bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent inhibitory effects of steroids in an in vitro model of angiogenesis
Authors: Jaggers D C , Collins W P , Milligan S R 
Published: December 2004

Abstract
The regulation of angiogenesis in the ovarian follicle and corpus luteum is unclear. Steroids are produced at very high concentrations in these tissues and we therefore examined the effect of steroids on angiogenesis in vitro. Explants of rat aorta were embedded in collagen gel and cultured in serum-free medium. Capillary-like microvessels were produced from the explants and microvessel number and length were measured in the presence and absence of steroids. At a concentration of 10 μg/ml, cortisol, progesterone, 17α-hydroxyprogesterone and medroxyprogesterone acetate produced degeneration of microvessels after 7 days of steroid treatment (P<0·01). Androstenedione and tetrahydro-S-(11-deoxytetrahydro-cortisol) (tetrahydro S) produced degeneration at a slower rate: androstenedione inhibited microvessel growth after 11 days (P<0·01) and tetrahydro S after 14 days (P<0·05). Oestriol had no effect on microvessels; oestrone had a slow degenerative effect with significant inhibition seen after 14 days (P<0·01). Oestradiol-17β at a concentration of 10 μg/ml completely inhibited microvessel growth from the explant cultures (P<0·01) while at 1 μg/ml it caused degenerative effects on growing microvessels. The effects of oestradiol and cortisol were reversible on removal of steroid-containing medium and replacement with 10% serum. We conclude that oestradiol may modulate angiogenesis in tissues in which the steroid concentration is high.
Journal of Endocrinology (1996) 150, 457–464
Localization of prostaglandin H synthase type 2 protein and mRNA in term human fetal membranes and decidua
Authors: Gibb W , Sun M 
Published: December 2004

Abstract
Prostaglandin (PG) production by human fetal membranes (amnion and chorion laeve) may be important in the onset and progression of labour, cervical ripening and membrane rupture. Prostaglandin H synthase (PGHS) is a key enzyme in PG formation and has two isoforms, a constitutive form (PGHS-1) and an inducible form (PGHS-2). The present study examined the cellular distribution of the PGHS-2 enzyme and PGHS-2 mRNA in term human fetal membranes and decidua prior to and following labour, using immunohistochemistry and in situ hybridization with an 35S-labelled oligonucleotide probe. The PGHS-2 protein was found to be localized in amnion epithelial cells and chorion laeve trophoblast, but was absent or at low levels in the decidual stroma in most tissues, although cells surrounding some of the blood vessels in the decidua did express PGHS-2. In situ hybridization demonstrated that PGHS-2 mRNA had a similar distribution and was localized to amnion epithelial cells, cells in the amnion-chorion mesenchyme, chorion laeve trophoblast and, occasionally, to cells surrounding blood vessels in the decidua. Of particular note was the high mRNA expression in some cells and low expression in other cells, particularly in the chorion, and the low level of PGHS-2 mRNA in decidua. There was no observable difference in the cellular localization of PGHS-2 protein or PGHS-2 mRNA in tissues obtained prior to and following labour. The studies indicate that, at term, the inducible form of PGHS, PGHS-2, is expressed at a high level in fetal tissues in a number of different cell types rather than in the maternal decidua.
Journal of Endocrinology (1996) 150, 497–503
Follistatin concentrations in male sheep increase following sham castration/castration or injection of interleukin-1β
Authors: Phillips D J , Hedger M P , McFarlane J R , Klein R , Clarke I J , Tilbrook A J , Nash A D , de Kretser D M 
Published: December 2004

Abstract
Plasma follistatin (FS) concentrations were determined after castration (n=5) or sham castration (n=4) of mature rams. Both treatments resulted in a prolonged increase in FS between 7 and 19 h after surgery, which returned to pretreatment concentrations by 24 h. Tumour necrosis factor-α (TNF-α), a sensitive marker of an acute-phase response, was undetectable in plasma, indicating that the FS response was not induced by trauma due to surgery. In a second experiment, injection of castrated rams (n=4) with ovine recombinant interleukin-1β, an acute-phase mediator, resulted in a sustained rise in FS concentrations within 4 h of injection. Plasma TNF-α concentrations increased transiently within 1 h of interleukin-1β injection, indicating that an acute-phase response had been initiated. Plasma follicle-stimulating hormone (FSH) concentrations were significantly decreased at 8 and 24 h after interleukin-1β injection, strongly suggestive of an inhibitory effect of increased FS concentrations on the secretion of FSH. Injection of castrated rams (n=2) with a control preparation of recombinant interleukin-2 did not induce an acute-phase response, and plasma FS and FSH concentrations were unaffected. These data show that the testis is not a major source of circulating FS, that the increase in circulating FS following sham castration/castration is not due to an acute-phase response, but that conversely FS concentrations are modulated by the acute-phase mediator, interleukin-1β.
Journal of Endocrinology (1996) 151, 119–124
Expression of mRNAs for insulin-like growth factor binding proteins-2, -3 and -4 in the ovine ovary throughout the oestrous cycle
Authors: Perks C M , Wathes D C 
Published: December 2004

Abstract
Ovarian localization of the IGFs and their binding proteins is species-specific. In the ewe we have demonstrated previously that IGF-II mRNA is found at high concentrations in the theca, whereas IGF-I mRNA is undetectable in ovine follicles at any stage of development, although both are present in the corpus luteum. In this study we have investigated the localization of mRNA for IGF-binding proteins (IGFBPs)-2, -3 and -4 using in situ hybridization to further elucidate the roles of the IGFs and their possible modulation during follicular development. Results were quantified by optical density (OD) measurements of autoradiographs using image analysis. There was intense follicular expression of mRNAs for both IGFBP-2 and -4 although IGFBP-3 mRNA was undetectable. Concentrations of IGFBP-2 mRNA varied significantly (P<0·01) with respect to size, being highest in small (<2 mm) follicles but with no variation attributable to health, whereas expression of IGFBP-4 mRNA was significantly (P<0·01) influenced by health and not size, being higher in healthy than atretic follicles. IGFBP-2, -3 and -4 mRNAs were all present at low concentrations in the corpus luteum (OD 0·04 ± 0·005, n=6; 0·05 ± 0·02, n=5; 0·1 ± 0·02, n=8 respectively), whereas only IGFBP-2 and -4 mRNAs were found in ovarian stroma (OD 0·04 ± 0·006, n=4; 0·04 ± 0·007, n=9 respectively). These data suggest that changes in follicular distribution of IGFBPs-2 and -4 may modulate the actions of the IGFs during follicular growth thus contributing to the process of follicle selection.
Journal of Endocrinology (1996) 151, 241–249
The steroidogenic effects of β-endorphin and joining peptide: a potential role in the modulation of adrenal androgen production
Authors: Clarke D , Fearon U , Cunningham S K , McKenna T J 
Published: December 2004

Abstract
This study examines the androgen-stimulating properties of pro-opiomelanocortin-derived peptides, ACTH, β-endorphin (β-End) and joining peptide (JP). Ten different cell suspensions were prepared from ten human adrenal glands. ACTH and JP stimulated cortisol, androstenedione (Δ4) and dehydroepiandrosterone (DHEA) production (P<0·05); β-End stimulated only Δ4 and DHEA production. β-End brought about significant increases in the Δ4 or DHEA to cortisol ratios. The addition of β-End (10−10 m) suppressed ACTH-stimulated cortisol production from 7573 ± 2960 to 5994 ± 2654 pmol/106 cells (means ± s.e.m.; P<0·05). The addition of β-End did not affect ACTH-stimulated Δ4 production (210 ± 88 and 236 ± 105 pmol/106 cells). JP (10−10 m) inhibited ACTH-stimulated cortisol production so that the mean values fell to 5186 ± 2588 and also inhibited DHEA production, from 240 ± 48 to 180 ± 33 pmol/106 cells. These results suggest that the relative production of androgen to cortisol is greater in response to β-End and JP than in response to ACTH. If blood levels of these peptides rise to herald adrenarche as reported for β-End, suppression of cortisol production may result in an increase in ACTH to correct cortisol levels resulting in an increase in Δ4 and DHEA levels. This may explain the occurrence of increasing androgen levels at adrenarche.
Journal of Endocrinology (1996) 151, 301–307
A comparison of cytokine and hormone production by decidual cells and tissue explants
Authors: Lonsdale L B , Elder M G , Sullivan M H F 
Published: December 2004

Abstract
Previous work has shown that enzymatic digestion of human placental tissue can induce the production of the cytokine interleukin-1β. Most studies of the feto-maternal interface of human pregnancy have used decidual cells prepared in a similar way, but the effects of tissue dissociation on the production of growth factors, cytokines, prostaglandins or hormones have not been investigated. Our studies show human decidual explants produce substantially lower levels of a range of factors than do human decidual cells cultured under the same conditions, indicating that induction may be a general process during the dissociation of tissues in vitro as the production of interleukins-1β, -6 and -8, granulocyte-macrophage colony-stimulating factor, transforming growth factor-β2, tissue necrosis factor-α, prostaglandins E2 and F2α, and prolactin were all affected. The induction of cytokine production (expressed per mg tissue protein) ranged from 10- to 300-fold, indicating that isolated cells cultured in vitro may not reflect accurately the in vivo situation.
Journal of Endocrinology (1996) 151, 309–313
Benign prostatic stromal cells are regulated by basic fibroblast growth factor and transforming growth factor-β1
Authors: Collins A T , Robinson E J , Neal D E 
Published: December 2004

Abstract
The current study was undertaken, using cultures of prostatic epithelial and stromal cells, to determine the functional interactions between androgens, basic fibroblast growth factor (FGF2) and transforming growth factor-β1 (TGFβ1) and their importance in maintaining stromal homeostasis. Treatment of stromal cells with TGFβ1 significantly increased intracellular FGF2 and FGF2 sequestered to the extracellular matrix. FGF2 was also detected in stromal conditioned medium (SCM), but at levels 70-fold less than found in cell lysates. TGFβ1 (0·1 ng/ml) treatment caused an initial increase of 86% in secreted FGF2 levels, but high concentrations of TGFβ1 (5 ng/ml) decreased FGF2 levels by 38%, relative to the untreated control. Further studies showed that epithelial conditioned medium (ECM), androgen-treated, stromal conditioned medium (ASCM), but not SCM were mitogenic for stromal cells. Both ECM and ASCM caused a threefold increase in DNA synthesis. FGF2 may be the mediator of these interactions, since the mitogenic effect of both ECM and ASCM was significantly reduced by the addition of anti-FGF2 neutralising antibody. We hypothesise that the lack of response of stromal cells to SCM is due to TGFβ1 blocking the mitogenic effect of FGF2. Thus down-regulation of TGFβ1 synthesis, by androgens, results in stromal proliferation by ASCM.
Journal of Endocrinology (1996) 151, 315–322
Mechanisms of amino acid-induced insulin secretion from the glucose-responsive BRIN-BD11 pancreatic B-cell line
Authors: McClenaghan N H , Barnett C R , O'Harte F P M , Flatt P R 
Published: December 2004

Abstract
The effects of different classes of amino acids known to be transported and utilized by pancreatic B-cells were examined using the novel glucose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included α-aminoisobutyric acid, l-alanine, l-arginine, l-glutamine, glycine, l-leucine, l-lysine, l-proline and l-serine. At non-stimulatory (1·1 mmol/l) glucose, acute incubations with either 1 or 10 mmol/l amino acid evoked 1·3- to 4·7-fold increases of insulin release. Raising glucose to 16·7 mmol/l enhanced the effects of all amino acids except l-glutamine, and increased insulin output at 10 mmol/l compared with 1 mmol/l amino acid. Glyceraldehyde (10 mmol/l) also served to promote 10 mmol/l amino acid-induced insulin secretion with the exceptions of l-arginine, glycine, l-lysine and l-proline. At 16·7 mmol/l glucose, diazoxide (300 μmol/l) significantly decreased the secretory response to all amino acids except l-glutamine. Likewise, verapamil (20 μmol/l) or depletion of extracellular Ca2+ reduced insulin output indicating the importance of Ca2+ influx in the actions of amino acids. These data indicate that BRIN-BD11 cells transport and utilize amino acids, acting in association with glycolysis, K+-ATP channels and/or voltage-dependent Ca2+ channels to promote Ca2+ influx and insulin secretion. The response of BRIN-BD11 cells to glucose and amino acids indicates that this is a useful cell line for future research on the mechanisms of nutrient regulation of insulin secretion.
Journal of Endocrinology (1996) 151, 349–357
Luminal peptide YY-releasing factors in the isolated vascularly perfused rat colon
Authors: Plaisancié P , Dumoulin V , Chayvialle J-A , Cuber J-C 
Published: December 2004

Abstract
Peptide YY (PYY) is produced in endocrine L cells primarily localized in the distal bowel. These open-type L cells make contact with the intestinal chyme which may thus affect their secretory activity. The aim of the present study was to examine a large variety of luminal compounds found in colonic contents for their potential as PYY-releasing factors, using the isolated vascularly perfused rat colon. The release of PYY into the portal effluent was measured by a specific RIA. Luminal administration of 5 mm glucose or 0·5% (w/v) starch for 30 min did not induce significant release of PYY. Oleic acid (10 and 100 mm) also did not significantly increase PYY secretion. A pharmacological concentration of glucose (250 mm) and a mixture of amino acids (total concentration 250 mm) both induced PYY secretion (200% of basal). Pectin, a polygalacturonic acid, evoked dose-dependent secretion of PYY-like immunoreactivity over the range 0·1–0·5% (w/v). The maximal response was observed after infusion of 0·5% pectin which induced a prompt and sustained release of PYY (300% of basal). Galacturonic acid itself (5%) produced marked PYY secretion. Gum arabic (0·5%) induced a gradual increase in portal PYY concentration (maximal response 250% of the basal value) whereas cellulose (0·5%) did not elicit PYY secretion. Luminal n-butyrate over the range 0·5–5 mm produced a dose-dependent release of PYY (maximal response 300% of the basal value with 5 mm n-butyrate). Increasing the concentration of n-butyrate to 100 mm provoked a gradual decrease in PYY secretion. Propionate was a less potent stimulant than n-butyrate, and acetate did not increase PYY secretion above the basal value. At a concentration of 2 or 20 mm, taurocholate, cholate and deoxycholate brought about PYY secretion while hyodeoxycholate was without effect.
In conclusion, glucose and amino acids may mediate PYY release but only when they are present at high supraphysiological concentrations in the colon while oleic acid does not produce any PYY secretion. Physiological concentrations of fibers (pectin, gum arabic), short-chain fatty acids (n-butyrate, propionate) and bile salts (taurocholate, cholate, deoxycholate) are all potent stimulants of PYY release. Whether the release of PYY by luminal factors is coupled to water and electrolyte transfer via a local/paracrine pathway remains an open question which requires additional work with the isolated vascularly perfused colon preparation.
Journal of Endocrinology (1996) 151, 421–429
Dopaminergic regulation of adrenocorticotrophic hormone, α-melanocyte-stimulating hormone and cortisol secretion in the ovine fetus
Authors: Hagan D M , Brooks A N 
Published: December 2004

Abstract
During ovine fetal development there is a progressive maturation of the hypothalamo–pituitary–adrenal axis which culminates in the onset of birth. The role and regulation of the intermediate lobe of the fetal pituitary gland in relation to this maturational process remains controversial. To test the hypothesis that the pars intermedia of the ovine fetal pituitary is under tonic inhibitory dopaminergic control we treated fetal sheep at day 131 of gestation with a 3-day intravenous infusion of one of the following: the dopamine antagonist sulpiride (0·3 mg/0·5 ml/h; n=12), the dopamine agonist bromocriptine (0·03 mg/0·5 ml/h; n=7) or vehicle (0·1 m tartaric acid in saline; n=8) alone. Fetal plasma concentrations of α-MSH were significantly (P<0·01) increased by treatment with sulpiride and decreased (P<0·05) by bromocriptine. The increase in α-MSH after sulpiride was characterised by an increase in the amplitude of α-MSH pulses whereas bromocriptine virtually abolished all pulses of α-MSH. Immunoreactive ACTH (IR-ACTH) concentrations were significantly (P<0·05) elevated after sulpiride but were unaffected by bromocriptine. There were no changes in the pulsatile characteristics of IR-ACTH secretion. Cortisol concentrations were unchanged by either treatment. We conclude that fetal α-MSH and IR-ACTH are secreted in a pulsatile fashion and are tonically inhibited by dopaminergic pathways. The lack of an effect of endogenously raised α-MSH on plasma cortisol concentrations provides evidence that this POMC-derived peptide is not responsible for the regulation of cortisol biosynthesis and/or secretion.
Journal of Endocrinology (1996) 151, 439–447
Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its level is enhanced by type-β transforming growth factor
Authors: Liu Y , Cserjesi P , Nifuji A , Olson E N , Noda M 
Published: December 2004

Abstract
Scleraxis is a recently identified transcription factor with a basic helix-loop-helix motif, which is expressed in sclerotome during embryonic development. We have examined the expression of scleraxis mRNA in rat osteoblastic cells and found that the scleraxis gene was expressed as a 1·2 kb mRNA species in osteoblastic osteosarcoma ROS 17/2·8 cells. The scleraxis mRNA expression was enhanced by type-β transforming growth factor (TGFβ) treatment. The TGFβ effect was observed in a dosedependent manner starting at 0·2 ng/ml and saturating at 2 ng/ml. The effect was time-dependent and was first observed within 12 h and peaked at 24 h. The TGFβ effect was blocked by cycloheximide, while no effect on scleraxis mRNA stability was observed. TGFβ treatment enhanced scleraxis-E box (Scx-E) binding activity in the nuclear extracts of ROS17/2·8 cells. Furthermore, TGFβ enhanced transcriptional activity of the CAT constructs which contain the Scx-E box sequence. TGFβ treatment also enhanced scleraxis gene expression in osteoblastenriched cells derived from primary rat calvaria. These findings indicated for the first time that the novel helixloop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its expression is regulated by TGFβ.
Journal of Endocrinology (1996) 151, 491–499
Diet-induced obesity and pancreatic islet blood flow in the rat: a preferential increase in islet blood perfusion persists after withdrawal of the diet and normalization of body weight
Authors: Svensson A M , Hellerström C , Jansson L 
Published: December 2004

Abstract
The aim of the present study was to evaluate the effects of diet-induced obesity on pancreatic islet blood perfusion in normal Wistar rats. Furthermore, we investigated to what extent any obesity-associated changes in islet blood flow could be reversed after reversion to a normal diet with normalization of body weight. Young adult female Wistar rats were offered a palatable mixed high-caloric diet (cafeteria diet) in addition to standard pelleted chow. Age-matched control rats received standard pelleted chow only. After 4 weeks the diet-treated rats had a body weight of approximately 15% more than that of the controls. All diet-treated rats had decreased glucose tolerance and increased serum insulin concentrations, but basal blood glucose concentrations were similar in anesthetized diet-treated and control rats. Whole pancreatic and islet blood flow rates were measured with a microsphere technique. The islet blood flow as well as fractional islet blood flow were increased (P<0·01) in rats fed the cafeteria diet, while blood perfusion of the whole pancreas was similar to that of the control rats. In a second experiment, rats received the cafeteria diet for 4 weeks and were then fed standard pelleted food alone for another 3 weeks, while controls received standard diet for 7 weeks. After this period total body weight, retroperitoneal fat pad weight and glucose tolerance were similar to those of the controls. Whole pancreatic blood flow was unchanged as compared with that of control rats. However, both islet blood flow (P<0·01) and fractional blood flow (P<0·01) were increased. We conclude that diet-induced obesity in rats is associated with decreased glucose tolerance, hyperinsulinemia and a specific increase in absolute and fractional islet blood perfusion. This increase persists for at least 3 weeks after the diet is withdrawn despite normalization of body weight and glucose tolerance.
Journal of Endocrinology (1996) 151, 507–511
Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro
Authors: Hatton R , Stimpel M , Chambers T J 
Published: December 2004

Abstract
During bone resorption, osteoclasts are closely associated with endothelial cells. The latter are able to produce several agents that regulate bone resorption. In view of the increasing evidence that angiotensin II, which can be generated by endothelial cells, has actions outside the traditional renin-angiotensin system, we tested the effect of angiotensin II on bone resorption. Angiotensin II showed no effect either on osteoclast formation or on bone resorption by isolated osteoclasts. However, in co-cultures of osteoclasts with calvarial or MC3T3-E1 osteoblastic cells, and in osteoclastic cultures co-cultured with other bone cells obtained by prolonged sedimentation, angiotensin II stimulated bone resorption to a similar degree to that observed with 1,25(OH)2 vitamin D3. Stimulation of resorption was noted at concentrations of 10−7 m and above. We found that angiotensin I also stimulated bone resorption in co-cultures of osteoclasts with osteoblastic cells, and that this action was inhibited by inhibitors of angiotensin-converting enzyme. These results identify angiotensin I and II as potent stimulators of osteoclastic bone resorption, and raise the possibility that bone might contain a tissue-renin-angiotensin system that might play a role in the regulation of bone resorption.
Journal of Endocrinology (1997) 152, 5–10