bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin-like growth factor (IGF)-binding protein release by human fetal fibroblasts: dependency on cell density and IGF peptides
Authors: Hill D. J. , Camacho-Hubner C. , Rashid P. , Strain A. J. , Clemmons D. R. 
Published: December 2008

ABSTRACT
Insulin-like growth factors (IGFs) are bound to specific binding proteins in extracellular fluids in vivo and when released by cells in vitro. One class of binding protein (IGF-BP), a peptide of 26 kDa purified from amniotic fluid, has been shown to modulate IGF bioactivity on isolated human fibroblasts. We have determined the factors that control release of IGF-BP from monolayers of human fetal fibroblasts using a radioimmunoassay, and have compared this with the effects of these factors on the release of IGF-I and -II. Separation of cell-conditioned cultured medium on SDS-PAGE, and subsequent immunoblotting with antibody against IGF-BP showed that fibroblasts released a single species of immunoreactive protein of an estimated molecular weight of 30 kDa. This was not the predominant binding protein released by cells since major bands of approximately 42 kDa and 39 kDa were visualized following separation by SDS-PAGE and ligand blotting with 125I-labelled IGF-I. The 30 kDa IGF-BP was released in parallel with radioimmunoassayable IGF-I and -II over 48 h. However, a significant inverse correlation was found between the release of IGF-BP, IGF-I, IGF-II and cell density. The exposure of fibroblasts to 1·3 nmol/l or greater of IGF-I or -II caused a significant release of IGF-BP. Maximum release was seen in sparse cultures with little or no release from confluent cultures. IGF-I and -II were approximately equipotent with a fourfold increase in IGF-BP release at 19·7 nmol/l. Insulin caused a release of IGF-BP and IGF-I and -II from fibroblasts at supraphysiological concentrations (16·7 nmol/l) which again was maximal on sparse cell cultures. Increases in IGF-BP, IGF-I and -II release were also found in the presence of human placental lactogen (23·3 nmol/l), but human GH, epidermal growth factor, fibroblast growth factor and platelet-derived growth factor were without effect. The results show that human fetal fibroblasts released an IGF-BP immunologically similar to that seen in amniotic fluid together with IGF-I and -II, that IGF-BP release was enhanced by exogenous addition of IGF peptides, and that the release of all three peptides was a property of sparsely plated, rapidly growing cells. These findings strengthen the hypothesis that the cellular expression of IGF-binding proteins may represent an important level of control in IGF physiology.
Journal of Endocrinology (1989) 122, 87–98
Peripheral metabolism of [35S]parathyroid hormone in vivo: influence of alterations in calcium availability and parathyroid status
Authors: Bringhurst F. R. , Stern A. M. , Yotts M. , Mizrahi N. , Segre G. V. , Potts J. T. 
Published: December 2008

ABSTRACT
Parathyroid hormone (PTH) is rapidly metabolized, mainly by liver and kidney, to smaller fragments that are believed to be biologically inactive. The significance of this peripheral metabolism in the overall actions of PTH is unclear. Generation of circulating biologically active amino-terminal PTH fragments during metabolism in vivo has been suggested by certain observations in vitro, and what are believed to be amino-terminal fragments may be detectable in blood under pathological circumstances in vivo (such as renal failure and coexistent hyperparathyroidism) when highly sensitive assays are employed. We recently reported, however, that administration to normal rats of [35S]bovine PTH ([35S]bPTH) directly labelled at amino-terminal methionines, followed by high-resolution chromatographic analysis of extracted [35S]peptides, does not result in appearance of radioactive amino-terminal fragments in blood, even when the tracer is continuously infused to near-physiological plasma concentrations. We have now employed these techniques to address a second question regarding hormonal metabolism: is hormonal metabolism modified during metabolic perturbations such as changing calcium availability or altered levels of calciotrophic hormones? Metabolism of [35S-Met]bPTH (900 Ci/mmol), either alone or together with [3H-Pro]bPTH, however, did riot lead to alterations in the rate of hormonal clearance nor to detectable circulating amino-terminal fragments, either in calcium-deprived or thyroparathyroidectomized rats or when animals were first rendered intoxicated with vitamin D or maintained on a high calcium intake. Likewise, tissue localization and specific cleavage patterns of intact hormone in liver or kidney were all unaltered by these various manoeuvres. We conclude that regulation of peripheral metabolism of PTH does not exert important physiological control over the concentration of circulating biologically active PTH and that active amino-terminal fragments of the hormone are not released into blood even under circumstances of calcium deprivation or hypocalcaemia.
Journal of Endocrinology (1989) 122, 237–245
Effect of sodium intake on phosphoinositides and inositol trisphosphate response to angiotensin II, K+ and ACTH in rat glomerulosa cells
Authors: Underwood R. H. , Menachery A. I. , Williams G. H. 
Published: December 2008

ABSTRACT
To assess the impact of sodium intake on the adrenal phosphoinositide system, rats were maintained on a low or normal salt diet for 5 days, and glomerulosa cell preparations (2×105 cells) were stimulated by angiotensin II (AII; 10 nmol/l), potassium (K+; 8·7 mmol/l) or ACTH (0·1 nmol/l) for 0, 2, 4, 6, 12, 15 and 60 s. Levels of phosphatidylinositol (PtdIns), phosphatidylinositol 4-phosphate (PtdIns 4-P), phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3)+inositol3) + inositol 1,3,4-trisphosphate (Ins 1,3,4-P3) were assayed by a microspectrophotometric procedure. Non-stimulated levels of PtdIns, PtdIns 4-P, PtdIns 4,5-P2 and Ins 1,4,5-P3 (+Ins 1,3,4-P3) (means ± s.e.m.; n = 36) in cells from rats on the low Na+ intake were 580 ± 6·5, 187 ± 2·6, 82 ± 3 and 95 ± 1·2 pmoler incubate respectively, indistinguishable from those observed in rats on a normal Na+ intake, except for the significantly (P<0·025) greater Ptdlns 4,5-P2 level. In response to AII stimulation, all four compounds showed an earlier and greater peak response when cells were obtained from animals on a low rather than a high sodium intake. All values had returned to control levels by 12–15 s, regardless of the level of sodium intake. In contrast, with K+ stimulation there were no differences in the peak response of cells from rats on the two dietary intakes, but there was a shift of the peak to a longer time-interval (6 versus 8 s) in animals maintained on a low sodium intake. In addition, PtdIns 4,5-P2 did not return to control levels in cells obtained from animals on a low sodium intake. However, the most striking differences were observed in response to ACTH. In animals maintained on a normal sodium intake, there were no changes in any of the four compounds. In contrast, there was a sharp increase in all four substances in response to ACTH when the cells were obtained from animals on a low sodium intake, with peak levels occurring at 8 s, similar to that observed with potassium. Thus, changes in the response pattern of the phosphoinositides may mediate the altered adrenal responsiveness to AII and ACTH with sodium restriction.
Journal of Endocrinology (1989) 122, 371–377
Reduced responses of prolactin and catecholamine to stress in the lactating rat
Authors: Higuchi T. , Negoro H. , Arita J. 
Published: December 2008

ABSTRACT
Prolactin, GH, TSH, adrenaline and noradrenaline responses to the stress of immobilization were compared between lactating and non-lactating dioestrous rats. The concentrations of GH in plasma were reduced to a similar degree by the immobilization of lactating and non-lactating rats, and TSH levels were unchanged in both groups. The increases in plasma concentrations of adrenaline and noradrenaline induced by stress were significantly smaller in lactating than in non-lactating rats. Immobilization caused a marked increase in prolactin levels in the plasma of non-lactating rats but no increase in lactating rats. These changes may help to save energy and maintain milk production during the period of lactation.
Journal of Endocrinology (1989) 122, 495–498
Seasonal and steroid-dependent effects on the modulation of LH secretion in the ewe by intracerebroventricularly administered β-endorphin or naloxone
Authors: Horton R. J. E. , Francis H. , Clarke I. J. 
Published: December 2008

ABSTRACT
The natural opioid ligand, β-endorphin, and the opioid antagonist, naloxone, were administered intracerebroventricularly (i.c.v.) to evaluate effects on LH secretion in ovariectomized ewes and in ovariectomized ewes treated with oestradiol-17β plus progesterone either during the breeding season or the anoestrous season. Ovary-intact ewes were also studied during the follicular phase of the oestrous cycle. Jugular blood samples were taken at 10-min intervals for 8 h and either saline (20–50 μl), 100 μg naloxone or 10 μg β-endorphin were injected i.c.v. after 4 h. In addition, luteal phase ewes were injected i.c.v. with 25 μg β-endorphin(1–27), a purported endogenous opioid antagonist.
In ovariectomized ewes, irrespective of season, saline and naloxone did not affect LH secretion, but β-endorphin decreased the plasma LH concentrations, by reducing LH pulse frequency. The effect of β-endorphin was blocked by administering naloxone 30 min beforehand. Treating ovariectomized ewes with oestradiol-17β plus progesterone during the breeding season reduced plasma LH concentrations from 6–8 μg/l to less than 1 μg/l. In these ewes, saline did not alter LH secretion, but naloxone increased LH pulse frequency and the plasma concentrations of LH within 15–20 min. During anoestrus, the combination of oestradiol-17β plus progesterone to ovariectomized ewes reduced the plasma LH concentrations from 3–5 μg/l to undetectable levels, and neither saline nor naloxone affected LH secretion.
During the follicular phase of the oestrous cycle, naloxone enhanced LH pulse frequency, which resulted in increased plasma LH concentrations; saline had no effect. In these sheep, β-endorphin decreased LH pulse frequency and the mean concentrations of LH, and this effect was prevented by the previous administration of naloxone. The i.c.v. administration of β-endorphin(1–27) to luteal phase ewes did not affect LH secretion.
These data demonstrate the ability of a naturally occurring opioid peptide to inhibit LH secretion in ewes during the breeding and non-breeding seasons, irrespective of the gonadal steroid background. In contrast, whilst the gonadal steroids suppress LH secretion in ovariectomized ewes during both seasons, they only appear to activate endogenous opioid peptide (EOP)-mediated inhibition of LH secretion during the breeding season. Furthermore, these data support the notion that LH secretion in ovariectomized ewes is not normally under the control of EOP, so that naloxone has no effect.
Journal of Endocrinology (1989) 122, 509–517
Growth hormone and growth in diabetic rats: effects of insulin and insulin-like growth factor-I infusions
Authors: Carlsson L. M. S. , Clark R. G. , Skottner A. , Robinson I. C. A. F. 
Published: December 2008

ABSTRACT
The effects of streptozotocin-induced diabetes on weight gain, bone growth and GH secretion have been studied in conscious chronically cannulated male rats. In addition to the classic diabetic symptoms (hyperphagia, polydipsia, polyuria, glycosuria and hyperglycaemia), the slow body weight gain (0·95 ± 0·5 compared with 2·63 ± 0·5 g/day in non-diabetic controls) was associated with a reduction in bone growth (from 162 ± 9 to 48 ± 4 μm/day) and a reduced pituitary GH content (from 1·5 ± 0·2 to 0·6 ± 0·06 mg/gland). Serial blood sampling during the day or overnight showed that the normal male episodic GH secretory pattern was obliterated in the diabetic animals. The constant osmotic stimulation of hyperglycaemia and high fluid turnover was reflected in a significant reduction in pituitary oxytocin and arginine vasopressin (AVP) stores. Intravenous insulin infusions (67–1340 pmol/h for 4 or 7 days) caused a large initial weight gain (> 20 g in 2 days) followed by a slower increase, and stimulated tibial bone growth (to 100 ± 16 and 126 ± 8 μm/day after 4 or 7 days respectively). Insulin infusion for 7 days also increased pituitary GH content (to 1 ± 0·15 mg/gland), and the normal episodic GH secretory pattern returned. Intravenous infusions of insulin which reduced, but did not completely normalize, blood glucose levels, allowed the resumption of growth and pulsatile GH secretion. Continuous infusion of recombinant human insulin-like growth factor-I (hIGF-I) at 1110 pmol/h for 54 h also caused a large initial rise in body weight in diabetic rats (17·1 ± 1·6 compared with 7·5 ± 2·8 g in saline-infused controls) due primarily to increased fluid retention. This effect of hIGF-I occurred without any significant changes in pituitary GH, AVP, oxytocin, blood glucose or bone growth over this short-term infusion, nor was there any obvious effect on spontaneous GH secretion, monitored over the entire infusion period. We conclude that the diabetic rat is not a good model to study growth stimulation by short-term insulin or IGF-I treatments because the insulin-like effects of these peptides obscure their specific growth-promoting activities in this model.
Journal of Endocrinology (1989) 122, 661–670
Proliferation and differentiation of possible Leydig cell precursors after destruction of the existing Leydig cells with ethane dimethyl sulphonate: the role of LH/human chorionic gonadotrophin
Authors: Teerds K. J. , de Rooij D. G. , Rommerts F. F. G. , van den Hurk R. , Wensing C. J. G. 
Published: December 2008

ABSTRACT
The influence of LH levels on the proliferation and differentiation of possible Leydig cell precursors was investigated in adult rats, after the destruction of the existing Leydig cells with the cytotoxic drug ethane dimethyl sulphonate (EDS). In rats bearing a testosterone implant which prevented the rise in plasma LH levels and kept them within the normal range after the destruction of the Leydig cells, the proliferative activity of possible Leydig cell precursors still increased seven- to eightfold 2 days after EDS administration. Apparently, in this situation, locally produced factors, and not LH, may play a role in the stimulation of proliferation. The proliferative activity of the possible precursor cells could be further stimulated by treating rats with daily injections of human chorionic gonadotrophin (hCG) following EDS administration. It was concluded that the proliferative activity of possible Leydig cell precursors is probably regulated by both paracrine and endocrine factors.
Almost no Leydig cells were formed in the rats bearing a testosterone implant during the first 4 weeks after EDS administration. When these rats were treated with hCG, starting 28 days after administration of EDS, a substantial number of Leydig cells was found after 2 days, and these cells also showed 3β-hydroxysteroid dehydrogenase (3β-HSD) and α-naphtyl esterase (α-NE) activity. When hCG treatment was started at 14 or 21 days after EDS administration, some cells with the nuclear characteristics of Leydig cells were present after 2 days, but no 3β-HSD or α-NE activity could be detected. Finally, when hCG treatment was started directly after EDS administration, a considerable number of Leydig cells was found 14 days after EDS, and some of these cells already showed 3β-HSD and α-NE activity. It is concluded that precursor cells are able to develop into advanced precursor cells at normal LH levels, and that the rate of development of new Leydig cells strongly depends upon LH/hCG levels.
Journal of Endocrinology (1989) 122, 689–696
Effect of noradrenaline and γ-aminobutyric acid on the secretion of corticotrophin-releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro
Authors: Hillhouse E. W. , Milton N. G. N. 
Published: December 2008

ABSTRACT
Much controversy exists concerning the role of catecholamines in the control of ACTH secretion. In this study, noradrenaline (0·1 nmol–0·1 μmol/l) stimulated the release of both immunoreactive corticotrophin-releasing factor-41 (ir-CRF-41) and ir-arginine vasopressin (ir-AVP) from the rat hypothalamus in vitro. The stimulatory effect of noradrenaline on CRF-41 release was blocked by propranolol, whilst that on AVP release was blocked by phentolamine. γ-Aminobutyric acid (GABA; 10 nmol/l) inhibited the acetylcholine-induced release of both AVP and CRF-41 in vitro, and the effect was blocked by picrotoxin (0·1 μmol/l). Neither substance had any effect on the basal secretion of either neuropeptide. The results indicate that noradrenaline stimulates and GABA inhibits the release of both peptides from the rat hypothalamus in vitro.
Journal of Endocrinology (1989) 122, 719–723
Plasma growth hormone pattern and androgens influence the levels of corticosteroid-binding globulin in rat serum
Authors: Jansson J.-O. , Oscarsson J. , Mode A. , Ritzén E. M. 
Published: December 2008

ABSTRACT
The serum concentration of corticosteroid-binding globulin (CBG) is higher in female rats than in males. Combined hypophysectomy and gonadectomy of female rats reduced the serum concentration of CBG as measured by steady-state polyacrylamide gel electrophoresis, whereas hypophysectomy of male rats increased serum CBG. These effects were seen despite replacement therapy with thyroxine and glucocorticoids. Moreover, neither androgen nor oestrogen treatment affected the serum concentrations of CBG in hypophysectomized rats. Continuous infusions of human or bovine GH (1·4 U/kg per day), by means of osmotic minipumps for 1 week, increased serum concentrations of CBG in both hypophysectomized male and female rats. In contrast, intermittent GH replacement therapy by s.c. injections at 12-h intervals either had no effect or suppressed serum CBG levels. In male rats, neonatal (days 1–2) gonadectomy increased CBG levels more than did prepubertal (day 25) gonadectomy, and testosterone replacement therapy reversed these effects.
It is concluded that GH increases the serum CBG levels of hypophysectomized rats when it is given in a continuous manner, but not when given intermittently. The sex difference in serum CBG levels of normal rats may, therefore, be attributed to the more continuous secretory pattern of GH previously observed in female rats.
Journal of Endocrinology (1989) 122, 725–732
Somatotrophic receptors in hepatic tissue of the developing male pig
Authors: Breier B. H. , Gluckman P. D. , Blair H. T. , McCutcheon S. N. 
Published: December 2008

ABSTRACT
The development of hepatic somatotrophic receptors and plasma concentrations of insulin-like growth factor-I (IGF-I) were investigated at five different ages (2, 20, 35, 105 and 165 days) in four male pigs per group. The specific binding of 125I-labelled porcine GH (pGH) to hepatic somatotrophic membranes was very low at 2 days of age (0·53±0·12%), and increased progressively (P <0·01) with advancing age to 3·60 ± 0·95% at 165 days of age. Specific binding of 125I-labelled bovine GH (bGH) to the same membrane preparations was markedly higher than binding of 125I-labelled pGH; it also showed a distinct developmental increase (P <0·01) with age from 4·4 ± 0·55% at 2 days of age to 24·0±1·90% at 165 days of age. Plasma concentrations of IGF-I increased significantly (P <0·01) from 79 ± 14·0 μg/l at 2 days of age to 610 ± 64·0 μg/l at 165 days of age.
Non-linear regression analysis of the competitive binding data using bGH as labelled and unlabelled ligands showed linear Scatchard plots in the three youngest age groups, with an association constant (Ka) of approximately 3·5 litres/nmol. Curvilinear Scatchard plots were observed in the two oldest age groups. The Ka for the higher affinity binding site (approximately 5·0 litres/nmol) was very similar to that for the sole site observed in the younger animals. The Ka of the lower affinity binding site was approximately 0·35 litres/nmol. There was a significant (P <0·01) developmental increase in the capacity of the higher affinity binding site from 12 ± 4·6 pmol/100 mg liver at 2 days of age to 91 ± 23·0 pmol/100 mg liver at 165 days of age.
These studies demonstrate heterogeneity of somatotrophic hepatic membranes in the pig and show that low concentrations of a high affinity binding site are already present in newborn pigs. A considerable developmental increase was observed in the capacity of this binding site which correlated significantly (r = 0·82, P <0·01, n = 20) with plasma concentrations of IGF-I. The role of the lower affinity binding site which was observed in addition to the high affinity binding site in older pigs is less clear. The data from the present study support the hypothesis that the postnatal rise in plasma concentrations of IGF-I is associated with the developmental increase of the capacity of the high affinity somatotrophic receptors.
Journal of Endocrinology (1989) 123, 25–31
Differential secretory rhythm of growth hormone controls the number of hepatic epidermal growth factor receptors in the rat
Authors: Kashimata M. , Hiramatsu M. , Minami N. 
Published: December 2008

ABSTRACT
The effect of human GH (hGH) on hepatic epidermal growth factor (EGF) receptors in the rat was investigated. Continuous administration of hGH through an osmotic minipump, mimicking the female pattern of GH secretion, to normal male rats reduced the binding of 125I-labelled EGF to hepatic membranes to the normal female levels. The same treatment of hGH applied to hypophysectomized males had no apparent effect on EGF binding. Intermittent s.c. administration of hGH twice a day (every 12 h), mimicking the male pattern of GH secretion, to hypophysectomized male and/or normal female rats, caused a significant increase in EGF binding to the levels of normal male rats. Scatchard analysis of the binding data clearly showed that the change in EGF binding was due to a change in the number of EGF receptors. The results on the affinity labelling and phosphorylation of EGF receptors were in good agreement with those showing differences in the number of EGF receptors among the experimental groups. These results indicate that the number of hepatic EGF receptors in the rat is regulated by the differential secretory rhythm of pituitary GH between the sexes.
Journal of Endocrinology (1989) 123, 75–81
Inhibitory effects of amiloride and its analogues on prostaglandin E2-stimulated fluid transport by cultured porcine thyroid cells: evidence for apical membrane Na+ channels
Authors: Matainaho T. , Cragoe E. J. , Manley S. W. , Huxham G. J. , Pearson J. V. , Bourke J. R. 
Published: December 2008

ABSTRACT
Confluent monolayers of cultured porcine thyroid cells transport fluid from the apical to the basal surface, forming circumscribed zones of detachment (domes) from the culture dish substrate. Fluid transport, as measured by increase in dome height, was stimulated by prostaglandin E2 (PGE2; 1 μmol/l) and inhibited by amiloride (0·1–100 μmol/l). Values of the inhibition constant (Ki) with 95% confidence limits for each of a series of amiloride analogues were: 3′,4′-dichlorobenzamil (DCB), 0·090 (0·045–0·18) μmol/l; 2′,4′;-dimethylbenzamil (DMB), 0·14 (0·074–0·27) μmol/l; amiloride, 0·72 (0·33–1·8) μmol/l; 5-(N,N-hexamethylene)amiloride (HMA), 17 (5·9–43) μmol/l; 5-(N-ethyl-N-isopropyl)amiloride (EIPA), 33 (15–71) μmol/l; and 2-guanidinobenzimidazole, 243 (110–570) μmol/l. Triaminopyrimidine was ineffective at concentrations up to 1 mmol/l. Since DCB and DMB are known to have a higher affinity for Na+ channels, while HMA and EIPA show higher affinity for Na+/H+ antiports, it was concluded that PGE2-stimulated fluid transport involved an apical membrane Na+ channel.
Journal of Endocrinology (1989) 123, 93–97