plasma BNP concentration in healthy subjects showed a marked, rapid and preferential increase immediately after birth, suggesting that BNP has a physiological role distinct from that of ANP in the perinatal circulatory changes from fetus to neonate.

Muneo Yoshibayashi, Department of Pediatrics, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565, Japan
Insulin-like growth factor I does not inhibit insulin secretion in adult human pancreatic islets in tissue culture
Authors: Eizirik Décio L , Skottner Anna , Hellerström Claes
Published: December 2008

Eizirik DL, Skottner A, Hellerström C. Insulin-like growth factor I does not inhibit insulin secretion in adult human pancreatic islets in tissue culture. Eur J Endocrinol 1995;133:248–50. ISSN 0804–4643

Insulin-like growth factor I (IGF-I) has been found to increase insulin sensitivity and suppress insulin secretion, thereby having a potential interest as a therapeutic agent for non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to investigate the direct actions of IGF-I (400 ng/ml) on human pancreatic islets, or on rat pancreatic islets, during a 48 h period in tissue culture. Insulin-like growth factor I did not affect medium insulin accumulation, DNA or insulin content or short-term glucose-induced insulin release of human islets. However, in rat islets the peptide induced a significant decrease in the insulin increase ratio in response to 16.7 mmol/l glucose. In conclusion, the present data suggest that IGF-I does not directly affect the function of human pancreatic β-cells If this in vitro data can be extrapolated to the in vivo situation, it suggests that the observed inhibitory effects of IGF-I on serum insulin levels may be secondary to peripheral effects of the peptide.

Décio L Eizirik, Department of Medical Cell Biology, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden
Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures
Authors: Calogero Aldo E , Bagdy Gyorgy , Burrello Nunziatina , Polosa Pietro , D'Agata Rosario
Published: December 2008

Calogero AE, Bagdy G, Burrello N, Polosa P. D'Agata R. Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures. Eur J Endocrinol 1995;133:251–4. ISSN 0804–4643

Although several serotonin (5-HT) receptor types have been shown capable of stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, relatively little is known about the role of the 5-HT3 receptor, a receptor that has generated a great deal of interest for its involvement in many behavioral and therapeutic effects. Hence, in this study, we tested the effects of the 5-HT¾ receptor antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) and the selective 5-HT3 receptor antagonist 3-tropanyl-3,5-dichlorobenzoate (MDL 72222) on ACTH release stimulated by 5-HT from primary cultures of rat pituitary cells. Subsequently, we evaluated the effects of the selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG) on basal, corticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-stimulated ACTH release. The maximal stimulatory effect of 5-HT (10−9 mol/l on ACTH release was antagonized by both ICS 205-930 and MDL 72222, suggesting that 5-HT stimulates basal ACTH release through activation of 5-HT3 receptors. Accordingly, m-CPBG stimulated basal ACTH release in a concentration-dependent fashion. In contrast to 5-HT, m-CPBG did not have any effect on CRH-stimulated ACTH release and inhibited AVP-stimulated ACTH release in a concentration-dependent manner. These data suggest that the 5-HT3 receptor is involved in the release of ACTH from the pituitary gland in vitro.

Aldo E Calogero, Istituto di Clinica Medica I, Ospedale Garibaldi, Piazza S Maria di Gesú, 95123 Catania, Italy
Effect of restraint stress on the preovulatory luteinizing hormone profile and ovulation in the rat
Authors: Roozendaal Marjolijn M , Swarts Hans JM , Wiegant Victor M , Mattheij John AM
Published: December 2008

Roozendaal MM, Swarts HJM, Wiegant VM, Mattheij JAM. Effect of restraint stress on the preovulatory luteinizing hormone profile and ovulation in the rat. Eur J Endocrinol 1995;133:347–53. ISSN 0804–4643

Plasma profiles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured during restraint stress on the day of pro-oestrus; these profiles were considered in relation to ovulation rate on the next day. Rats bearing a permanent jugular vein cannula were subjected to restraint, which was started 0, 1 or 2 h before the presumed onset of the LH surge and ended just before the beginning of the dark period. Exposure to restraint resulted in a suppression of the secretion of both gonadotrophins on the day of pro-oestrus. Suppression of the LH surge was virtually complete (plasma LH ≤ 0.2 ng/ml) in 15 out of 32 stressed rats, and the ovaries of these rats contained graafian follicles with oocytes in germinal vesicle stage. In these rats, the LH surge did not occur 24 h later. In the remaining 17 rats, restraint resulted in a considerable suppression of the LH surge. Of these rats, five had an ovulation rate of 100% and four ovulated partially. In unruptured follicles of the latter, the oocyte had not resumed meiosis and the follicle wall was not luteinized. In the remaining eight rats with a reduced LH surge, ovulations had not occurred and graafian follicles were unaffected. The results of this study indicate that during pro-oestrus restraint stress suppresses and does not delay the release of preovulatory gonadotrophins. Partial suppression of LH by restraint does not result in induction of meiotic resumption without subsequent ovulation or in luteinized unruptured follicles.

JAM Mattheij, Department of Human and Animal Physiology, Agricultural University, Haarweg 10, 6709 PJ, Wageningen, The Netherlands
Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats
Authors: Genazzani Andrea R , Palumbo Marco A , de Micheroux Antonio A , Artini Paolo G , Criscuolo Mario , Ficarra Guido , Guo Ai-Li , Benelli Augusta , Bertolini Alfio , Petraglia Felice , Purdy Robert H
Published: December 2008

Genazzani AR, Palumbo MA, de Micheroux AA, Artini PG, Criscuolo M, Ficarra G, Guo A-L, Benelli A, Bertolini A, Petraglia E. Purdy RH. Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats. Eur J Endocrinol 1995;133:375–80. ISSN 0804–4643

The present study investigated the effect of allopregnanolone (5α-pregnan-3α-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on highpressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.

AR Genazzani, Institute of Obstetrics and Gynecology, University of Pisa, via Roma 67, 56100 Pisa, Italy
Effects of treatment with octreotide in acromegalic patients—a multicenter Italian study
Authors: Arosio Maura , Macchelli Sonia , Rossi Cristina M , Casati Giovanni , Biella Orietta , Faglia Giovanni
Published: December 2008

Arosio M, Macchelli S, Rossi CM, Casati G, Biella 0, Faglia G, the Italian Multicenter Octreotide Study Group. Effects of treatment with octreotide in acromegalic patients—a multicenter Italian study. Eur J Endocrinol 1995:133:430–9. ISSN 0804–4643

Treatment of acromegaly is effective in reversing the reduced life-span of patients only when serum growth hormone (GH) concentrations are lowered to less than 2.5 μg/l. Usual treatments achieve this goal in no more than 50–60% of patients. The effects of octreotide were studied in a prospective, open label study with 68 acromegalic patients enrolled in 10 Italian centers. Octreotide was administered sc at a dose of 100 μg t.i.d. for 1 year. After 3 months of therapy, octreotide was effective in decreasing serum GH levels below 2.5 μg/l in 16 out of 64 acromegalic patients (25%). Fifteen of them had pretreatment GH levels below 25 μg/l. Insulin-like growth factor I (IGF-I) levels normalized in about 40% of patients. No further GH reduction was observed after 1 year of treatment. The presence of abnormal GH responses to thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone was reduced from 54 to 24% and from 16 to 12%, respectively. Tumor shrinkage was observed in 50% of 26 non-irradiated patients after 12 months of treatment. Both basal and TRH-stimulated serum prolactin levels significantly decreased in the 11 hyperprolactinemic patients. Although serum thyrotropin, free triiodothyronine and free thyroxine concentrations were not modified, a significant reduction of thyrotropin response to TRH was observed in the 9th month of therapy. In non-diabetic patients, an increase of mean blood glucose levels without modifications of fasting morning concentrations was found. About one-quarter of the patients with overt diabetes mellitus had an impairment of their metabolic control. Main clinical symptoms of acromegaly improved in 70–80% of patients. An 18% decrease of low-density-lipoprotein cholesterol and unchanged high-densitylipoprotein cholesterol levels were observed in 35 patients studied. Triglyceride levels decreased in patients with hypertriglyceridemia pretreatment. Regarding side effects, gallstones were newly diagnosed in five patients, three patients dropped out because of severe diarrhea and two diabetic patients dropped out due to worsening of their metabolic control. In conclusion, octreotide is an effective treatment of acromegaly, mainly in patients with moderate elevation of serum GH levels. The drug has also been proved to positively affect dyslipidemia.

Maura Arosio, Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, Pad. Granelli, Via F Sforza 35, 20122 Milano, Italy
Signal transduction in rat myometrial cells: comparison of the actions of endothelin-1, oxytocin and prostaglandin F2α
Authors: Molnár Miklós , Hertelendy Frank
Published: December 2008

Molnár M, Hertelendy F. Signal transduction in rat myometrial cells: comparison of the actions of endothelin-1, oxytocin and prostaglandin F2α. Eur J Endocrinol 1995;133:467–74. ISSN 0804–4643

The objectives of this study were to evaluate and compare the actions of endothelin-1 (ET-1), oxytocin, prostaglandin F2α (PGF2α) and inositol 1,4,5-trisphosphate (IP3) on Ca2+ mobilization in permeabilized rat myometrial cells and to examine the activation of the inositol lipid cycle in intact myocytes. Cells were isolated from late pregnant rat myometrium and used as confluent monolayers after a single passage. All four agonists caused a biphasic release of45Ca2+ from non-mitochondrial pool(s), with the rank order of potency: oxytocin > PGF2α > ET-1 > IP3. Inhibitors of phospholipase C blocked ET-1-and oxytocin-promoted but not PGF2α-promoted 45Ca2+ efflux. Similarly, heparin, an IP3 receptor blocker, failed to inhibit PGF2α-induced Ca2+ release while inhibiting the action of the other agonists. Endothelin-1 and oxytocin stimulated inositol phosphate accumulation at concentrations similar to those that promoted 45Ca2+ efflux, whereas about 100 times higher concentrations of PGF2α were needed to activate this signaling pathway in intact cells. It is concluded that the primary action of PGF2α in myometrial cells is to enhance Ca2+ influx, whereas oxytocin and ET-1 receptors are coupled to phospholipase C, generating IP3 and raising the intracellular concentration of free Ca2+ from intracellular as well as extracellular sources.

Frank Hertelendy, Dept. Ob/Gyn, St Loufis University Health Sciences Center, 3635 Vista Ave at Grand Blvd, St Louis, MO 63110-0250, USA