bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediation by the central nervous system is critical to the in vivo activity of the GH secretagogue L-692,585
Authors: Hickey G J , Drisko J , Faidley T , Chang C , Anderson L L , Nicolich S , McGuire L , Rickes E , Krupa D , Feeney W , Friscino B , Cunningham P , Frazier E , Chen H , Laroque P , Smith R G 
Published: December 2004

Abstract
To investigate the effect of hypophyseal transection (HST) on GH secretagogue activity of the non-peptidyl GH secretagogue L-692,585 in the conscious pig, male castrated swine were randomly assigned to either a hypophyseal stalk transection group (HST; n=3) or to a sham-operated control group (SOC; n=3). Treatments administered were L-692,585 (100 γg/kg), human GH-releasing factor(1–29)NH2 (GRF; 20 γg/kg) or L-692,585 (100 γg/kg) + GRF (20 γg/kg) on days −7 to −3 before surgery and days +3 to +8 after surgery. To evaluate the integrity of the pituitary gland, the animals were challenged with corticotropin-releasing hormone (CRH; 150 γg) or GnRH (150 ng/kg) both before and after surgery. Blood was collected from −60 to +180 min post treatment and assayed for GH, cortisol and LH.
Before surgery, no significant difference (P>0·05) in peak GH response (ng/ml) was present between the two groups (SOC vs HST) in response to L-692,585 (101 ± 12 vs 71 ± 9) or L-692,585 + GRF (171 ± 21 vs 174 ± 21). Only two out of three SOC vs three out of three HST pigs responded to GRF (13 ± 2 vs 25 ± 3) resulting in a significant difference between groups. Following surgery, significant differences were present in peak GH response (ng/ml) between SOC and HST groups following L-692,585 (79 ± 6 vs 13·8 ± 1·0); however, the response to L-692,585 + GRF was similar (115 ± 8 vs 94 ± 7). All animals responded to GRF; however, a significant difference was present between groups due to the magnitude of the responses. Whereas the cortisol responses (ng/ml) to L-692,585 in the SOC and HST groups were similar before surgery, a significant difference was present after surgery (44·4 ± 6·4 vs 14·6 ± 2·1). No significant difference was noted between the HST and SOC groups in response to CRH or GnRH either before or after surgery.
These results indicated that L-692,585 induced an immediate GH response in the intact animal in contrast to GRF where the GH release was variable. L-692,585 also stimulated an immediate increase in cortisol levels. Transection of the hypophyseal stalk dramatically decreased but did not ablate the GH or cortisol response to L-692,585. Co-administration of L-692,585 + GRF induced an immediate GH response of similar magnitude in the intact and HST animal. We conclude that L-692,585 has a direct but limited action at the level of the pituitary and that an intact hypophyseal stalk is required for a maximal GH and cortisol response. L-692,585 acts with GRF at the level of the pituitary to induce a maximal GH response. These findings suggest that L-692,585 stimulates GH secretion by acting in combination with GRF and interrupting the inhibitory tone of somatostatin on the somatotroph.
Journal of Endocrinology (1996) 148, 371–380
Characteristics of BRIN-BG5 and BRIN-BG7, two novel glucose-responsive insulin-secreting cell lines produced by electrofusion
Authors: McClenaghan N H , Barnett C R , O'Harte F P M , Swanston-Flatt S K , Ah-Sing E , Flatt P R 
Published: December 2004

Abstract
Two hybrid insulin-secreting cell lines (BRIN-BG5 and BRIN-BG7) were established by the novel approach of electrofusing RINm5F cells with New England Deaconess Hospital rat pancreatic islet cells. Cells were selected from the fusion mixture on the basis of insulin output. Wells showing five to ten times greater insulin output than parental RINm5F cells were selected, subcultured and cloned. Clonal BRIN-BG5 and BRIN-G7 cells grow as monolayers with epithelial morphology. The differences in doubling time of 28 and 20 h respectively were associated with morphological differences; the growth pattern and insulin content of each cell line remaining stable for over 50 passages. In acute 20-min tests, both cell lines showed peak secretory responses (1·9- and 1·8-fold respectively) to 8·4 mmol/l glucose. Membrane depolarization with 25 mmol/l K+ evoked 3·7- and 3·9-fold increases in insulin output. l-Alanine (10 mmol/l) also served to promote 2·4- and 1·6-fold increases in insulin release respectively. Increasing the Ca2+ concentration from 1·28 to 7·68 mmol/l potentiated this effect by 1·8- and 1·5-fold. Incubation with forskolin (25 μmol/l) or phorbol-12-myristate 13-acetate (10 nmol/l), in the presence of l-alanine, similarly enhanced the secretory effect on BRIN-BG5 and BRIN-BG7 cells by 1·3- to 2·1-fold and 1·2- to 1·5-fold respectively. The presence of a functional glucose-sensing mechanism in both cell lines was confirmed by the demonstration of the glucose transporter GLUT-2 and measurement of glucokinase activity. These functional properties suggest that insulin-secreting BRIN-BG5 and BRIN-BG7 cells represent two useful glucoseresponsive cell lines for future studies of the function of the pancreatic B-cell.
Journal of Endocrinology (1996) 148, 409–417
Follicular variation in ovarian 11β-hydroxysteroid dehydrogenase (11βHSD) activities: evidence for the paracrine inhibition of 11βHSD in human granulosa-lutein cells
Authors: Michael A E , Gregory L , Thaventhiran L , Antoniw J W , Cooke B A 
Published: December 2004

Abstract
We have previously shown that detectable metabolism of cortisol to cortisone by 11β-hydroxysteroid dehydrogenase (11βHSD) in human granulosa-lutein cells, pooled for each patient from all aspirated ovarian follicles, is associated with failure to conceive by in vitro fertilization and embryo transfer. The aims of the present study were to assess: (1) the variation in the 11β-HSD activities of granulosa-lutein cells obtained from individual follicles in relation to oocyte maturity and (2) whether the 11βHSD activity of pooled granulosa-lutein cells reflects the 11βHSD activities of the individual follicles for a given patient. 11βHSD activities were measured in intact cells in serum-free medium by a radiometric conversion assay (100 nmol/l [ 3H]cortisol to [3H]cortisone). Follicular 11βHSD activities ranged from <10 (undetectable) to 514 pmol/mg protein per 4 h (n=105 follicles from 12 patients) and did not correlate with oocyte maturity. In three separate patients, the follicular 11βHSD activities ranged from <10 to 117 pmol/mg protein per 4 h (n=8 follicles), 19 to 514 pmol/mg per 4 h (n=9) and 60 to 390 pmol/mg per 4 h (n=8). The 11βHSD activities of the corresponding multi-follicular pools of cells were <10, <10 and 44 pmol/mg per 4 h respectively, all of which were significantly lower (P<0·05) than the arithmetic means for the activities in the individual follicles (52, 132 and 215 pmol/mg per 4 h respectively). Likewise, the 11βHSD activities of two independent multi-patient pools of cells were significantly lower than the mean values of the 11βHSD activities of the appropriate individual patients. We conclude that ovarian 11βHSD activity varies between follicles and that co-culture of granulosa-lutein cells with low enzyme activity can suppress the ovarian 11βHSD activity in cells from different follicles (or patients) with high rates of cortisol metabolism. Hence, these data indicate the potential for paracrine inhibition of ovarian 11βHSD activity in human granulosa-lutein cells.
Journal of Endocrinology (1996) 148, 419–425
11β-Hydroxysteroid dehydrogenase in developing rat intestine
Authors: Pácha J , Mikšík I 
Published: December 2004

Abstract
The enzyme 11β-hydroxysteroid dehydrogenase (11β-OHSD) prevents the binding of corticosterone to mineralocorticoid receptors by reversible conversion of biologically active corticosterone to inactive 11-dehydrocorticosterone. To clarify the relationship between high plasma concentrations of corticosterone during weaning and high activity of intestinal transport pathways that are induced by aldosterone in immature intestine, we have studied the distribution, developmental pattern and regulation of 11 β-OHSD in intestinal segments that possess mineralocorticoid target epithelium. Dehydrogenase activity was already high in the caecum, and the proximal and distal colon on the second postnatal day and altered little until adulthood. In contrast, the activity in the ileum was low during the first two weeks of life, rose more than 5-fold in the next 20 days to attain a peak in 30-day-old rats, and thereafter declined to the values of adult animals. There was no significant reductase activity (conversion of 11-dehydrocorticosterone to corticosterone) in any intestinal segment of young and adult rats. The regulation of intestinal 11β-OHSD by corticosteroids and thyroid hormones was studied in the ileum and distal colon. In weanling rats, adrenalectomy or a high-salt diet decreased 11β-OHSD activities in both intestinal segments whereas dexamethasone administration prevented this decline in adrenalectomized rats and administration of deoxycorticosterone acetate led to a significant increase of intestinal 11β-OHSD activities in rats kept on a high-salt diet. Dexamethasone administration to intact adult rats also stimulated 11 β-OHSD activity in the ileum and distal colon. The changes in thyroid status of weanling rats did not change the 11β-OHSD activities. We conclude that (1) the developmental patterns of 11β-OHSD activity in the small and large intestine are not identical and this discrepancy may facilitate the maturation effect of glucocorticoids in the small intestine and the stimulatory effect of aldosterone in the large intestine and (2) corticosteroids but not thyroid hormones can modulate 11β-OHSD activity in the developing intestine.
Journal of Endocrinology (1996) 148, 561–566
Characterization of transforming growth factor-α receptors in the avian ovary: alterations in ligand binding to granulosa cells during follicular maturation
Authors: Onagbesan O M , Woolveridge I , Peddie M J 
Published: December 2004

Abstract
The presence of epidermal growth factor receptors (EGF-R) and the ligands epidermal growth factor/transforming growth factor-α (EGF/TGFα) have been reported in mammalian ovaries where they are implicated in folliculogenesis and steroidogenesis. Evidence is presented to show that authentic EGF/TGFα receptors are expressed by the avian granulosa cells. The TGFα receptors (TGFα-R) from chicken granulosa cells were characterized by specific binding of 125I-human TGFα. In this study, competition with human EGF, human TGFα, human IGF-I, human basic fibroblast growth factor (bFGF) and insulin for 125I-human TGFα binding demonstrated that the avian granulosa cell TGFα-R binds human EGF with 300-fold lower affinity than human TGFα. IGF-I, bFGF and insulin did not displace bound 125I-TGFα. Scatchard analysis showed that a single class of high-affinity binding sites is present on the granulosa cells (Kd 0·23 ± 0·009 nm). However, the number of binding sites altered during follicular maturation with a significant decline in the most mature follicle. These results go some way to explaining the basis for the changing sensitivity of avian granulosa cells to EGF/TGFα stimulation as they mature. In addition, the gonadotrophins, LH and FSH, increased the number of receptors in cultured granulosa cells and may therefore partially influence folliculogenesis and steroidogenesis through this route.
Journal of Endocrinology (1996) 149, 171–179
Influence of nutrition on hepatic IGF-I mRNA levels and plasma concentrations of IGF-I and IGF-II in meat-type chickens
Authors: Kita K , Tomas F M , Owens P C , Knowles S E , Forbes B E , Upton Z , Hughes R , Ballard F J 
Published: December 2004

Abstract
We have examined the influence of nutrition on plasma IGF-I, IGF-II and IGF-binding protein (IGFBP) levels and on hepatic IGF-I gene expression in young meat-type chickens. Plasma IGF concentrations were measured by using RIA with recombinant chicken IGFs as standards.
In chickens fed the control diet containing 200 g/kg dietary protein ad libitum for 7 days, plasma IGF-I concentrations increased significantly from those found in the initial control group. Food restriction for either 4 or 7 days decreased plasma IGF-I by 30% from the initial control. When chickens were refed ad libitum for 3 days after 4 days of restricted feeding, plasma IGF-I levels recovered to those of the control birds fed ad libitum. In chickens eating a low protein diet (100 g/kg protein), the plasma IGF-I tended to be lowered but the decrease was not significant. Although the intensity of IGF-I and β-actin mRNA bands protected in the RNase protection assay was changed by nutrition, no statistical effect of nutrition on the ratio of IGF-I to β-actin was observed. The nutritional treatments had no effect on plasma IGF-II concentrations.
Western ligand blot and chromatographic analyses were used to investigate the influence of nutrition on IGFBP profiles. Both IGF-I and IGF-II ligands in the Western ligand blot revealed the most intense binding at 30 kDa for plasma obtained from chickens with restricted food intake. The 30 kDa band also appeared at a lower intensity in the group fed a low protein diet but not in any other groups. These observations were confirmed by neutral gel chromatography. The chicken IGF-II ligand revealed an intensely labelled band corresponding to 75 kDa and this was not affected by nutrition.
IGF-I and IGFBP concentrations in the plasma of young broiler chickens were influenced by nutritional state but IGF-II concentrations were not. The lack of a response in circulating IGF-II levels may have been due to the presence of high concentrations of a 75 kDa specific binding protein which did not respond to nutrition in this experiment.
Journal of Endocrinology (1996) 149, 181–190
Expression of IGF-I and IGF-binding protein genes in cirrhotic liver
Authors: Ross R J M , Chew S L , D'Souza Li L , Yateman M , Rodriguez-Arnao J , Gimson A , Holly J , Camacho-Hubner C 
Published: December 2004

Abstract
The liver plays a central role in the IGF-I axis producing the majority of circulating hormone and some of its binding proteins (IGFBPs). Cirrhosis of the liver is characterised by changes in IGF-I and IGFBPs associated with liver fibrosis and regeneration. We have studied steady state levels of mRNA for the genes in the IGF-I axis in normal and cirrhotic human liver, localised the most highly expressed gene, IGFBP-1, and measured circulating IGFBP-3 by radioimmunoassay (RIA), IGFBP-2 and IGFBP-3 by Western ligand blot (WLB), and protease activity for IGFBP-3 in cirrhotic patients. Messenger RNA for IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 was detectable by Northern blotting in normal and cirrhotic liver although there was considerable variation in expression. IGFBP-2 and IGFBP-3 tended to be more highly expressed in cirrhotic liver and IGFBP-1 was more highly expressed in normal liver, although there were no significant differences. In normal liver, in situ hybridisation localised IGFBP-1 to hepatocytes. In cirrhotic liver the regenerating nodules showed expression of IGFBP-1 while there was none in fibrotic tissue. Circulating IGFBP-3 levels were low as measured by RIA and WLB but protease activity was only found in one patient. IGFBP-2 levels, assessed by WLB, were similar to the normal serum pool. Our data show that key mRNAs involved in the IGF-I axis continue to be expressed in cirrhotic liver despite end stage liver disease. The low levels of IGFBP-3 do not appear to be due to reduced gene transcription or increased protease activity.
Journal of Endocrinology (1996) 149, 209–216
Localization and distribution of angiotensin II in the rat epididymis
Authors: Zhao W , Leung P Y , Chew S B Cheng , Chan H C , Wong P Y D 
Published: December 2004

Abstract
The localization and distribution of angiotensin II (Ang II) in the rat epididymis was studied using immunohistochemical and RIA techniques. The immunohistochemical results showed that Ang II-like immunoreactivity progressively increased along the length of the rat epididymis (cauda>corpus>>caput) and was predominately localized in the basal region of the epididymal epithelium. Occasionally, immunostaining of lighter intensity was also found in the apical region. The concentration of Ang II in cultured rat cauda epididymal epithelial cells was further measured by RIA. In addition to that found in cultured epithelial cells, Ang II activity was also detected in the culture medium, suggesting a secretory role of the epithelium. These findings suggest that Ang II could be derived locally from epididymal epithelium and that it could play a role in local regulation of epithelial transport and, possibly, in the maintenance of sperm function as well, by exerting its paracrine and/or autocrine effect in various regions of the epididymis.
Journal of Endocrinology (1996) 149, 217–222
The expression of transforming growth factor-β by cultured chick growth plate chondrocytes: differential regulation by 1,25-dihydroxyvitamin D3
Authors: Farquharson C , Law A S , Seawright E , Burt D W , Whitehead C C 
Published: December 2004

Abstract
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and transforming growth factor-β (TGF-β) are both important regulators of chondrocyte growth and differentiation. We report here that 1,25(OH)2D3 differentially regulates the expression of the genes for TGF-β1 to -β3 and the secretion of the corresponding proteins in cultured chick chondrocytes. Confluent growth plate chondrocytes were serum-deprived and cultured in varying concentrations of 1,25(OH)2D3. Cells were assayed for TGF-β mRNA and conditioned medium was assayed for TGF-β activity and isoform composition. Active TGF-β was only detected in 10−8m 1,25(OH)2D3-treated cultures (8·37 ng active TGF-β/mg protein). There was a significant decrease in total (latent+active) TGF-β activity in conditioned medium of 10−12 m (23·4%; P<0·05) and 10−10 m (20·7%; P<0·05) 1,25(OH)2D3-treated cultures but 10−8 m 1,25(OH)2D3 significantly increased (30·9%; P<0·01) TGF-β activity. The amounts of TGF-β1, -β2 and -β3 isoforms produced were similar in control, 10−10 or 10−12m 1,25(OH)2D3-treated cultures but the conditioned medium of 10−8 m 1,25(OH)2D3-treated cultures contained significantly higher amounts of all three isoforms. Quantification of TGF-β mRNA demonstrated differential control of TGF-β gene expression with TGF-β1 and -β3 mRNA levels reduced by all concentrations of 1,25(OH)2D3 examined (10−8, 10−10 and 10−12 m) whilst TGF-β2 mRNA concentrations were elevated. Our results indicated that 1,25(OH)2D3 regulates chick growth plate chondrocyte TGF-β secretion and mRNA expression in a concentration-dependent and isoform-specific manner. This interaction may be important in the regulation of chondrocyte metabolism and endochondral bone growth.
Journal of Endocrinology (1996) 149, 277–285
1,25-Dihydroxyvitamin D3 increases the sensitivity of human renal carcinoma cells to tumor necrosis factor α but not to interferon α or lymphokine-activated killer cells
Authors: Yacobi R , Koren R , Liberman U A , Rotem C , Wasserman L , Ravid A 
Published: December 2004

Abstract
Renal cell carcinoma is a chemotherapy-resistant tumor which is relatively responsive to immunotherapy. Immunotherapeutic regimes employ interferons or interleukin 2 with or without lymphokine-activated killer cells. Secondary cytokines, induced by interleukin 2 or interferon, may have an important impact on their anti-neoplastic activity. Notable among them is tumor necrosis factor (TNFα). We assessed the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the susceptibility of the human renal cell carcinoma cell line SK-RC-29 to the cytotoxic and cytostatic actions of TNFα, interferon a and lymphokine-activated killer cells. Using uptake of the vital dye neutral red as an indicator of viable cell number, we found that addition of 1,25(OH)2D3 (100 nm) to TNFα (30 ng/ml)-treated cultures resulted in a 2·6 ± 0·2-fold (mean ± s.e.) increase in the cytotoxic effect of the cytokine. The potentiating effect of 1,25(OH)2D3 was dose-dependent, and significant at concentrations equal to or higher than 10 nm. Another dihydroxylated vitamin D metabolite, 24,25(OH)2D3, had no effect on TNFα action. The cytotoxic effect of TNFα increased whereas the potentiation by 1,25(OH)2D3 decreased with cell density in culture. 1,25(OH)2D3, in contrast to its potentiating effect on TNFα action, did not modulate the cytostatic effect of interferon α or the susceptibility of SK-RC-29 to killing by lymphokine-activated killer cells. The findings reported here may explain some of the in vivo anti-tumor activity of 1,25(OH)2D3 and provide a rationale for the employment of active vitamin D analogs during immune anti-cancer therapy.
Journal of Endocrinology (1996) 149, 327–333
Regulation of cartilage glycosaminoglycan synthesis in the rainbow trout, Oncorhynchus mykiss, by 3,3′,5-tri-iodo-l-thyronine and IGF-I
Authors: Takagi Y , Th Björnsson B 
Published: December 2004

Abstract
The actions of 3,3′,5-tri-iodo-l-thyronine (T3) and recombinant human IGF-I (rhIGF-I) as well as their interaction on cartilage growth in rainbow trout (Oncorhynchus mykiss) were examined. Uptake of 3H-methyl thymidine and 35S-sulfate by isolated branchial cartilage was measured as a marker for chondrocyte proliferation and sulfated glycosaminoglycan synthesis respectively. When T3 (1·0 μg/g) was injected intraperitoneally, plasma T3 levels reached a transient peak after 1 day and decreased rapidly thereafter. Sulfate and thymidine uptake were not affected by T3 at 1 and 3 days post-injection, but at 6 days post-injection both were significantly higher in T3injected fish than those in controls. The stimulatory effects of a T3 injection on sulfate and thymidine uptake were dose-dependent over the range of 0·01, 0·1 and 1·0 μg/g. In vitro exposure of cartilage to T3 (0·075, 0·75, 7·5, 75 and 750 nm) for 6 days resulted in dose-dependent stimulation of sulfate uptake, with a maximum response at 7·5 nm and higher. T3 exposure (7·5 nm) for 2 or 3 days also increased sulfate uptake, but only slightly. Thymidine uptake was not clearly affected by T3. In vitro addition of rhIGF-I (0·075, 0·75 and 7·5 nm) increased sulfate uptake, but not thymidine uptake, dose-dependently. Compared with T3, rhIGF-I induced a greater maximum level of sulfate uptake: at 7·5 nm rhIGF-I increased the uptake 17-fold whereas T3 increased the uptake fourfold. When T3 (0·075, 0·75 or 7·5 nm) and rhIGF-I (0·1 or 1·0 nm) were added together, stimulative actions of T3 on sulfate uptake were largely additive to those of rhIGF-I. The results indicate that T3 as well as IGF-I are important modulators of sulfated glycosaminoglycan synthesis in rainbow trout cartilage.
Journal of Endocrinology (1996) 149, 357–365