bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of estrogen receptor-mediated gene transcription by IGF-I in human breast cancer cells
Authors: Lee A V , Weng C-N , Jackson J G , Yee D 
Published: December 2004

Abstract
Estrogen and IGF-I are potent mitogens for most breast cancer cell lines, and although their signaling pathways contrast, there is considerable interaction between them. Recent evidence indicating that IGF-I can alter estrogen receptor (ER) action led us to investigate whether an inhibitor of IGF-I action, IGF-binding protein-1 (IGFBP-1), could affect transcriptional activation of ER. First, we confirmed that tamoxifen (TAM) could inhibit IGF-I-mediated proliferation of MCF-7 cells. Although TAM can increase IGFBP-3 expression in MCF-7 cells, and this binding protein has been shown to be able to inhibit IGF action, TAM had no effect on IGF-I-stimulated tyrosine phosphorylation of IGF-I receptor or the downstream signaling molecule, insulin receptor substrate-1. Therefore, to confirm that IGF-I was affecting transcriptional activation of ER, we utilized a gene reporter assay using a single consensus estrogen response element (ERE-tk-luc) upstream ofluciferase. As expected, estradiol (E2; 1 nm) increased transcriptional activation three- to fivefold from the ERE in three ER-positive breast cancer cell lines (MCF-7, ZR-75 and T47D). A 2·5- to 4-fold increase was also seen with IGF-I (5 nm). TAM (1 μm) effectively blocked activation by E2 and IGF-I, indicating disruption of ER-mediated transcription. As expected, human recombinant IGFBP-1 (80 nm) completely inhibited IGF-I-mediated activation of ER, however, IGFBP-1 also caused a significant decrease in E2-mediated activation. We also noticed that IGF-I increased the activity of all plasmids that we cotransfected including TATA-luc, SV40-luc and pGLBasic. This effect was post-transcriptional, as it was not affected by actinomycin D (2 μg/ml), while we were able to completely inhibit E2-mediated transcriptional activation of ERE-tk-luc. Unlike the complete inhibition of ER-mediated transcriptional activation by actinomycin D, IGF-I-mediated transactivation was reduced by only 50%, indicating that the activation by IGF-I represented both transcriptional and post-transcriptional effects. This study confirmed that IGF-I can cause transcriptional activation of endogenous ER in human breast cancer cells, and inhibition of ER action by IGFBP-1 suggests that IGF-I signaling may be necessary for maximal ER activation.
Journal of Endocrinology (1997) 152, 39–47
Characterization of insulin glycation in insulin-secreting cells maintained in tissue culture
Authors: Abdel-Wahab Y H A , O'Harte F P M , Barnett C R , Flatt P R 
Published: December 2004

Abstract
Characteristics of cellular insulin glycation were examined in the pancreatic B-cell line, BRIN-BD11. The extent of insulin glycation increased stepwise during 72 h of culture at 5·6–33·3 mmol/l glucose, attaining levels up to 27%. Glycation of insulin at 33·3 mmol/l glucose was rapid, reaching maximal values within 2 h, and not readily reversible during 2 to 24 h of subsequent exposure to 5·6 mmol/l glucose. Glycated insulin was readily secreted by BRIN-BD11 cells upon active stimulation with glucose and other secretagogues. Cellular insulin glycation was decreased by 66–80% by inhibitors of protein glycation, vitamin C, aminoguanidine or acetylsalicylic acid. Modulation of insulin-secretory activity of BRIN-BD11 cells by co-culture at high glucose with diazoxide, l-alanine or glibenclamide indicated that long-term stimulation of secretion was associated with a decrease in the extent of insulin glycation. Glycation of insulin in vitro was substantially less extensive than in BRIN-BD11 cells, although glucose-6-phosphate and glyceraldehyde-3-phosphate were 1·4- to 2·0-fold more reactive than glucose per se. These observations indicate that insulin is readily glycated and secreted from insulin-secreting cells under hyperglycaemic conditions in culture.
Journal of Endocrinology (1997) 152, 59–67
Rapid changes in heteronuclear RNA for corticotrophin-releasing hormone and arginine vasopressin in response to acute stress
Authors: Ma X-M , Levy A , Lightman S L 
Published: December 2004

Abstract
The rapid detection of gene activation is important for our understanding of gene regulation. We have therefore studied heteronuclear (i.e. nascent) RNA (hnRNA) by using 35S-labelled corticotrophin-releasing hormone (CRH) riboprobes and arginine vasopressin (AVP) oligonucleotide probes directed against intronic and exonic sequences of both CRH and AVP transcripts for in situ hybridization studies of transcriptional changes during acute stress. CRH and AVP intronic signals (found in newly synthesized transcripts) were confined to the nuclei of the parvocellular cells in the paraventricular nucleus (PVN) whilst CRH and AVP exonic signals (found in both newly formed and mature transcripts) were primarily located in the cytoplasm of these cells. AVP hnRNA and mRNA were also present at high levels in the magnocellular PVN. The levels of CRH hnRNA and parvocellular AVP hnRNA in the PVN were significantly increased 1 and 2 h after the onset of restraint. The levels of CRH mRNA on the other hand were not significantly increased until 4 h after the onset of restraint. The number of AVP mRNA-expressing neurons in the medial parvocellular cells of the PVN significantly increased at 2 h and peaked at 4 h after the onset of stress. In contrast, densitometric analysis indicated that the increase in AVP mRNA levels in these cells did not reach significant difference from control until 4 h after the onset of restraint. There were no significant changes in AVP hnRNA or AVP mRNA levels in the magnocellular subdivision of PVN at any time point after the onset of restraint.
Journal of Endocrinology (1997) 152, 81–89
Inhibition of L-692,429-stimulated rat growth hormone release by a weak substance P antagonist: L-756,867
Authors: Cheng K , Wei L , Chaung L-Y , Chan W W-S , Butler B , Smith R G 
Published: December 2004

Abstract
H2N,d-Arg,Pro,Lys,Pro,d-Phe,Gln,d-Trp,Phe,d-Trp,Leu, Leu,NH2 (L-756,867), a weak substance P antagonist, inhibited L-692,429-stimulated GH release from rat primary pituitary cells in a dose-dependent manner. At a concentration of 50 nm, L-756,867 shifted the dose–response curve of L-692,429-induced GH release to the right by about tenfold. It also impaired the ability of L-692,429 to potentiate the effect of growth hormone-releasing factor (GRF) on GH release. Substance P (1 μm) had no effect on basal or L-692,429-stimulated GH release. When tested in anesthetized rats, L-756,867 inhibited L-692,429- and growth hormone-releasing hexapeptide- (GHRP-6)-stimulated GH secretion in a dose-dependent manner. Complete inhibition was observed at an i.v. dose of 100 μg/kg of L-756,867. However, at the same concentration, it had no effect on GRF-induced GH secretion. d-Lys3-GHRP-6, a GHRP-6 antagonist, had no effect on GHRP-6 or L-692,429-induced GH secretion even at an i.v. dose of 2 mg/kg. These results indicate that L-692,429 and GHRP-6 stimulate GH release both in vitro and in vivo via a common receptor and signaling pathway which is different from that of substance P in spite of the fact that their effects are inhibited by a weak substance P antagonist.
Journal of Endocrinology (1997) 152, 155–158
Expression patterns of the c-myc gene in adrenocortical tumors and pheochromocytomas
Authors: Liu J , Voutilainen R , Kahri A I , Heikkilä P 
Published: December 2004

Abstract
Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc gene in normal adrenals was localized to the zona fasciculata and zona reticularis, with much lower expression in the zona glomerulosa and adrenal medulla. In hormonally active adrenocortical carcinomas (n=6) and in virilizing adenomas (n=4), c-myc mRNA levels were approximately 10% of those in normal adrenals (n=11). In contrast, adrenal adenomas from patients with Cushing's (n=4) and Conn's (n=9) syndrome, non-functional adenomas (n=2), adrenocortical hyperplasias (bilateral, n=5; nodular, n=4), and non-functional adrenocortical carcinomas (n=3) expressed c-myc mRNA to the same extent as normal adrenals. The c-myc mRNA abundance in benign adrenal pheochromocytomas (n=19) was similar to that in normal adrenal medulla. However, in malignant adrenal pheochromocytomas (n=6), the average c-myc mRNA levels were approximately threefold that in benign adrenal pheochromocytomas. There was a good correlation between c-myc mRNA expression and immunohistochemical reactivity in both normal and pathological adrenal tissues. Southern blot analysis revealed no amplification or rearrangement of the c-myc gene in any of the adrenal tumors.
In conclusion, c-myc expression localized to zona fasciculata and reticularis in normal adrenals. Virilizing adenomas and hormonally active adrenocortical carcinomas expressed c-myc mRNA clearly less than the other adrenal neoplasms and normal adrenal tissue. On the other hand, malignant pheochromocytomas contained more c-myc mRNA than benign ones. Further studies are required to clarify the mechanisms and significance for the distinct expression pattern of the c-myc gene in different adrenal neoplasms.
Journal of Endocrinology (1997) 152, 175–181
Regulatory peptides and other neuroendocrine markers in medullary carcinoma of the thyroid
Authors: Hanna F W F , Ardill J E S , Johnston C F , Cunningham R T , Curry W J , Russell C F J , Buchanan K D 
Published: December 2004

Abstract
Medullary thyroid carcinoma (MTC) is an APUDoma (APUD refers to amine precursor uptake and decarboxylation) arising from the parafollicular cells. Diarrhoea has been reported in some 30% of patients, variously attributed to excess production of calcitonin (CT), serotonin (5-HT), vasoactive intestinal peptide (VIP) or other factors.
The regulatory factors in MTC were examined employing immunocytochemistry and RIA to tumours and their extracts. The patients were followed up for more than 15 years. CT and calcitonin gene-related peptide were universally expressed in all the tumours. The neuroendocrine markers chromogranin A (and its fragments pancreastatin and WE-14), neurone-specific enolase, protein gene product 9·5 and carcino-embryonic antigen were found in the majority of MTCs and might be useful as immunocytochemical markers. 5-HT, substance P, neurokinin A, glucagon and VIP could not be detected, excluding them as candidates in the diarrhoea of MTC.
Journal of Endocrinology (1997) 152, 275–281
Prolactin-like protein-B: heterologous expression and characterization of placental and decidual species
Authors: Cohick C B , Xu L , Soares M J 
Published: December 2004

Abstract
Prolactin-like protein-B (PLP-B) is a member of a family of proteins expressed by the rat placenta and/or decidua with characteristics similar to prolactin (PRL). In this report, we present the heterologous expression and characterization of PLP-B. Recombinant PLP-B heterologously expressed in Chinese hamster ovary cells exhibited similar immunoreactive and electrophoretic characteristics with PLP-B produced by rat placental and decidual tissues. N-terminal sequencing verified the identity and purity of the recombinant PLP-B species and the site of cleavage of the signal peptide from the mature secreted PLP-B species. Polyclonal antibodies were generated to the recombinant PLP-B and used for Western blot and immunocytochemical analyses. Recombinant and native PLP-B migrated as a doublet at 30–31 kDa in SDS-PAGE under reducing conditions. Treatment of recombinant and native PLP-B with N-glycanase accelerated their electrophoretic mobility, indicative of their glycoprotein nature. PLP-B was localized exclusively to decidual cells in the developing deciduum and spongiotrophoblast cells in the placental junctional zone. The level of PLP-B protein expression dramatically declined prior to parturition. Potential PRL-like biological actions of PLP-B were also investigated. PLP-B bound weakly to ovarian and liver PRL receptors and did not stimulate the proliferation of lactogen-dependent Nb2 lymphoma cells. In conclusion, recombinant PLP-B possesses characteristics similar to native decidual and placental PLP-B and may represent a hormone/cytokine that has important modulatory actions during the establishment of pregnancy and the initiation of parturition.
Journal of Endocrinology (1997) 152, 291–302
Additive effects of lactation and food restriction to increase hypothalamic neuropeptide Y mRNA in rats
Authors: Wilding J P H , Ajala M O , Lambert P D , Bloom S R 
Published: December 2004

Neuropeptide Y (NPY) is the most powerful appetite stimulant known, and rates of synthesis and release in the hypothalamus correlate closely with nutritional status. Pregnancy and lactation provide an excellent model of physiological hyperphagia. In this study the authors measured food intake, plasma glucose, insulin and luteinizing hormone (LH) and hypothalamic NPY mRNA in rats during pregnancy and in early and late lactation. The effect of food restriction (to 80% of control) during lactation was also studied. Pregnancy resulted in a modest increase in daily food intake over non-lactating controls (controls: 15·6±0·6 g, pregnant: 19·8±1·1 g, P<0·01) During lactation food intake increased dramatically to 355% of non-lactating levels by the 12th day. Insulin and glucose levels were unchanged in lactation, except in the food-restricted animals, when insulin levels were reduced to 49·5±18·4 pmol/l compared with 215±55 pmol/l (P<0·01) in lactating, non-restricted animals, and glucose was reduced to 3·7±0·2 mmol/l compared with 5·1 ± 0·2 mmol/l in non-restricted lactating animals. Hypothalamic NPY mRNA was unchanged in pregnancy, moderately increased after 5 days lactation (130±6·2% of control, P<0·01) and increased further at 14 days lactation (179 ± 14%, P<0·001). The greatest changes occurred in the animals who were food-deprived during lactation, when hypothalamic NPY mRNA levels reached 324 ± 44% (P<0·001) of non-lactating levels. Increases in hypothalamic NPY synthesis may be partly responsible for the increase in food intake seen in lactation, but unlike in food deprivation, the increase is not related to circulating insulin, suggesting involvement of other regulatory factors.
Journal of Endocrinology (1997) 152, 365–369
Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation
Authors: Nicol M B , Hirst J J , Walker D , Thorburn G D 
Published: December 2004

Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130–133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 ± 121%, n=5, P<0·05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74·4–81·1% and 58–65% respectively, P<0·05, n=5). Four ewes received Trilostane (25 mg i.v.), a 3β-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19·8 ± 8·0% and 39·5 ± 24·3% respectively, P<0·05). The incidence of fetal EOG activity increased from a pretreatment level of 26·8 ± 1·5 min/h to 30·3 ± 2·8 min/h at 1–6 h and to 35·0 ± 1·7 min/h (P<0·05) during the 7–12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1–6 h and 7–12 h after Trilostane treatment (19·5 ± 3·0 and 23·6 ± 5·5 min/h respectively, P<0·05) compared with pretreatment levels (11·2 ± 1·2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM.
Journal of Endocrinology (1997) 152, 379–386
Effects of growth hormone on cholesterol metabolism in the lactating rat mammary gland
Authors: Shand J H , West D W , Flint D J 
Published: December 2004

Lactating rats were treated for 48 h with bromocriptine (to inhibit prolactin release) or bromocriptine together with an antiserum to rat GH. Animals given the combined treatment were also supplemented concurrently with bovine GH (bGH) or human insulin-like growth factor-I (hIGF-I). The effects of these treatments on the activities of 3-methyl-3-glutaryl-CoA reductase (HMG-CoA reductase), acyl-CoA:cholesterol acyltransferase (ACAT) and neutral cholesteryl ester hydrolase (CEH) and on the microsomal concentrations of non-esterified and esterified cholesterol were measured.
Lack of prolactin decreased HMG-CoA reductase but did not affect ACAT, neutral CEH or the concentrations of microsomal cholesterol or cholesteryl esters. In the absence of both hormones, an even greater reduction in HMG-CoA reductase together with increases in ACAT, neutral CEH and both of the microsomal sterols were observed. Concurrent supplementation with either bGH or hIGF-I wholly or partially prevented the effects on HMG-CoA reductase but only bGH was active against the increase in ACAT. Neither bGH nor hIGF-I could prevent the effects of the anti-hormone treatment on neutral CEH, and the changes in ACAT and CEH activities were broadly reflected in the microsomal sterol concentrations.
The results indicate that the cessation of lactation brings about rapid changes in the activities of the enzymes involved in cholesterol metabolism within the mammary gland with a definite switch from synthesis to storage. Supplementation with bGH alone was sufficient to maintain cholesterol synthesis at control levels and could also significantly inhibit storage of the sterol as its ester. In the absence of GH, hIGF-I partially supported cholesterol synthesis but had no effect on its conversion to the ester. On a whole-tissue basis, enzyme activities could be correlated with the physiological effects of the anti-hormone treatments.
Journal of Endocrinology (1997) 152, 447–454
Regulation of lipolysis by somatotropin: functional alteration of adrenergic and adenosine signaling in bovine adipose tissue
Authors: Houseknecht K L , Bauman D E 
Published: December 2004

To investigate the cellular mechanisms of somatotropin (ST) action on adipose tissue lipolysis, experiments were conducted using adipose tissue taken from lactating cows treated with excipient or ST (40 mg/day). Stimulation of lipolysis in vitro by the effectors isoproterenol with or without adenosine deaminase, dibutyryl cAMP with or without isobutylmethylxanthine, and forskolin was not altered by ST treatment. Conversely, the response to the antilipolytic effector, phenylisopropyladenosine (PIA), was significantly reduced in adipose tissue explants from ST or fasted cows. The different responses to adrenergic-stimulating agents (in vivo) and PIA (in vitro) were not due to differences in the abundance of α, β or γ subunits of the stimulatory (Gs) and inhibitory (Gi) subunits of the heterotrimeric G-proteins which bind to the β-adrenergic and adenosine receptors respectively. However, the functionality of Gi proteins, as assessed by their ability to be ADP-ribosylated by pertussis toxin, was significantly reduced in ST-treated but not fasted cows. These data highlight differential regulation of signaling proteins by ST and fasting, both of which result in enhanced in vivo response to adrenergic stimulation of lipolysis.
Journal of Endocrinology (1997) 152, 465–475
Hypothalamo–pituitary–adrenal axis response to coronary artery embolization: an ovine model of acute myocardial infarction
Authors: Charles C J , Rogers S J , Donald R A , Ikram H , Prickett T , Richards A M 
Published: December 2004

Although previous studies have described the hypothalamo–pituitary–adrenal (HPA) response to the stress of acute myocardial infarction, it is not possible to study the hormone changes immediately after infarction in humans. Accordingly, we have examined the HPA response to microembolization of coronary arteries in 13 sheep compared with 5 sham control sheep. Plasma vasopressin (AVP; P<0·001), ACTH (P=0·005) and cortisol (P=0·005) were all increased 2 h (first sample time) after embolization. Plasma ACTH and cortisol levels returned to baseline levels by 6 h but plasma AVP levels did not return to baseline levels until more than 12 h after embolization. Plasma corticotrophin-releasing hormone (CRH) showed no significant change in response to embolization. In a subset of six animals which were sampled more frequently, the peak responses for plasma AVP, ACTH and cortisol occurred at 40 min after embolization. The maximum responses in any individual sheep observed at this time point were 744 pmol/l for AVP, 144 pmol/l for ACTH and 492 nmol/l for cortisol. CRH levels tended to increase across the first hour but these changes were not statistically significant. In conclusion, the stress hormone responses to microembolization of the coronary arteries have been defined in an ovine model of myocardial infarction. This model is suitable for studying the effects of novel treatments to reduce the stress of myocardial infarction.
Journal of Endocrinology (1997) 152, 489–493
Prostaglandin F2α promotes the inhibitory action of endothelin-1 on the bovine luteal function in vitro
Authors: Miyamoto A. , Kobayashi S. , Arata S. , Ohtani M. , Fukui Y. , Schams D. 
Published: December 2004

ABSTRACT
Prostaglandin F2α (PGF2α) is a primary luteolysin in the cow. Although the mechanisms involved in luteolysis are thought to be a complex of its direct action on luteal cells and indirect effect on luteal blood flow, the detailed mechanisms remain to be elucidated. This study focuses on the possible interaction of endothelial cells-derived endothelin-1 (ET-1) with PGF2α in the rapid suppression of progesterone release from the bovine corpus luteum (CL). In in vitro microdialysis system (MDS) of CL, PGF2α acutely stimulated the release of progesterone and oxytocin during infusion and ET-1 release after infusion. Moreover, PGF2α induced slight decrease of progesterone release during the last period of the experiment (8-11 h after PGF2α exposure). Two 1 h-perfusions of ET-1 at 3 h intervals induced only a slight decrease of progesterone release after the second perfusion. This treatment also affected the oxytocin release; the first ET-1 perfusion produced an acute stimulation, whereas the second ET-1 perfusion inhibited the release to below 50%. When the CL pieces were pre-perfused with PGF2α for 2 h, the two consecutive perfusion of ET-1 at 3 h intervals induced drastic decrease in progesterone and oxytocin release only after the second ET-1 perfusion. Thus, a pre-exposure with PGF2α clearly potentiated the inhibiting activity of ET-1 in the progesterone release. These results suggest a physiological impact of PGF2α and ET-1 in the rapid cascade of functional luteolysis in vivo, and a possible interaction between endothelial cells and luteal cells.