bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of IGFBP-1 in normal and cirrhotic human livers
Authors: Ross R J M , Rodriguez-Arnao J , Donaghy A , Bentham J , Clark A , Holly J , Williams R , Gimson A 
Published: December 2008

Abstract
Cirrhosis of the liver, a condition characterised by hepatocyte regeneration, is also associated with elevated insulin levels and insulin resistance. In animal models hepatic regeneration is associated with increased IGFBP-1 gene expression. Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating insulin levels in man demonstrate a negative correlation with IGFBP-1 levels. To further our understanding of the regulation of IGFBP-1 in cirrhosis we have studied steady state levels of IGFBP-1 mRNA in human liver from three groups of patients: Group 1, tissue obtained at the time of harvesting donor liver for orthotopic liver transplantation (n=4); group 2, patients undergoing major liver resection with no histological evidence of chronic liver disease (n=4); and group 3, patients undergoing orthotopic transplantation for chronic liver failure (n=9). Simultaneous samples of serum were taken at the time of surgery in some patients and in these patients IGFBP-1 mRNA levels were related to circulating levels of IGFBP-1 and insulin.
IGFBP-1 mRNA was detectable in all the human liver samples with the greatest levels seen from the normal livers of group 2 patients. Insulin levels were elevated in the cirrhotic group 3 patients compared to a normal range as were IGFBP-1 levels. There was no relationship between circulating levels of IGFBP-1 and IGFBP-1 gene expression.
In conclusion, IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in cirrhotic liver despite high levels of insulin suggesting that there are factors other than insulin regulating IGFBP-1 gene expression.
Journal of Endocrinology (1994) 141, 377–382
Vasopressin-binding sites in the pig pituitary gland: competition by novel vasopressin antagonists suggests the existence of an unusual receptor subtype in the anterior lobe
Authors: Arsenijevic Y , Dubois-Dauphin M , Tribollet E , Manning M , Sawyer W H , Dreifuss J J 
Published: December 2008

Abstract
Arginine vasopressin (AVP) acts in the pituitary gland, in synergy with corticotrophin-releasing factor, to induce ACTH release in response to stressful stimuli. Pituitary AVP receptors in the rat are coupled to phospholipase C, as are the so-called V1-type AVP receptors. The present study examined [3H]AVP binding in membranes prepared from the anterior lobe of the pituitary gland of the pig. [3H]AVP, alone or in competition with analogues, bound to sites in the pig anterior lobe which are pharmacologically similar to those described previously by others in the rat pituitary gland. For comparison, the same competition studies were performed on membrane preparations from the rat liver which contain the classic V1-type AVP receptor. Pituitary and liver AVP-binding sites were dissimilar; both cyclic and linear V1 antagonists had, in general, a much lower affinity for pituitary AVP-binding sites than for those in the liver. Thus, Phaa-d-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 (Phaa=phenylacetyl) has a 2500-fold greater affinity for the latter (negative logarithm of inhibition constant (pKi)=9·64) than for the former (pKi=6·22). One linear antagonist, Pa-d-Tyr-Phe-Val-Asn-Arg-Pro-Arg-Arg-NH2 (Pa=propionyl) had about equal affinities for liver and pituitary membranes (pKi=6·39 and 6·53 respectively). Another compound, Phaa-d-Tyr-Phe-Val-Asn-Arg-Pro-Arg-Arg-NH2 had the highest affinity found to date for binding to AVP sites in the pituitary (pKi=7·43). These findings suggest some ideas for the design of more potent and/or selective AVP analogues acting in the pituitary gland.
Journal of Endocrinology (1994) 141, 383–391
Measurement of dimeric inhibin using a modified two-site immunoradiometric assay specific for oxidized (Met O) inhibin
Authors: Knight P G , Muttukrishna S 
Published: December 2008

Abstract
Several years ago we developed a novel two-site immunoradiometric assay (IRMA) for dimeric inhibin. However, relative to the purified 32 kDa bovine inhibin standard used at that time, the immunopotencies of crude inhibin-containing samples were much less than their biopotencies estimated by pituitary cell bioassay. In attempting to improve assay performance and resolve this discrepancy we recently discovered that introduction of a preassay oxidation step to the IRMA results in a dramatic increase in the immunopotencies of inhibin-containing test samples (e.g.: bovine, human, porcine follicular fluid (FF)) and of a new (purified in 1993) 32 kDa bovine inhibin standard. However, the oxidation step did not affect the immunopotency of our original standard (purified in 1987), indicating that this material had undergone spontaneous oxidation during long-term storage, thus accounting for its higher immunopotency in our original IRMA and providing an explanation for the discrepancy between immunoactivity and bioactivity referred to above.
These findings, together with other observations on the behaviour of oxidized and non-oxidized samples of inhibin, related peptide fragments and inhibin-containing samples in the IRMA and α subunit radioimmunoassay (RIA), indicate that the anti-βA 82–114 monoclonal antibody (E4) used as tracer in the IRMA binds selectively to the oxidized (Met O89,91,108) form of the peptide. This property of the antibody can be exploited to advantage by incorporating simple modifications to existing inhibin/activin immunoassays to ensure that all samples and standards are fully oxidized before antibody addition.
Dimeric inhibin levels in individual bovine FF samples (n=105) estimated by the 'oxidized' IRMA (9·66 ± 0·50 ng/μl) were highly correlated (r=0·90; P<0·001) with values derived using the original IRMA (0·75 ± 0·05 ng/μl) but were 13-fold higher. Levels of total immunoreactive (ir)-β (estimated by RIA) and αβ dimer in bovine FF were highly correlated (r=0·89; P<0·001) whereas no correlation existed between levels of total ir-α (estimated by RIA) and either total ir-β or αβ dimer. This observation indicates that availability of β rather than α subunit regulates the amount of dimeric inhibin produced by each follicle. Preliminary observations indicate that the modified IRMA can detect serum levels of dimeric inhibin in rats and women undergoing ovarian hyperstimulation with exogenous gonadotrophin but not in normal women or cattle.
Journal of Endocrinology (1994) 141, 417–425
Effects of recombinant human FSH in immature hypophysectomized male rats: evidence for Leydig cell-mediated action on spermatogenesis
Authors: Matikainen T , Toppari J , Vihko K K , Huhtaniemi I 
Published: December 2008

Abstract
The mode of FSH actions within the testis was studied in immature hypophysectomized male rats by treatment with recombinant human FSH (recFSH, Org 32489). To elucidate the involvement of Leydig cells and androgens in the maintenance of spermatogenesis in FSH-treated hypophysectomized rats further, the recFSH treatment was given both alone and after destruction of Leydig cells with ethane-1,2-dimethane sulphonate (EDS). Three days after hypophysectomy (at 31 days of age) the rats were given one i.p. injection of vehicle or EDS and, 4 days later, they were implanted with osmotic minipumps releasing either 0·9% (w/v) NaCl or 1 IU recFSH/day.
Recombinant FSH alone increased testicular weights 2·5-fold in 7 days (P<0·01). The effect of FSH was similar in EDS-pretreated rats (P<0·01). Testicular testosterone increased from 6·5 ± 1·6 to 16·9 ± 5·3 (s.e.m.) pmol/g tissue (P<0·05) and serum testosterone from 0·12 ± 0·02 to 0·22 ± 0·03 nmol/l (P<0·05) when the rats were treated with recFSH. EDS alone did not affect testicular testosterone but, when combined with recFSH, it totally abolished the stimulatory effect of FSH on testosterone. Testicular binding of 125I-labelled iodo human chorionic gonadotrophin (hCG) and 125I-labelled iodo recFSH was increased 2·5- and 2·1-fold respectively with recFSH treatment (P<0·01). EDS, either alone or with FSH, abolished specific testicular hCG binding (P<0·01), but had no effect on that of recFSH. However, FSH increased its own receptors only in animals not treated with EDS.
Histological analysis of the testes revealed that the diameters of the seminiferous tubules increased from 115 ± 6·1 to 160 ± 7·2 μm (P<0·05) with recFSH, and a comparable increase was observed when EDS treatment preceded that of recFSH (143 ± 1·5 μm, P<0·05 vs. controls). Quantification of the spermatogenic cells indicated that recFSH supported the progression of spermatogenesis, as shown by increased number of meiotic and haploid spermatogenic cells (P<0·05). In all EDS-treated animals, spermatogenesis was severely disturbed and only a few spermatids were seen.
In conclusion: (1) these results further support the suggestion that FSH has indirect stimulatory effects on Leydig cell function, (2) the completion of meiosis and spermiogenesis are supported by FSH, the effect of which is enhanced by the presence of Leydig cells, suggesting its dependence on androgens, and (3) we show for the first time that FSH is able to stimulate its own receptors only in the presence of Leydig cell-derived factors, probably androgens.
Journal of Endocrinology (1994) 141, 449–457
Cortisol inhibition of growth hormone-releasing hormone-stimulated growth hormone release from cultured sheep pituitary cells
Authors: Sartin J L , Kemppainen R J , Coleman E S , Steele B , Williams J C 
Published: December 2008

Abstract
Cortisol inhibits growth hormone (GH) release in short-term culture and is stimulatory in long-term cultures of rat and human pituitary cells. This study sought to determine the in vitro effects of cortisol on GH release and the signal transduction pathways mediating the effects of cortisol on GH release from cultured ovine somatotrophs. Pituitary cells were dispersed with collagenase and placed in culture medium for 4 days. The data indicate that cortisol inhibited growth hormone-releasing hormone (GHRH)-stimulated GH release by at least 2 h. In short-term culture GHRH-, forskolin- and dibutyryl cyclic AMP-stimulated GH release were inhibited by cortisol, suggesting an effect distal to the membrane and involving a protein kinase A (PKA)-dependent pathway. GH release initiated by KCl was inhibited by cortisol, but GH release caused by the calcium ionophore A23187 was unaffected. This suggests a possible action of cortisol on the calcium channels. The inhibition by cortisol of the calcium-dependent secretion of GH release appeared to play a smaller role in mediating cortisol inhibition of GH release than that seen with PKA. Attempts to overcome cortisol inhibition of GH release using puromycin, arachidonic acid or pertussis toxin were unsuccessful. Since cortisol inhibition of GH release does not occur via the mechanisms found in other cell types, cortisol inhibition of pituitary cell secretions appears to be cell-specific rather than utilizing a single inhibitory mechanism. The majority of cortisol actions on the somatotroph appear to act at a site distal to the production of cyclic AMP. In contrast to man and the rat, the sheep somatotroph does not appear to increase GH release when treated with cortisol for 24 h, perhaps related to the lack of effect of cortisol on somatotroph content of GH.
Journal of Endocrinology (1994) 141, 517–525
Human pituitary somatotropes express transforming growth factor-α and its receptor
Authors: Finley E L , King J S , Ramsdell J S 
Published: December 2008

Abstract
Transforming growth factor-α (TGF-α) is a growth-regulatory peptide produced by a variety of transformed and non-transformed cells. Among non-transformed cells, TGF-α has been identified in the prolactin (PRL)- and GH-secreting cells of the bovine anterior pituitary gland.
In this report, we have examined the expression of TGF-α in human anterior pituitary glands by Western analysis and immunohistochemistry. For the Western analysis, human pituitary glands were extracted in acid/ethanol, an acetic acid-soluble fraction was ether-precipitated and dialysed, and TGF-α was partially purified by C18 chromatography. TGF-α was then identified by immunostaining of Western transfers. Anterior pituitary extracts exhibited a major band(s) migrating at 19 kDa that was immunoreactive with a monoclonal antibody directed against the mature TGF-α. However, no evidence of the fully processed 6 kDa TGF-α was observed.
We next identified TGF-α by immunohistochemistry. Using both monoclonal and polyclonal antibodies, specific immunoreactivity was identified in a population of secretory cells in the anterior pituitary gland. Using antibodies specific for the COOH and NH3 terminals of the TGF-α precursor, a comparable number of TGF-α-positive cells were found to contain TGF-α precursor sequences. These results indicate that the 19 kDa form of TGF-α expressed in the human pituitary gland may exist as the transmembrane form.
We next sought to determine which cells express TGF-α in a human male pituitary gland. On frontal sections, TGF-α-immunopositive cells were evenly distributed in a manner and number indistinguishable from GH-immunopositive cells. By contrast, PRL-immunopositive cells in midfrontal sections were largely restricted to the lateral wings and extended dorsally to the neural lobe. TGF-α was positively co-localized to GH-immunopositive cells but not in PRL-immunopositive cells by immunostaining of consecutive sections. TGF-α-immunopositive cells were also immunopositive for the epidermal growth factor receptor, indicating that TGF-α has the capacity for autocrine action in the human pituitary gland.
These results indicate that TGF-α is expressed in the human anterior pituitary gland and it is not proteolytically processed into the mature 6 kDa form. In addition, immunohistochemistry of an adult male human pituitary gland indicates that TGF-α is expressed in somatotropes and has the capacity for autocrine action.
Journal of Endocrinology (1994) 141, 547–554
Effects of a new synthetic vitamin D analogue, EB1089, on the oestrogen-responsive growth of human breast cancer cells
Authors: James S Y , Mackay A G , Binderup L , Colston K W 
Published: December 2008

Abstract
The anti-proliferative effects of the novel vitamin D analogue, EB1089, were assessed in the hormone-dependent breast cancer cell line, MCF-7, in vitro. In the present study, EB1089 was shown to be at least an order of magnitude more potent at inhibiting MCF-7 cell proliferation than the native hormone, lα,25-dihydroxyvitamin D3 (1,25(OH)2D3). Treatment of MCF-7 cell cultures with combinations of oestradiol and EB1089 ranging from 5 × 10−11 m to 5 × 10−9 m revealed the ability of EB1089 to suppress the mitogenic effects of oestradiol in these cells dose-dependently, as determined by [3H]thymidine incorporation and cell counts. EB1089 also exhibited a significant time- and dose-dependent decrease in MCF-7 oestrogen receptor (ER) concentration, as assessed by ligand binding assay. A fourfold reduction of ER levels by 5 × 10−9 m EB1089 relative to control ER levels was observed, whilst 5 × 10−9 m 1,25(OH)2D3 produced a significant but less dramatic decrease in ER levels. In addition, reduction of ER protein in EB1089-treated cell cultures was also demonstrated using an oestrogen receptor enzyme immunoassay.
The interaction of EB1089 and anti-oestrogens on the oestradiol-stimulated growth of MCF-7 cells was investigated. The treatment of cell cultures with 5 × 10−10 m EB1089 in combination with the pure anti-oestrogen, ICI 182,780 (5 × 10−8 m), and in the presence of between 5 × 10−10 m and 5 × 10−9 m oestradiol, produced an augmented inhibition of MCF-7 cell proliferation compared with the actions of either compound alone.
This study demonstrates that EB1089 is a potent anti-proliferative agent of breast cancer cells in vitro, and that part of its mechanism to inhibit cell growth may involve the modulation of ER expression, such that the responsiveness of cells to the growth-stimulatory effects of oestradiol is diminished. This new vitamin D analogue has potential in the treatment of breast cancer.
Journal of Endocrinology (1994) 141, 555–563
Expression of Messenger Ribonucleic Acid Encoding Matrix Metalloproteinases and Their Tissue Inhibitors is Related to Menstruation
Authors: Hampton Anne L. , Salamonsen Lois A. 
Published: December 2008

ABSTRACT
Matrix metalloproteinases (MMP) degrade components of the extracellular matrix and the balance between enzyme production and that of their specific tissue inhibitors (TIMPs) is likely to be crucial for menstruation. The temporal expression of messenger (m) RNA for proMMP-1 (interstitial collagenase),proMMP-3(stromelysin 1), TIMP-1 and TIMP-2 has been examined by Northern analysis in 73 individually-dated endometrial tissue samples from normal women. Thirteen tissues expressed the mRNA for proMMP-3 and mRNA for proMMP-1 was detected in eleven of the same tissues. All of these tissues were from the menstrual (11) or perimenstrual (2) phases. No expression of mRNA for proMMP-1 or -3 was detected between cycle days 4 and 26. By contrast, mRNA for both TIMP-1 and TIMP-2 was detected in all tissue samples. The abundance of mRNA for TIMP-1 was significantly elevated in menstrual tissue compared with tissue from the rest of the cycle. TIMP-2 mRNA expression displayed considerable variability between individual tissues but mean abundance was also higher in menstrual tissue. Menstruation is therefore associated with a perturbation of the balance between the expression of MMPs and their tissue inhibitors which could lead to tissue degradation.
Glucocorticoids increase insulin-like growth factor-II mRNA accumulation in cultured human phaeochromocytoma cells
Authors: Liu J , Kahri A I , Heikkilä P , Blum W F , Voutilainen R 
Published: December 2008

Abstract
Human phaeochromocytomas abundantly express insulin-like growth factor-II (IGF-II), but its regulation and biological role in these neoplasms is not known at present. To clarify the regulation of IGF-II gene expression in phaeochromocytomas, we studied the effects of glucocorticoids, nerve growth factor (NGF), and protein kinase A and C regulators in primary cultures of human phaeochromocytoma cells. Cytoplasmic RNA was extracted and analysed by Northern and dot blotting with a 32P-labelled cDNA probe for IGF-II. Dexamethasone treatment (500 ng/ml) for 3 and 7 days resulted in a 260% and 515% increase in the accumulation of IGF-II mRNA respectively. The stimulatory effect of dexamethasone was time-and dose-dependent. The increases in the 6·0 and 2·2 kb species of IGF-II mRNAs were the most apparent. Cortisol (1 μg/ml) increased the amount of IGF-II mRNA by threefold compared with the control. NGF (200 ng/ml), dibutyryl cyclic AMP (1 mm) and 12-O-tetradecanoyl phorbol-13-acetate (a protein kinase C activator; 100 ng/ml) had no significant effect on IGF-II mRNA levels. These data suggest that IGF-II gene expression in human phaeochromocytomas may be regulated by microenvironmental glucocorticoids.
Journal of Endocrinology (1994) 142, 29–35
Seasonal variations in the ultrastructure and production of androgen-dependent proteins in the seminal vesicles of a Saharian rodent (Psammomys obesus)
Authors: Gernigon Th , Berger M , Lécher P 
Published: December 2008

Abstract
The effects of seasonal variations and experimental deprivation and substitution of androgen in the seminal vesicles of the Saharian rodent Psammomys obesus were investigated. Cytological studies showed that, during the breeding season, epithelial cells had large amounts of rough endoplasmic reticulum (RER) and substantial apocrine secretion. During the non-breeding season, RER cisternae were no longer expanded and apocrine secretion was rare. Castration during the breeding season was followed by regression of the RER and the disappearance of apocrine secretion. Treating castrated animals and animals in the non-breeding season with testosterone for 15 days caused reactivation. Eight major proteins with molecular weights of 120, 78, 67, 41, 37, 34, 21 and 14·4 kDa were present in homogenates during the breeding season; six (92, 41, 36, 35, 21 and 14·4 kDa) were found in seminal vesicle secretions. During the non-breeding season, the very large amounts of the 21 kDa protein were greatly reduced; conversely the 45 kDa protein increased. Electrophoretic patterns of homogenates from animals castrated during the breeding season showed eight proteins differentially induced (37, 34, 21 and 18 kDa) or repressed (67, 45, 38 and 35 kDa) by testosterone, of which the 21 kDa protein decreased most dramatically after castration. The effects of castration were reversed by the administration of testosterone. During the non-breeding season, the synthesis of the four induced proteins was stimulated by testosterone treatment; conversely that of the 45 kDa protein was suppressed.
Journal of Endocrinology (1994) 142, 37–46
Regulation of rat thyroxine-binding globulin and transthyretin: studies in thyroidectomized and hypophysectomized rats given tri-iodothyronine or/and growth hormone
Authors: Vranckx R , Rouaze-Romet M , Savu L , Mechighel P , Maya M , Nunez E A 
Published: December 2008

Abstract
We have investigated the role of the thyroid compared with the hypophysis in the regulation of the two saturable thyroid hormone carriers of rat serum, thyroxine-binding globulin (TBG) and transthyretin (TTR). We examined, at serum and hepatic mRNA level, the responses of TBG and TTR to thyroidectomy (Tx), hypophysectomy (Hx) and replacement treatments with tri-iodothyronine (T3) or/and GH, both hormones which are depleted when the thyroid or hypophysis are removed. The studies were performed on male rats at the age of 8 weeks, when the developmentally regulated TBG becomes undetectable after its transient postnatal rise, while the non-developmentally regulated TTR presents its normal, age-independent level of expression.
Tx-induced TBG re-expression was completely reversed by T3 replacement and unresponsive to GH replacement. TTR in the serum, on the other hand, was not affected by Tx or T3 replacement, moderately reduced by Tx in terms of the amount of mRNA, and markedly reduced by GH replacement. GH treatment, moreover, inhibited the expression of TTR in euthyroid controls. Hx, like Tx, induced TBG re-expression, an effect efficiently antagonized by T3 replacement. However, TBG synthesis was higher in Hx than in Tx rats and less effectively antagonized by T3 replacement. Most unexpectedly, GH induced a dramatic further increase in TBG synthesis, and the TBG synthesized in the GH-replaced Hx rats was entirely resistant to down-regulation by T3 replacement. TTR was markedly decreased at both serum and hepatic levels by Hx, unaffected by T3 and further decreased by GH replacement.
Our evidence is consistent with two distinct regulatory pathways for TBG, one under direct negative control by the thyroid hormones, without GH mediation, and the other independent of the thyroid, but involving GH, possibly for its role in the control of carbohydrate metabolism. We have shown that TTR depends little on the thyroid and is regulated by pituitary factors in a complex way, since it is inhibited by Hx but also by treatment with GH. The divergent regulatory pathways of TBG and TTR may be important in the homeostasis of thyroid hormone bioavailability.
Journal of Endocrinology (1994) 142, 77–84