bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of long-term β-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the β-cells to hyperglycaemia in vivo
Authors: Svensson C. , Sandler S. , Hellerström C. 
Published: December 2008

ABSTRACT
Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet β-cells from these two mouse strains, with different sensitivities of their β-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5·6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5·6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1·7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l. Insulin mRNA content was increased in islets cultured in 28 or 56 mmol glucose/l from both mouse strains. Glucose metabolism showed no differences in the rates of glucose oxidation, however, in islets cultured in 56 mmol glucose/l the utilization of glucose was increased in both BL/6J and BL/KsJ animals. There were no differences in DNA content in islets cultured at different glucose concentrations, suggesting no enhancement of cell death.
The present study indicates that, irrespective of genetic background, murine β-cells can adapt to very high glucose concentrations in vitro without any obvious signs of so-called glucotoxicity. Previously observed signs of glucotoxicity in vivo in BL/KsJ islets appear not to be related only to glucose but rather to an additional factor in the diabetic environment.
Journal of Endocrinology (1993) 136, 289–296
The effect of basic fibroblast growth factor on the growth and function of human thyrocytes
Authors: Taylor A. H. , Millatt L. J. , Whitley G. StJ. , Johnstone A. P. , Nussey S. S. 
Published: December 2008

ABSTRACT
Basic fibroblast growth factor (bFGF) was quantitated in human primary thyrocyte cultures and thyroid cell lines produced by transfection with pSV3neo. Immunoreactive-bFGF (ir-bFGF) bound to heparin–Sepharose affinity columns eluted with 1·8–2·0 mol NaCl/l and had a molecular weight of approximately 17 000. Recombinant human bFGF in the presence of 5% serum increased the growth of transfected human thyrocytes but not the growth of primary human thyrocytes. Preincubation of cells with up to 100 μg bFGF/l potentiated TSH-stimulated cAMP release from the transfected cells but inhibited release from primary human thyroid cultures. bFGF may be an important modulator of thyroid cell function and growth.
Journal of Endocrinology (1993) 136, 339–344
Release of bioactive ACTH by perifused human placenta at early and late gestation
Authors: Waddell B. J. , Burton P. J. 
Published: December 2008

ABSTRACT
This study assessed whether bioactive ACTH is released by the human placenta during perifusion in vitro at early and late gestation. Human placental villous fragments from early (8–12 weeks) and late (38–40 weeks) gestation were perifused at a constant rate for 6·5 h. To assess ACTH-like bioactivity released by this tissue, the perifusion effluent was redirected through adjacent chambers containing freshly dispersed adrenocortical cells obtained from adult rats. Baseline secretion of corticosterone by these adrenocortical cells averaged 95±26 (s.e.m.) fmol/min, and this increased at least fivefold (P <0·01, two-way ANOVA) in response to placental effluent at early and late gestation. The magnitude of this increase, expressed as a percentage of the maximal response to a subsequent stimulus with ACTH(1–24), was similar for placentas obtained at early (41 ± 12% of maximal response) and late (42 ± 17%) gestation. Immunoreactive (I)-ACTH was readily detectable in placental effluent from all preparations (5·5±2·3 fmol/min per g tissue), and there was no apparent difference with stage of gestation.
To determine whether all of the ACTH-like bioactivity released by the placenta was attributable to I-ACTH, a second series of placental/adrenal perifusions was conducted. In these, I-ACTH was selectively removed from placental effluent by immunoneutralization, and the residual bioactivity measured. Immunoneutralization involved preincubation of placental effluent with ACTH antiserum (1:100), and preincubation with normal rabbit serum (NRS) served as a control. Preincubation with ACTH antiserum, but not with NRS, resulted in a marked reduction in ACTH-like bioactivity present in placental effluent at both early (P <0·01, paired t-test) and late (P <0·05) gestation. This inhibition was significantly more effective (P <0·05, unpaired t-test) at early than at late gestation.
Overall, these data establish that the human placenta can release bioactive ACTH-like activity at both early and late gestation, and that much, but not all, of this bioactivity is directly attributable to I-ACTH. These findings clearly demonstrate a potential role for placental ACTH in directly influencing the maternal and/or fetal hypothalamic-pituitary-adrenal axes during human pregnancy.
Journal of Endocrinology (1993) 136, 345–353
Sex steroids affect glucocorticoid response to chronic inflammation and to interleukin-1
Authors: Da Silva J. A. P. , Peers S. H. , Perretti M. , Willoughby D. A. 
Published: December 2008

ABSTRACT
The influence of gender and sex hormones upon both the hypothalamic-pituitary-adrenal (HPA) axis and the immune and inflammatory responses is well recognized, but it is not clear to what extent the two effects are interdependent. We have investigated this interaction using a chronic inflammation model. Corticosterone levels were measured in mature BALB/c male and female mice, which were intact, sham-operated or gonadectomized. No significant differences were found between groups in baseline corticosterone, but systemic inflammation (cotton-induced granulomas) resulted in stimulation of the HPA axis in a reproducible pattern. Corticosterone levels were higher in sham-operated females than in males, but gonadectomy had opposing effects in the two genders, resulting in reduced levels in females but significantly increased levels in males. A similar pattern emerged after stimulation by ether exposure or injection of interleukin-1β. In the chronic inflammatory model, replacement of ovariectomized females with physiological levels of progesterone restored a response similar to that of intact females. Physiological levels of 5α-dihydrotestosterone prevented the increase in corticosterone levels caused by castration in males and also resulted in reduced corticosterone levels in sham-operated females. Oestradiol treatment did not affect corticosterone levels. Release of interleukin-1 by peritoneal macrophages from intact and gonadectomized mice with chronic inflammation followed a similar pattern, females releasing more than males. These data suggest a complex inter-relationship between sex steroids, inflammatory stimuli and the HPA axis, such that females have a greater tendency than males to generate activating signals and in addition have a greater sensitivity to such factors.
Journal of Endocrinology (1993) 136, 389–397
Effects of growth hormone and thyroxine on kidney insulin-like growth factor-I and renal growth in hypophysectomized rats
Authors: Marshall S. M. , Flyvbjerg A. , Jørgensen K. D. , Weeke J. , Ørskov H. 
Published: December 2008

ABSTRACT
The effects of treatment for 11 days with human growth hormone (hGH; 140 μg/day), thyroxine (T4; 3 μg/day) and hGH + T4 on renal growth and content of insulin-like growth factor-I (IGF-I) in hypophysectomized rats have been compared with saline-treated hypophysectomized animals and intact control animals. Right kidney weight and kidney weight/body weight ratio remained low in the saline-treated group (313±9 vs 694±28 mg in controls on day 11, P<0·001 and 3·4±0·12 × 10−3 vs 4·2±0·10× 10−3, P< 0·005 respectively). In T4- and hGH-treated animals, kidney weight gain was similar (to 420 ± 14 and 450±22 mg on day 11 respectively, P>0·05), whilst the increase was greater in the group given hGH + T4 (to 572 ±34 mg, P< 0·001 compared with hGH- and T4-treated groups). The kidney weight/body weight ratio became normal in the T4- and hGH + T4-treated animals but remained low in the hGH-treated group. The renal content of IGF-I was low in the salinetreated animals throughout the study (92±10 ng/g on day 11 vs 219±8 ng/g in control animals, P< 0·001), but increased to a maximum of 88% above baseline on day 1 in the group given T4. In the hGH-and hGH + T4-treated groups, renal IGF-I concentration rose to a peak of 317% above baseline on days 2 to 4, then fell to the values seen in control animals on day 11 (hGH: 242±18 ng/g; hGH + T4: 320 ± 41 ng/g; controls: 219 ± 8 ng/g; P> 0·05 for all comparisons). Thus treatment with hGH or T4 results in similar kidney weight gain, despite a greater rise in the renal concentration of IGF-I in the hGH-treated animals. Treatment with both hGH + T4 leads to an increase in the renal concentration of IGF-I similar to that seen with hGH treatment alone, but a larger increase in kidney weight, suggesting that T4 does not stimulate renal growth via the IGF-I pathway and that growth promotion by hGH and T4 is additive.
Journal of Endocrinology (1993) 136, 399–406
The human chorionic gonadotrophin-induced inflammationlike response is enhanced in macrophage-depleted rat testes
Authors: Bergh A. , Damber J.-E. , van Rooijen N. 
Published: December 2008

ABSTRACT
Liposome-entrapped dichloromethylene diphosphonate (Cl2MDP) was injected locally into the right testes of adult rats in order to deplete testicular macrophages. The number of testicular macrophages in the treated testes was reduced by at least 90% at 7 and 14 days after treatment. Unilaterally testicular macrophage-depleted animals were treated with 100 IU human chorionic gonadotrophin (hCG) subcutaneously and the inflammatory response was compared in the macrophage-depleted and intact contralateral testis. Four hours after hCG treatment, intratesticular testosterone was similarly increased in intact and macrophage-depleted testes. In macrophage-depleted testes there was a large increase in the number of leukocytes in testicular blood vessels and numerous leukocytes had migrated into the interstitial tissue. This response was greater than in the intact contralateral testis. It was concluded that testicular macrophages are probably not the origin of the inflammatory mediator secreted in the rat testis after hCG treatment. On the contrary, it appears that testicular macrophages may secrete factors inhibiting hCG-induced testicular inflammation.
Journal of Endocrinology (1993) 136, 415–420
Serum and urinary concentrations of sex hormones and genital swelling during the menstrual cycle of the gibbon
Authors: Nadler R. D. , Dahl J. F. , Collins D. C. 
Published: December 2008

ABSTRACT
The relationship between sex hormone concentrations and female genital swelling during the menstrual cycle in the monogamous gibbon was comparable with that of polygamous female primates, such as the chimpanzee, which live in multimale groups and have larger swellings. The data, therefore, support the hypothesis proposed by C. R. Carpenter more than 50 years ago, that the gibbon's genital swelling, like that of other female primates, reflects basic physiological processes associated with progress of the menstrual cycle. Genital swelling increased during the follicular phase with increasing concentrations of oestradiol and oestrone glucuronide, reached maximal swelling in association with the mid-cycle peaks in the oestrogens and LH and began detumescence with the initial increases in progesterone during the luteal phase. The data also suggest that the menstrual cycle of the gibbon is shorter than previously reported, since cycles of 19–22 days exhibited hormone patterns that are consistent with ovulation. The genital swelling of the female gibbon is a useful marker for monitoring progress of the menstrual cycle and the presumptive time of ovulation.
Journal of Endocrinology (1993) 136, 447–455
The action of LH-releasing hormone and five analogues on oestradiol, oxytocin and vasopressin secretion by bovine granulosa cells in culture
Authors: Sirotkin A. V. , Nitray J. , Nikolajev S. V. , Burov S. V. 
Published: December 2008

ABSTRACT
The release of oxytocin, arginine-8-vasopressin and oestradiol-17β by bovine granulosa cells in culture was analysed either with or without LH-releasing hormone (LHRH), its agonists (cyclo [Pro1dPhe6] LHRH and des 1–3, 10[dAla6] LHRH) or antagonists ([dPhe2dPhe6] LHRH, [dPhe2dPhe(NH2)6] LHRH or cyclo [Pro1dPhe2dPhe6] LHRH). All preparations used stimulated granulosa oxytocin and oestradiol secretion. Vasopressin release was significantly increased after all treatments with LHRH antagonists, but not after LHRH or its agonists.
Our observations demonstrated a direct influence of LHRH and its analogues on the secretion of oestrogen and nonapeptide hormones by bovine granulosa cells. A comparison of the effects of LHRH, its agonists and antagonists suggests that the action of these peptides at the hypophysial and ovarian level is relatively independent.
Journal of Endocrinology (1993) 136, 491–496
Interaction between insulin and thyroid hormone in rat pituitary tumour cells: insulin attenuates tri-iodothyronine-induced growth hormone mRNA levels
Authors: Prager D. , Weber M. M. , Gebremedhin S. , Melmed S. 
Published: December 2008

ABSTRACT
Insulin has previously been shown to inhibit basal and stimulated rat GH (rGH) secretion as well as basal GH transcription in rat pituitary cells. The effect of physiological doses of insulin on tri-iodothyronine (T3)-stimulated GH mRNA levels in rat pituitary tumour cells was therefore examined. Insulin (7 nmol/l) suppressed T3-stimulated GH mRNA levels in GC and GH3 rat pituitary tumour cells by 58%. This inhibitory effect of insulin on T3-stimulated GH mRNA levels was already present after 24 h of treatment, and persisted for at least 48 h after insulin treatment was withdrawn. The effect of insulin on GH mRNA was selective, as rat prolactin mRNA was stimulated by insulin and T3 in the same cells. Treatment of cells with cycloheximide (10 μmol/l) did not alter the attenuation of GH mRNA levels by insulin, indicating that the insulin effect is independent of new protein synthesis. When de-novo mRNA synthesis was blocked with actinomycin D (4 μg/ml) for up to 7 h, an additional decrease in the relative amount of GH mRNA levels was observed after 24, 48 and 72 h of insulin treatment, indicating that an effect of insulin on GH mRNA stability is likely. The results show that physiological doses of insulin selectively attenuate the stimulatory effect of T3 on GH mRNA levels. This suppressive effect of insulin occurs independently of protein synthesis and is presumably mediated both at a transcriptional and post-transcriptional level.
Journal of Endocrinology (1993) 137, 107–114
Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development
Authors: Flint D. J. , Gardner M. J. 
Published: December 2008

ABSTRACT
Neonatal female rats were treated for 3 weeks (short term) or 8 weeks (long term) with antiserum to rat GH (anti-rGH) with or without replacement therapy with recombinant bovine GH (bGH). Body weight gain and tail length were significantly suppressed within the first 3 weeks and were even more markedly suppressed when treatment was continued for 8 weeks. When treatment was stopped in short-termtreated animals the rate of body weight gain recovered, although without evidence of catch-up growth. These effects were all normalized by concurrent treatment with bGH. Long-term anti-rGH treatment caused a profound reduction (80%) in the number of differentiated adipocytes in two internal fat depots, whilst the subcutaneous depot was only moderately affected (20%). In contrast, after recovery from short-term treatment with anti-rGH, the internal depots were only marginally decreased in both weight and adipocyte numbers, whereas the subcutaneous depot was actually doubled in size compared with controls, due entirely to an increase in the number of differentiated adipocytes. These data clearly demonstrate for the first time that GH is required for the differentiation of adipocytes in vivo. In addition, the results demonstrate distinct effects at different anatomical sites and suggest that GH may be one factor responsible for the differences described in numerous metabolic parameters and hormonal sensitivities of adipose tissue derived from different locations within the body.
Journal of Endocrinology (1993) 137, 203–211
Effects of recombinant human activin A on growth hormone secretion by human somatotrophinomas in vitro
Authors: Daniels M. , Harris P. E. , James R. A. , Turner S. J. , Dewar J. H. , Kendall-Taylor P. 
Published: December 2008

ABSTRACT
Activin A is a homodimer of inhibin βA subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The βA subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques.
Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0·01–10 nmol recombinant human activin A/1 followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12–63% above control values during treatment with 0·01–10 nmol activin A/1, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0·01–1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these.
These data demonstrate that activin A stimulates basal GH secretion from the cells of some, but not all, human somatotrophinomas in vitro. Pretreatment with the peptide may also partially block GRF-stimulated GH release from GRF-responsive somatotrophinoma cells. The importance of these actions in the pathophysiological regulation of human somatotrophinomas remains to be determined.
Journal of Endocrinology (1993) 137, 329–334
Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant in normal female rats
Authors: Tomas F. M. , Knowles S. E. , Chandler C. S. , Francis G. L. , Owens P. C. , Ballard F. J. 
Published: December 2008

ABSTRACT
Administration of IGF-I over a 14-day period to growing female rats via s.c. implanted osmotic pumps led to an increased body weight gain, an improved N retention and a greater food conversion efficiency. The effects were dose-dependent, with the highest daily dose tested, 278 μg/day, producing 18–26% increases in these measurements. LR3IGF-I, a variant of human IGF-I that contains an amino terminal extension peptide as well as glutamate-3 replaced by arginine and exhibits very weak binding to IGF-binding proteins, was substantially more potent than the natural growth factor, in that 44 μg/day of this peptide produced similar effects to the high IGF-I dose. Organ weight and carcass composition measurements showed that the two IGF peptides generally maintained body proportions at those existing when the experiment began. Muscle protein synthesis and myofibrillar protein breakdown were both slightly increased by IGF treatment, so that the observed improvement in N retention could not be explained through protein accretion rates calculated from these measures. Infusion of human GH at a dose of 213 μg/day did not stimulate body growth. This investigation establishes that IGF peptides stimulate the growth of normal growing animals, with IGF-I variants that bind less well to IGF-binding proteins being more active than IGF-I.
Journal of Endocrinology (1993) 137, 413–421
Effects of chronic corticotrophin treatment on aldosterone metabolism in the rat
Authors: Abayasekara D. R. E. , Onyezili N. I. , Whitehouse B. J. , Laird S. M. , Vinson G. P. 
Published: December 2008

ABSTRACT
Chronic treatment with high doses of ACTH leads to marked reduction in aldosterone biosynthesis and secretion both in vivo and in vitro. In contrast, it has been reported that peripheral plasma aldosterone levels may be elevated following prolonged ACTH treatment. The present study attempts to determine the reason(s) for this apparently paradoxical finding. ACTH treatment (40 μg/100 g body weight) of male Sprague–Dawley rats for 7 days caused a decrease of more than 90% in aldosterone secretion into the adrenal vein in vivo and aldosterone production by intact adrenal capsules incubated in vitro. In contrast, peripheral plasma aldosterone levels appeared to be increased when measured by radioimmunoassay using two different polyclonal antibodies (antibody 1 (AB1) raised against aldosterone-3-carboxymethyloxime–bovine serum albumin (BSA) and antibody 2 (AB2) raised against aldosterone-21-hemisuccinate–BSA). However, when a highly specific monoclonal antibody (raised against aldosterone-3-carboxymethyloxime–BSA and showing low cross-reactivity to aldosterone metabolites) was used, peripheral plasma aldosterone levels appeared to be reduced in ACTH-treated rats. Following chromatographic fractionation of peripheral plasma, significantly more material with aldosterone-like immunoreactivity, but which was less polar than authentic aldosterone in chromatographic mobility, was detected in the fractions using antibodies AB1 and AB2. The absence of this material from fractions of adrenal vein plasma leads us to infer that this material is generated in the peripheral circulation, probably as a result of hepatic metabolism. In addition, the overall metabolic clearance rate (MCR) of [3H] aldosterone was found to be significantly decreased following prolonged ACTH treatment. We conclude that the seemingly discrepant findings with regard to the effects of chronic ACTH treatment on peripheral plasma aldosterone levels and the secretion of aldosterone in vivo can be reconciled by (1) the changes in the overall MCR of aldosterone and (2) the generation of increased quantities of aldosterone metabolites such as 5α-dihydroaldosterone and 3α,5β-tetrahydroaldosterone which show significant cross-reactivity with some aldosterone antibodies.
Journal of Endocrinology (1993) 137, 445–455