bluuebunny/crossref_metadata_2025_split huggingface dataset:
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
Underfeeding of rat mothers during the first two trimesters of gestation does not alter insulin action and insulin secretion in the progeny
Authors: Portha Bernard , Kergoat Micheline , Blondel Olivier , Bailbe Danielle 
Published: December 2008

Portha B, Kergoat M, Blondel 0, Bailbe D. Underfeeding of rat mothers during the first two trimesters of gestation does not alter insulin action and insulin secretion in the progeny. Eur J Endocrinol 1995;133:475–82. ISSN 0804–4643
It has been suggested that impaired insulin action and/or insulin secretion in adult mammals could be a consequence of severe food restriction during fetal life. We have determined to what extent glucose homeostasis and insulin action are modified in male offspring of rats undernourished only during the first two trimesters of pregnancy. Pregnant females then were assigned to one of the following three experimental conditions. Rats in the first group had their food restricted to 50% of their pregnancy intake during the first 2 weeks of pregnancy, after which they were allowed to eat ad libitum. Rats in the second group were similarly restricted during the first 2 weeks, but beginning on day 14 of gestation were pair-fed to control rats until weaning on day 21 after birth. Such an experimental group was introduced because we observed that food-restricted mothers increased their food intake significantly above control levels in the last week of gestation and maintained this increase into the first postnatal week, when they were returned to ad libitum feeding on day 14 of gestation. Control rats (third group) were given access to food ad libitum throughout pregnancy and lactation. Offspring of mothers in the three groups are referred to as food-restricted/ad libitum refed (RA), food-restricted/ pair-refed (RP) and control (C) groups, respectively. From 6 weeks of age, RA males ate significantly more food and gained significantly more weight on a standard laboratory diet than control offspring. Maternal overeating after the restriction appears to be a necessary component in the aetiology of these effects because pair-refeeding mothers blocked the subsequent hyperphagia of male offspring fed the stock diet (RP group). In both the RA and RP groups, basal plasma glucose and insulin levels were not significantly different from those in control offspring and no alteration of the tolerance to intravenous glucose and the in vivo insulin secretory response to glucose was detected. Moreover, glucose utilization and endogenous glucose production were not impaired when measured either in the basal situation (postabsorptive state) or in hyperinsulinaemic conditions. Therefore, early food restriction of the mothers exerts no adverse effect upon insulin secretion and insulin action in the male offspring.
B Portha, Lab. Physiopathology of Nutrition, CNRS URA 307, Université D. Diderot, Paris 7, 2 place Jussieu, Tour 33, 75251 Paris Cedex 05, France
Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas
Authors: Luts Lena , Bergenfelz Anders , Alumets Jan , Sundler Frank 
Published: December 2008

Luts L, Bergenfelz A, Alumets J, Sundler F. Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas. Eur J Endocrinol 1995;133:543–51. ISSN 0804–4643
There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SPand VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.
Lena Luts, Department of Medical Cell Research, Biskopsgatan 5, S-223 62 Lund, Sweden
Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines
Authors: Tang Pei-Zhong , Gannon Michael J , Andrew Alison , Miller David 
Published: December 2008

Tang P-Z, Gannon MJ, Andrew A, Miller D. Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines. Eur J Endocrinol 1995;133:598–605. ISSN 0804–4643
Gene amplification with target-specific primers (reverse-transcription polymerase chain reaction (RTPCR)) was used to monitor the relative expression of oestrogen and progesterone receptor mRNAs alongside the mRNAs for heat shock proteins HSP 90α, HSP 90β and HSP 70a in normal samples of human endometrial tissue over the whole menstrual cycle and in short-term cultures of steroidresponsive (T47-D) and unresponsive (HRT-18) cell lines exposed to oestradiol and progesterone over a 24-h incubation period. In endometrium, oestrogen and progesterone receptors followed the expected patterns of expression at the protein level during the menstrual cycle and also showed a positive correlation of expression with each other throughout (r = 0.514). Of the HSPs only HSP 90α expression correlated positively with oestrogen receptor (r = 0.687), while HSP 70a expression, which peaked in the late secretory stage, displayed a significantly inverse correlation with HSP 90β expression (r = −0.526). All p values < 0.05. In T47-D cell cultures, oestrogen receptor expression was stimulated transiently by oestradiol (10−7 mol/l) and more persistently by progesterone (10−7 mol/l). Progesterone receptor expression was depressed by progesterone and weakly stimulated by oestradiol. HSP 70a and HSP 90α expression were stimulated by oestradiol. Progesterone generally depressed HSP 90α expression and simultaneous addition of both oestradiol and progesterone to the culture medium was antagonistic to HSP 90α expression. No clear effect of agonist addition on HSP mRNA expression was apparent in the HRT-18 cultures. A possible mechanism for observed oestrogenic effects on HSP expression is put forward.
David Miller, Institute of Pathology, Department of Clinical Medicine, Algernon Firth Building, University of Leeds, Leeds, LS2 9JT UK
Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with calcitriol—Effects of 22-oxacalcitriol on osteoclast-like cell formation and bone-resorbing activity
Authors: Kanatani Masanori , Sugimoto Toshitsugu , Kaji Hiroshi , Kano Junichi , Chihara Kazuo 
Published: December 2008

Kanatani M, Sugimoto T, Kaji H, Kano J, Chihara K. Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with calcitriol. Eur J Endocrinol 1995;133:618–25. ISSN 0804–4643
22-Oxacalcitriol (OCT), a synthetic vitamin D3 analog, can mimic the ability of calcitriol to differentiate leukemia and skin cells, to enhance the immune response and to suppress parathyroid hormone secretion, but has much less calcemic activity than that of calcitriol. The mechanism of this selective action remains not fully understood, and the actions of OCT on bone metabolism are little known. The present study was, therefore, designed to investigate the effects of OCT and calcitriol on: the proliferation and functions of osteoblastic MC3T3-E1 cells; osteoclast-like cell formation from hemopoietic blast cells in the absence of stromal cells as well as from unfractionated bone cells in the presence of stromal cells; bone resorption; and the proliferation of MC3T3-E1 cells via monocytes. 22-Oxacalcitriol and calcitriol inhibited [3H]thymidine (TdR) incorporation, alkaline phosphatase activity and collagen synthesis of MC3T3-E1 cells to a similar degree. Both OCT (10−10–10−8 mol/l) and calcitriol significantly and similarly stimulated osteoclast-like cell formation from both hemopoietic blast cells and unfractionated bone cells. 22-Oxacalcitriol (10−10 and 10−8 mol/l) significantly stimulated bone resorption, although to a slightly lesser degree than did calcitriol. Human monocyte-conditioned medium (CM) significantly stimulated TdR incorporation into MC3T3-E1 cells. On the other hand, CM obtained from monocytes treated with calcitriol (10−10–10−8 mol/l) significantly inhibited TdR incorporation in a dose-related fashion, whereas CM obtained from monocytes treated with OCT (10−10–10−8 mol/l) significantly stimulated TdR incorporation in a dose-related fashion. Thus, the actions of OCT on osteoblasts, osteoclast precursor cells and mature osteoclasts, possibly via osteoblasts, are mostly similar to those of calcitriol in vitro. The low activity of OCT in mobilizing calcium from bone in vivo, therefore, appears to be due to some other factor. OCT and calcitriol differed only in their indirect effects on the proliferation of osteoblasts via monocytes, possibly through modulating the release from monocytes of local factors that affect bone remodelling.
Toshitsugu Sugimoto, Third Division, Department of Medicine, Kobe University School of Medicine, Kobe, Japan
Effects of growth hormone and insulin-like growth factor I on the immune system
Authors: Auernhammer Christoph J , Strasburger Christian J 
Published: December 2008

Auernhammer CJ, Strasburger CJ. Effects of growth hormone and insulin-like growth factor I on the immune system. Eur J Endocrinol 1995;133:635–45. ISSN 0804–4643
Growth hormone-releasing hormone (GHRH). growth hormone (GH), prolactin (PRL) and insulin-like growth factor I (IGF-I) are synthesized and secreted by various immunocompetent cells. In addition, GHRH, GH, PRL and IGF-I receptors are expressed on immune cells. Growth hormone, PRL and IGF-I stimulate the proliferation of immunocompetent cells and modulate humoral and cellular immune functions, i.e. immunoglobuline secretion of B cells, thymulin secretion of thymic epithelial cells, natural killer cell activity, phagocytosis, oxidative burst and killing capacity of neutrophils and macrophages. No clinically significant cellular or humoral immunodeficiency has been found in GH-deficient patients. However, several immunological parameters and functions are altered in GH-deficient patients when compared to normal controls. The data available to date indicate that endocrine and pleiotropic para- and autocrine mechanisms of action are involved in a neuropeptide immune network, including GH PRL and IGF-I as modulators of immune function.
Christian J Strasburger, Medizinische Klinik, Klinikum Innenstadt der LMU, Ziemssenstr. 1, 80336 Munich, Germany
Growth hormone receptor: structure and signal transduction
Authors: Postel-Vinay Marie-Catherine , Finidori Joëlle 
Published: December 2008

Postel-Vinay M-C, Finidori J. Growth hormone receptor: structure and signal transduction. Eur J Endocrinol 1995;133:654–9. ISSN 0804–4643
The growth hormone receptor (GHR) belongs to the superfamily of transmembrane proteins that includes the prolactin receptor and a number of cytokine receptors. Two forms exist for the GHR: the full-length membrane-bound human receptor is a protein of 620 amino acids with a single transmembrane region; and the GH binding protein (GHBP) is a short soluble form corresponding to the extracellular domain of the full-length receptor. In rodents, GHBP is encoded by a specific mRNA of 1.2–1.5 kb, whereas in man and other species GHBP is believed to result from proteolytic cleavage of the membrane receptor. Growth hormone binding protein prolongs the half-life of GH but other functions for GHBP remain to be demonstrated. Recombinant GHBP complexed to human GH shows a 2:1 stoichiometric crystal structure. Growth hormone-induced dimerization of the cell surface GHR appears to be a prerequisite for biological activity of the hormone. JAK2 has been identified as a tyrosine kinase associated with GHR and other receptors of the superfamily. Binding of GH to its receptor results in dimerization of the GHR, phosphorylation of JAK2 and of the GHR. Other substrates for JAK2 have to be identified. Transcription factors belonging to the STAT (signal transducers and activators of transcriptions) family are involved in the transcriptional effects of GH. The activity of mutants of the GHR has been measured in functional tests to identify sequences of the cytoplasmic domain of the receptor that are important for signal transduction. A proline-rich sequence, called Box I, conserved among members of the receptor family has been shown to be crucial for GH effects on gene transcription, MAP kinase activity and cell proliferation. The C-terminal region of the GHR is required for tyrosine phosphorylation of the receptor and for a hormonal effect on gene transcription, whereas only 46 membrane proximal amino acids of the cytoplasmic domain are necessary for activation of JAK2 and transduction of the GH proliferative signal. Much work remains to be done to identify other protein kinases and signalling molecules involved in the mechanism of action of GH.
M-C Postel-Vinay, INSERM Unité 344, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone
Authors: Allolio Bruno , Oremus Martin , Reincke Martin , Schaeffer Hans-Jörg , Winkelmann Werner , Heck Georg , Schulte Heinrich M 
Published: December 2008

Allolio B, Oremus M, Reincke M, Schaeffer H-J, Winkelmann W, Heck G, Schulte HM. High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone. Eur J Endocrinol 1995;133:696–700. ISSN 0804–4643
High concentrations of unbound cortisol in late pregnancy have been explained by the antiglucocorticoid activity of high progesterone levels. To further test this hypothesis we studied the effect of high-dose progesterone on baseline and corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a double-blind crossover study eight healthy male volunteers received either progesterone (0.714 mg · kg−1 · h−1 for 60 min followed by a dose of 0.45 mg · kg−1 · h−1 over a total infusion time of 315 min) or vehicle as a continuous intravenous infusion. At 210 min a CRH test (0.1 μg/kg body weight as bolus iv) was performed. Within 30 min after the start of progesterone administration the serum progesterone level increased to 454 ± 31 nmol/l and remained in the range of third trimester pregnancy concentrations throughout the infusion period. During vehicle infusion the progesterone level remained in the normal range for healthy males and demonstrated a small but significant increase after CRH (1.52 ± 0.23 vs 0.74 ± 0.14 nmol/l; p < 0.01). However, baseline and CRH-stimulated serum cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose progesterone. Moreover, unbound salivary cortisol also was not affected by progesterone, suggesting that there is no significant competition for transcortin binding sites. In conclusion, no antiglucorticoid activity was found after short-term administration of progesterone in males. These findings cast doubts on the concept that the alterations of the pituitary–adrenal axis in late pregnancy are induced by the antiglucocorticoid activity of high progesterone concentrations.
Bruno Allolio, Medizinische Universitätsklinik Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany
Effects of growth hormone overproduction on grip strength of transgenic mice
Authors: Wolf Eckhard , Wanke Rüdiger , Schenck Emanuel , Hermanns Walter , Brem Gottfried 
Published: December 2008

Wolf E, Wanke R, Schenck E, Hermanns W, Brem G. Effects of growth hormone overproduction on grip strength of transgenic mice. Eur J Endocrinol 1995;133:735–40. ISSN 0804–4643
Growth hormone (GH) is used by athletes like bodybuilders to increase muscle strength and weight gain. On the other hand, chronic hypersecretion of GH in active acromegaly may result in outwardly hypertrophied but functionally weaker muscles. As a model for studying long-term effects of GH on muscle strength, we analysed transgenic mice (TM) carrying rat phosphoenolpyruvate carboxykinasebovine GH (PEPCKbGH) fusion genes, which are expressed in liver and kidney but not in skeletal muscle. Circulating GH levels in TM ranged between 0.5 and 3 μg/ml, resulting in increased (p <0.001) body weight (wt) as well as increased (p <0.01) weights of forelimb and hindlimb muscles. However, muscle weight/body wt ratios of TM were 16–20% smaller than in controls (p<0.05), Forelimb grip strength of hemizygous TM (16 males, 132 ± 45 days old, body wt = 56.8 ± 8.3 g; 32 females, 146 ± 38 days old, body wt = 54.9 ± 6.1 g) and non-transgenic controls (28 males, 127 ± days old, body wt = 40.5±2.9 g; 33 females, 126 ±47 days old, body wt = 32.1 ± 3.6 g) was determined using an automated grip strength meter. Data were computed by analysis of variance, taking into account effects of group, sex and age. Least-squares means estimated for the grip strength (N) of male TM (1.91) and controls (1.92) were significantly (p<0.05) greater than those of female TM (1.78) and controls (1.61). A significant difference between groups was only seen in females (p <0.01). Least-squares means estimated for grip strength/body wt ratios (N/10 g) of male (0.34) and female TM (0.33) were 29% and 35% lower than those of male (0.48) and female controls (0.51), respectively (p <0.001). In summary, long-term elevated GH levels in TM increased muscle weight less efficiently than body weight, and muscle strength did not increase proportionally with muscle weight.
Eckhard Wolf, Lehrstuhl für Molekulare Tierzucht und Haustiergenetik, Ludwig-Maximilians-Universität München, Würmtalstraβe 221, 81375 München, Germany
Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog
Authors: Fanciulli Giuseppe , Oliva Osvaldo , Tomasi Paolo A , Pala Alessandra , Bertoncelli Alba , Dettori Alessandra , Delitala Giuseppe 
Published: December 2008

Fanciulli G, Oliva O, Tomasi PA. Pala A. Bertoncelli A, Dettori A, Delitala G. Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. Eur J Endocrinol 1996:134:73–6. ISSN 0804–4643
Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli: in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opioids induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline: (b) a met-enkephalin analog G-DAMME 250 μg IV as a bolus at time ′: (c) hGH 2 IU as an IV bolus at time −180′; (d) G-DAMME as above, preceded by hGH as above. In our study. G-DAMME stimulated GH secretion both basally (peak 17.9 ± 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 ± 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded.
Giuseppe Delitala, Chair of Endocrinology, Viale S. Pietro 12, University of Sassari, 07100 Sassari. Italy
Long-term GnRH-agonist administration revealed a GnRHindependent mechanism stimulating FSH discharge in humans
Authors: Genazzani Alessandro D , Massolo Fausta , Ferrari Elena , Gandolfi Andrea , Petraglia Felice , Genazzani Andrea R 
Published: December 2008

Genazzani AD. Massolo F. Ferrari E, Gandolfi A, Petraglia F, Genazzani AR. Long -term GnRH-agonist administration revealed a GnRH-independent mechanism stimulating FSH discharge in humans. Eur J Endorcrinol 1996:134:77–83. ISSN 0804–4643
The present study evaluated the FSH and LH episodic discharge in different physiopathological conditions undergoing chronic GnRH-agonist administration. Four girls with true precocious puberty and five postmenopausal women were administered GnRH-agonist (3.73 leuprolide acetate every 4 weeks: Takeda Italia, Rome, Italy) for at least 4 months. Plasma LH and FSH secretory profiles were assessed before and under GnRH-agonist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, with blood sampling intervals of 10 min. Pubertal and postmenopausal patients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration: this co-secretion disappeared in both groups after 21 and 120 days of treatment. Moreover, while LH concentrations decreased to almost undetectable levels and LH episodic release disappeared. FSH plasma levels were only partially reduced and FSH episodic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH but not FSH episodic release. These data enforce the hypothesis that FSH episodic discharge might be dependent not only on hypothalamic GnRH, but also on a GnRH-independent stimulatory pathway.
Alessandro D Genazzani, Department of Obstetrics and Gynecology, University of Modena, Via del Pozzo 71, 41100 Modena, Italy