bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical localization of intracellular progesterone and glucocorticoid receptors in the rabbit lung
Authors: Camacho-Arroyo I , Ruiz A , Gamboa-Domínguez A , Pérez-Palacios G , Cerbón M A 
Published: December 2008

Abstract
We have determined the presence and distribution of intracellular progesterone receptors (PRs) and glucocorticoid receptors (GRs) in the lung of adult female rabbits using immunohistochemistry. The effects of ovariectomy and administration of oestradiol benzoate (10 μg for 3 consecutive days) upon PR and GR immunoreactivity were also studied. The results demonstrated the presence of both steroid hormone receptors in the female rabbit lung. PR and GR immunoreactivity was predominantly nuclear and located in alveolar epithelial cells and various interstitial cells such as polymorphonuclear leucocytes. Tissue distribution of both receptors was similar in all cases. Oestradiol treatment induced a marked increase in the number of PR immunoreactive cells compared with intact and ovariectomized female animals. Neither ovariectomy nor oestradiol treatment modified the number of GR immunoreactive cells. The presence and localization of intracellular PRs and GRs in several lung cell types suggest that they may play an important role in mediating the effects of progesterone and glucocorticoids in various physiological processes in the rabbit lung. The data also indicated an oestrogen regulation of PRs in the rabbit lung.
Journal of Endocrinology (1994) 142, 311–316
On the origin of physiologically high ratios of urinary testosterone to epitestosterone: consequences for reliable detection of testosterone administration by male athletes
Authors: Dehennin L 
Published: December 2008

Abstract
Testosterone administration to male athletes can be safely detected in the vast majority of cases by the urinary excretion ratio of testosterone to epitestosterone glucuronides (TG/EG), which may not exceed 6. Some rare cases of physiologically high TG/EG ratios (between 6 and 12) are encountered; these may be attributed to a dysregulation of the testicular secretions of epitestosterone which is decreased, and of epitestosterone sulphate (ES) which is normal or increased. Impaired hydrolysis of circulating epitestosterone sulphate by deficiency of a specific sulphatase acting on 17α-sulphates must also be considered as a possible reason for the decreased availability of epitestosterone for hepatic glucuronidation. Urinary excretions of conjugates and metabolites of testosterone and epitestosterone (expressed in nmol/mmol creatinine) have been determined by gas chromatography-mass spectrometry associated with stable isotope dilution, in a reference population of 90 healthy male subjects and in 12 subjects with chronic TG/EG>4. Urinary excretion ratios such as TG/(EG+ES), EG/ES and TG/5-androstene-3β,17α-diol glucuronide are shown to be efficient criteria which allow discrimination between physiologically high and pharmacologically high TG/EG ratios. A simple oral loading test with deuterium-labelled epitestosterone demonstrates the difference between hepatic and total epitestosterone metabolism clearly, particularly in subjects with physiologically high TG/EG in comparison with subjects with normal TG/EG.
Journal of Endocrinology (1994) 142, 353–360
A novel hypothyroid 'growth-retarded' mouse derived from Snell's dwarf mouse
Authors: Yoshida T , Yamanaka K , Atsumi S , Tsumura H , Sasaki R , Tomita K , Ishikawa E , Ozawa H , Watanabe K , Totsuka T 
Published: December 2008

Abstract
This paper describes a novel mutant mouse that has been spontaneously derived from the Snell's dwarf (DW/J) mouse. It was named the 'growth-retarded mouse' because of a characteristic growth pause followed by the delayed onset of pubertal growth. The onset of the increase in pituitary GH content that normally occurs concomitant with pubertal growth was also delayed in the growth-retarded mice. The serum concentration of thyroxine was very low in these mice from the neonatal period through adulthood, and a supplement of tri-iodothyronine was effective in shortening the growth pause and commencing the suppressed pubertal growth. Histological and immunohistochemical studies revealed that the anterior pituitary gland of the growth-retarded mouse contains clustered unusual chromophobic cells which are not reactive to various antisera against anterior pituitary hormones and the gland becomes enlarged with age. Breeding data indicated that these characteristics of the mice show an autosomal recessive inheritance and the gene responsible was designated as 'grm'. Partial linkage analysis utilizing microsatellite polymorphism demonstrated that the grm gene does not identify with the lit or hyt genes. Based on comparison of the hormonal status and growth pattern between growth-retarded, dwarf and normal mice, we have suggested the existence of a mutual interaction, possibly positive feedback regulation, between the pituitary and thyroid glands, that develops or matures the hormonal network which is responsible for rapid somatic growth and metabolic changes at puberty in mice.
Journal of Endocrinology (1994) 142, 435–446
Placental production of human chorionic gonadotrophin α and β subunits in early pregnancy as evidenced in fluid from the exocoelomic cavity
Authors: Nagy A-M , Jauniaux E , Jurkovic D , Meuris S 
Published: December 2008

Abstract
Levels of human chorionic gonadotrophin (hCG) and of its free α and β subunits were measured using specific immunoradiometric assays in exocoelomic fluid (ECF) and maternal serum (MS) collected from five pregnant women at 6·6-8 weeks of gestation. Mean levels of hCG and its free subunits were significantly (P<0·001) higher in ECF than in MS: 3·5-fold for hCG, 600-fold for free αhCG and 38-fold for βhCG. There was no correlation between either hCG levels or levels of its free subunits in ECF and MS. On a molar basis, the quantity of free αhCG subunit expressed as a percentage of the total (free+combined) amount was 83% in ECF and 2·7% in MS (P<0·001). The amount of free βhCG subunit as a percentage of the total was 22% in ECF and 3·5% in MS (P<0·001). The ratio of the total amounts of α- and βhCG subunits amounted to 4·6 in ECF and 0·99 in MS (P<0·001).
The heterogeneity of hCG was further investigated by polyacrylamide gel electrophoresis followed by immunoblotting. Several bands with molecular mass ranging from 42 to 57 kDa, corresponding to hCG dimers, were immunodetected in ECF and MS with anti-αhCG and anti-βhCG monoclonal antibodies. A free 35 kDa βhCG immunoreactive band was found in ECF and MS. A free αhCG immunoreactive band was observed at 23 kDa in ECF and at 21 kDa in MS.
These findings suggest that the exocoelomic cavity is a reservoir where hCG and its subunits produced by trophoblast accumulate directly. The excess of a free heavy αhCG subunit in ECF supports the hypothesis that, during early pregnancy, there is an excess of αhCG over βhCG subunit secretion by the trophoblast.
Journal of Endocrinology (1994) 142, 511–516
Mechanisms of reproductive deficiency in male rats treated neonatally with a gonadotrophin-releasing hormone antagonist
Authors: Pinilla L , Garnelo P , Tena-Sempere M , Gaytan F , Aguilar E 
Published: December 2008

Abstract
It is well known that males injected neonatally with oestradiol or antiserum or antagonists (ANT) against gonadotrophin-releasing hormone (GnRH) show multiple reproductive disorders. In the present work, in males treated neonatally with GnRH-ANT, we have analysed: (1) whether the impairment of reproductive function can be blocked by simultaneous treatment with gonadotrophins, (2) the possible differences in the effects of GnRH-ANT injected before or after the proliferation of Sertoli cells which takes place between days 1 and 15 of age, and (3) the mechanism(s) for the increased FSH secretion observed in adulthood. Experimental designs included: administration of GnRH-ANT between days 1 and 16 or 15 and 30 of age, simultaneous administration of gonadotrophins and GnRH-ANT to neonatal males, and measurement of FSH secretion after orchidectomy or specific destruction of Leydig cells with ethylene dimethane sulphonate (EDS) in adult males treated neonatally with GnRH-ANT.
The principal new data presented in our studies are the following: (1) delayed puberty was observed not only in males injected neonatally with GnRH-ANT, but also in those injected with gonadotrophins or with GnRH-ANT and gonadotrophins, (2) the decreased fertility and increased FSH secretion observed in adult males treated neonatally with GnRH-ANT were normalized by simultaneous administration of GnRH-ANT and gonadotrophins, and (3) the increased FSH secretion in adult males treated neonatally with GnRH-ANT remained after EDS or orchidectomy, suggesting that mechanisms other than decreased inhibin secretion were involved in the increased secretion of FSH.
Journal of Endocrinology (1994) 142, 517–525
Differential effects of the administration of human chorionic gonadotropin to postnatal rats
Authors: Gaytan F , Pinilla L , Romero J L , Aguilar E 
Published: December 2008

Abstract
Neonatal and prepubertal male rats were treated with human chorionic gonadotropin (hCG, 5 IU/g body weight per day) on days 2–4 or 20–22. Depending on the date of treatment, different groups of rats were sacrificed at 5, 23, 30 and 100 days of age, in order to study the short-and long-term effects of the treatment with hCG on the development of the testes and sex accessory organs. Rats treated with hCG on days 2–4 showed increased number and size of foetal Leydig cells at 5 days of age. However, long-term effects include decreased numbers of adult-type Leydig cells, decreased weight of the testes and sex accessory organs, decreased basal and hCG-stimulated testosterone secretion, and delayed balano-preputial separation. In contrast, animals treated with hCG on days 20–22 showed similar short- and long-term effects, consisting of increased number of adult-type Leydig cells and macrophages, increased weight of the testes and sex accessory organs and advanced balano-preputial separation. In adulthood, both groups showed normal reproductive function.
These results seem to indicate that the effects of hCG treatment in prepubertal rats are dependent on the type of Leydig cell stimulated, and suggest that foetal Leydig cells play a regulatory role in the early postnatal testicular development.
Journal of Endocrinology (1994) 142, 527–534
Improvement of mild hypoinsulinaemic diabetes in the rat by low non-toxic doses of vanadate
Authors: Henquin J C , Carton F , Ongemba L N , Becker D J 
Published: December 2008

Abstract
To exert their anti-diabetic effects in animals with overt alterations of glucose homeostasis, vanadium salts must be administered in high doses, which also cause decreases in food intake and body weight gain. In this study, we evaluated the effect of low doses of vanadate in rats made mildly diabetic (fed plasma glucose levels ∼11 mmol/l) and moderately hypoinsulinaemic by the injection of streptozotocin 4 days after birth. Vanadate was added to food and drinking water, at concentrations that led to the consumption of about 1 mg vanadium element per day (∼2·65 mg vanadium/kg per day in adult rats), i.e. three to fivefold less than in previous studies. The treatment was started at weaning and lasted 22 weeks (V rats), or was administered for 9 weeks only from the age of 3 months (C-V rats). Food intake and body weight gain were not affected in V rats and decreased by no more than 10% in C-V rats. In V rats, fasted and fed plasma glucose levels were decreased by about 0·5 and 2–3 mmol/l, respectively. The rises in glycaemia after three oral glucose tolerance tests were also clearly attenuated. These effects were not accompanied by any changes in plasma insulin levels. Pancreatic insulin reserves (decreased by two-thirds as compared with normal rats) were not affected by the treatment. A decrease in plasma glucose levels was also noted in C-V rats, and this improvement disappeared upon cessation of the treatment. In conclusion, oral vanadate improves glucose homeostasis in rats with moderate insulin deficiency and diabetes, even when the element is administered at low doses which have practically no repercussions on food intake and body weight gain. This indicates that vanadium salts have genuine beneficial effects on glucose metabolism in vivo.
Journal of Endocrinology (1994) 142, 555–561
Insulin-like growth factors-I and -II and their binding proteins during postnatal development of dwarf Snell mice before and during growth hormone and thyroxine therapy
Authors: van Buul-Offers S C , Bloemen R J , Reijnen-Gresnigt M G , van Leiden H A , Hoogerbrugge C M , Van den Brande J L 
Published: December 2008

Abstract
The ontogeny of serum insulin-like growth factors (IGFs)-I and -II and their binding proteins (IGFBPs) was studied in normal and dwarf Snell mice. IGF-I concentrations in serum of normal mice increased between 4 and 8 weeks of age; dwarf mice had very low serum IGF-I levels. In both normals and dwarfs, serum IGF-II levels were highest soon after birth and dropped steadily thereafter. Western ligand blots of serum IGFBPs with 125I-IGF-II as tracer revealed the expected bands 41·5, 38·5, 30–32 and 24 kDa. In normal mice the IGFBP-3 doublet was already detectable at 2 weeks of age, and its intensity increased with age. In dwarf mice the IGFBP-3 doublet was hardly detectable.
The changes of IGFs and their IGFBPs were studied in sera of dwarf mice after treatment with growth hormone (GH) and/or thyroxine (T4) for 4 weeks. In spite of a comparable growth response obtained using these hormones, serum IGF-I was increased only by GH treatment; a small but significant decrease of serum IGF-II was obtained following GH or T4 treatment. An increase of the IGFBP-3 doublet was only obtained with GH; T4 and GH+T4 had no effect. The rise of IGFBP-3 after GH treatment was accompanied by the formation of the IGFBP 150 kDa complex, as measured by neutral gel chromatography. The size distribution of 125 I-IGF-II was restored to normal, while with 125I-IGF-I only a small peak at 150 kDa was observed. Elution profiles of sera after treatment with T4 or GH+T4 were identical to those of dwarf controls.
The presence of the IGFBPs was investigated in media conditioned by liver and lung explants of normal and dwarf animals. In culture media of liver explants from normal mice, bands at 30–32 and 24 kDa predominated; the intensity of the IGFBP-3 doublet was relatively low. In dwarfs the 30–32 kDa predominated. In culture media of the lung from normal mice the IGFBP-3 doublet and the 24 kDa band were clearly visible; in dwarf mice IGFBPs could not be detected. We were unable to identify the 150 kDa IGFBP-complex in this medium using the size distribution of 125I-IGFs on neutral gel chromatography after incubation with the conditioned media. This was in contrast to data obtained with normal serum.
Our data suggest that serum IGFBP-3 and IGF-I are regulated by GH and not by T4. In dwarf Snell mice, serum IGF-II is down regulated by GH as well as T4. The 150 kDa IGFBP complex is absent in dwarfs and, when induced by GH, seems to have a high affinity for IGF-II.
Journal of Endocrinology (1994) 143, 191–198
Genistein but not staurosporine can inhibit the mitogenic signal evoked by lithium in rat thyroid cells (FRTL-5)
Authors: Takano T , Takada K , Tada H , Nishiyama S , Amino N 
Published: December 2008

Abstract
Long-term administration of lithium is one of the well-known causes of goiter. It can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid-stimulating hormone (TSH). To investigate the mitogenic signal transduction system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were studied using two protein kinase inhibitors, genistein as a specific tyrosine kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C.
Genistein but not staurosporine blocked the DNA synthesis induced by lithium in TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175 kDa substrate in the presence of lithium but staurosporine failed to do so. Moreover, lithium could also stimulate DNA synthesis in protein kinase C down-regulated cells.
These data demonstrate that lithium may require the activation of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce cell proliferation. It is suggested that the phorbol ester-sensitive protein kinase C family might not participate in the mitogenic signal transduction pathway activated by lithium.
Journal of Endocrinology (1994) 143, 221–226
Studies on the use of cultured cells in a bioassay for parathyroid hormone
Authors: Armston A E , Wood P J 
Published: December 2008

Abstract
Measurement of parathyroid hormone (PTH) is important for diagnosing hyper- and hypoparathyroidism. The move to two-site immunometric assays that detect the whole molecule has improved the discrimination of these conditions but these assays may be too restrictive because some PTH fragments that are biologically active may not be detected. In addition, PTH-like peptide of malignancy, an important cause of malignancy-associated hypercalcaemia, is not detected by the two-site assays.
Experiments were performed to set up a simple, robust and inexpensive bioassay for PTH, exploiting a kidney cell line and using cyclic AMP or an eluted stain assay as the end point. Of the 12 cell lines tested, an opossum kidney (WOK) cell line showed the most promise. Despite optimization of the procedure to include pre-treatment with dexamethasone, insulin and PTH, followed by incubation in the presence of 5′ -guanylimidodiphosphate, isobutyl-1-methylxanthine and forskolin, the WOK cells showed insufficient sensitivity for use in a cultured cell bioassay for PTH in human serum. In addition, the cells were less sensitive to PTH-like peptide precluding their use for an assay for this molecule.
Journal of Endocrinology (1994) 143, 261–268
Involvement of epidermal growth factor (EGF)/EGF receptor autocrine and paracrine mechanism in human trophoblast cells: functional differentiation in vitro
Authors: Amemiya K , Kurachi H , Adachi H , Morishige K-I , Adachi K , Imai T , Miyake A 
Published: December 2008

Abstract
We have studied the expression of epidermal growth factor (EGF) and EGF receptors (EGF-R) in isolated human trophoblast cells at various stages of differentiation and also the biological significance of the EGF/EGF-R autocrine and paracrine mechanism. Cytotrophoblast cells were isolated from human placental tissues of 6–9 weeks of gestation. Trophoblast cells underwent morphological and functional differentiation during in vitro culture. The expression of EGF and EGF-R protein and mRNA was studied in trophoblast cells cultured for 0–5 days, using immunocytochemical staining, and reverse transcription and polymerase chain reaction. Monoclonal antibodies (mAbs) against EGF and EGF-R showed specific staining in trophoblast cells at all stages of differentiation. Both EGF and EGF-R gene transcripts were detected in RNA samples isolated from trophoblast cells at all stages. These data suggest the presence of an EGF/EGF-R autocrine and paracrine mechanism in human trophoblast cells. Next, we examined the biological significance of this mechanism on trophoblast cell differentiation in vitro. EGF added to the culture medium significantly increased human chorionic gonadotrophin-β (hCG-β) secretion and, more importantly, anti-EGF neutralizing mAbs significantly reduced both hCG-β and human placental lactogen secretion from trophoblast cells in culture. All these results suggest that human trophoblast cells express both EGF and EGF-R, and that EGF may play an important role in the functional differentiation of human trophoblast cells.
Journal of Endocrinology (1994) 143, 291–301
Endothelin-1 is involved in the transient hypoparathyroidism seen in patients undergoing thyroid surgery
Authors: Nomura K , Yamashita J , Ogawa M 
Published: December 2008

Abstract
We have studied the serial changes in plasma endothelin (ET)-1, serum parathyroid hormone (PTH) and serum calcium concentrations during surgery in 20 patients undergoing a hemithyroidectomy for thyroid carcinoma. The plasma ET-1 concentrations increased within the first 24 h following surgery in 18 out of 20 cases with the peak concentration achieved between 1 and 12 h. Gel permeation chromatography showed only one major peak at the elution position of human ET-1 standard both in the pre- and postoperative plasma. Thirteen patients showed transient hypoPTHaemia and hypocalcaemia which clearly coincided with the peak plasma ET-1 concentration in 12. However, there was no significant association between the extent of the increase in the plasma ET-1 levels and the incidence of the transient hypoparathyroidism. When blood was sampled at multiple sites during surgery, the plasma ET-1 concentrations tended to be higher in the internal jugular vein on the side of the preserved thyroid lobe (4·92 ±2·21 pg/ml) as well as on the side of the lobectomy (4·36 ±1·95 compared with that in the antecubital vein (3·66± 1·44). Furthermore, tissue extracts from the parathyroid and thyroid contained considerably greater amounts of immunoreactive (ir-) ET-1 than most of the other tissues tested. In vivo experiments in animals revealed that a continuous infusion of ET-1 directly into the arterial bed supplying the preserved parathyroid glands can lead to a fall in serum PTH and Ca concentrations, whereas a bolus infusion into the artery or even a continuous infusion into the peripheral vein failed to do so, suggesting that the local increase in ET-1 may provoke this effect. All these results indicate that the transient increase in the plasma ET-1 level may be responsible for the transient hypoparathyroidism seen in patients after thyroid surgery despite successful preservation of the parathyroid glands. This effect may be mediated either through its vasoconstrictive activity or by its inhibitory effect on PTH secretion.
Journal of Endocrinology (1994) 143, 343–351