bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular receptors for sex steroids in human pituitary adenomas
Authors: Jaffrain-Rea M L , Petrangeli E , Ortolani F , Fraioli B , Lise A , Esposito V , Spagnoli L G , Tamburrano G , Frati L , Gulino A 
Published: December 2004

Abstract
Cellular receptors for sex steroids (SSRs) were studied in an unselected series of 55 human pituitary tumors. Cytosolic receptors for estrogen (ERcs) and progesterone (PgRcs) were determined in all cases and cytosolic androgen receptors (ARcs) in 47 cases. Nuclear receptors (ERns, PgRns, ARns) were also studied in 33 cases. ERs and PgRs were determined by an ELISA and ARs by [3H]methyltrienolone binding. Where both cytosolic and nuclear receptors were studied (n=33), ERs, PgRs and ARs were found in at least one subcellular fraction in 66·7, 60·6 and 81·8% of cases respectively, ERs and ARs being mainly recovered from the cytosol and PgRs from the nucleus. No linear correlation was found between preoperative plasma steroid hormones and their specific cellular receptors. Nonetheless, the differential expression of SSRs according to sex and gonadal status at the time of surgery strongly supports their regulation by the steroid environment in vivo: PgRcs were more frequent in tumors found in women (41·4 vs 15·4%, P<0·05), whereas a high expression of ERcs and ARcs (>15 fmol/mg protein) was more common in tumors found in men (34·5 vs 10·3%, P<0·05 and 54·5 vs 24·0% respectively). PgRs were positively correlated with ERns, indicating the possibility of estrogen priming of their expression, and negatively correlated with ARs in nuclear fractions. SSRs appeared to be widely distributed among pituitary tumors, although, compared with other hormone-secreting groups, prolactinomas displayed a higher ERc expression (34·8 ± 11·3 vs 4·8 ± 5·1 fmol/mg protein, P=0·007) and gonadotroph cell adenomas lower ARc values (1·3 ± 0·8 vs 38·2 ± 10·6 fmol/mg protein, P=0·048). Microadenomas were characterized by a higher PgR expression than macroadenomas, whereas hemorrhagic (macro)adenomas were characterized by a high ER expression (>90%). The present results indicate that most pituitary tumors are targets for sex steroids, SSR expression being partially triggered by the steroid environment itself. Possible physiopathological and therapeutic implications of these findings are discussed.
Journal of Endocrinology (1996) 151, 175–184
Inhibitory effect of dihydrotestosterone on human thyroid cell growth
Authors: Rossi R , Zatelli M C , Franceschetti P , Maestri I , Magri E , Aguiari G , Cavazzini P , degli Uberti E C , del Senno L 
Published: December 2004

Abstract
Sex steroid-binding activities have been identified by several authors in normal and pathological thyroids and the expression of the canonic androgen receptor (AR) has recently been demonstrated in human thyroid follicular cells.
In order to assess what influence, if any, androgen exposure has on thyroid cell growth, the effect of dihydrotestosterone (DHT) on [3H]thymidine (thy) incorporation and cell proliferation was investigated in thyroid follicular cells in vitro. In a primary culture of goitrous cells, DHT induced a significant reduction of [3H]thy incorporation at concentrations ranging from 10−12 to 10−8 m, with a more pronounced effect at 10−9 m. At this concentration, the inhibitory effect was evident after both 24 and 48 h of treatment and in various types of primary thyroid cell cultures. In goitrous cells, the DHT-induced decrease of [3H]thy was associated with a reduction of expression of the proliferation-associated nuclear Ki-67 antigen, a protein commonly used to assess cell growth fraction. In TPC cells, an AR-positive thyroid papillary carcinoma cell line, DHT at concentrations between 10−12 and 10−8 m significantly decreased the growth rate. DHT (10−9 m) produced an approximately 50–60% inhibition of cell proliferation and the antiandrogen cyproterone acetate was capable of reversing such effects. The DHT-induced reduction of TPC cell proliferation was associated with a significant reduction of c-myc RNA levels. Thyroperoxidase mRNA levels and thyroglobulin production were not reduced by androgen in primary cultures of goitrous cells.
In conclusion, our results indicated that androgens may have a role in this gland by reducing the proliferation, but not the function, of follicular cells.
Journal of Endocrinology (1996) 151, 185–194
Role of the neuronal histaminergic system in the regulation of somatotropic function: comparison between the neonatal and the adult rat
Authors: Grilli R , Sibilia V , Torsello A , Pagani F , Guidi M , Luoni M , Netti C , Müller E E 
Published: December 2004

Abstract
To study possible age-related differences in the role of neuronal histaminergic pathways in the control of GH secretion, the effects of α-fluoromethylhistidine (α-FMH), an irreversible inhibitor of histamine (HA) synthesis, were examined on basal and opioid-induced GH release in neonatal and adult rats. The mechanisms involved in such effects were evaluated by measuring pituitary GH mRNA levels and hypothalamic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs. Daily injection of α-FMH (20 mg/kg, s.c.) in pups of either sex, from birth until 10 days of age, caused a significant increase in baseline plasma GH and potentiated the GH response to the [Met5]-enkephalin analog FK 33–824 (1 mg/kg, s.c.) administered 3 h after the last α-FMH injection. GH and SRIF mRNA levels were significantly higher in α-FMH-treated pups than in controls, whereas no difference was observed in GHRH mRNA levels. In young adult male rats, acute administration of α-FMH (100 mg/kg, s.c., 3 h before) did not change significantly basal GH levels but potentiated FK 33–824 (0·3 mg/kg, intracarotid)-induced stimulation of GH secretion. Repeated administration of α-FMH (200 μg/rat, i.c.v., for 3 days) failed to modify basal and FK 33–824-induced GH secretion, caused a significant reduction in hypothalamic GHRH mRNA levels and left SRIF and GH mRNAs unchanged.
These findings indicate that HA exerts an inhibitory effect on GH secretion in both neonatal and adult rats. The different effects of short-term HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immaturity of the HA system in early postnatal life and to a different functional role of GH-regulatory factors during ontogeny.
Journal of Endocrinology (1996) 151, 195–201
Serial analysis of the effects of methimazole therapy on circulating B cell subsets in Graves' disease
Authors: Corrales J J , Orfao A , López A , Ciudad J , Mories M T 
Published: December 2004

Abstract
The immunosuppressive effects of antithyroid drug therapy are well recognized; however, the cellular mechanisms underlying their action remain largely unknown. In the present paper we have prospectively analyzed the in vivo effects of methimazole treatment on a large number of circulating B cell subsets, involved in the effector phase of the immune response, in a group of 18 hyperthyroid patients with Graves' disease (GD). The patients were sequentially studied before (day 0) and 7, 14, 30, 90 and 180 days after methimazole therapy. The results were compared with both a group of 19 age- and sex-matched healthy controls and a group of 20 untreated/euthyroid GD patients in long-term remission. The combination of flow cytometry and three colour immunofluorescence revealed a clear increase (P<0·001) in the numbers of circulating total B cells (CD19+) due to a significant increase (P<0·001) in the CD5+, FMC7+, CD5+/FMC7+ and CD23+ B cell subsets in hyperthyroid GD patients with respect to both healthy individuals and to GD patients in long-term remission. The absolute numbers of all these B cell subsets analyzed before treatment, although abnormal, were not statistically different from those observed during the whole period of therapy. When comparing the percentages of these B cell subsets during treatment, significant changes (P<0·001) were only observed in the proportion of CD5+, CD5+/FMC7+ and CD5 −B cells at the end of the follow-up period with respect to those found both before and during the first month of therapy. Whereas CD5+ and CD5+/FMC7+ B cells decreased (P<0·001) after 3 months of therapy, CD5 − B cells showed a significant increase (P<0·001) at the end of therapy. It is remarkable that the percentage of CD5+, CD5+/FMC7+, CD5 − and CD23+ B cell subsets were abnormal during the whole period of treatment and that they never reached normal values. These results show that, in vivo, GD patients treated with methimazole exhibited an abnormal but rather stable pattern of B cell distribution, similar to that present in hyperthyroid untreated GD patients, except for the CD5+ and CD5 − B cell populations. Our findings suggest that in vivo methimazole therapy would not directly have an important influence on circulating B cell subsets.
Journal of Endocrinology (1996) 151, 231–240
Characterization of a monoclonal antibody reacting with the free human luteinizing hormone β-subunit
Authors: Pantel J , Robert P , Troalen F , Chanson P , Schaison G , Bellet D , Bidart J-M 
Published: December 2004

Abstract
Measurement of serum luteinizing hormone (hLH) is important for the detection and follow-up of patients with pathological processes of the reproductive axis. Detection of the uncombined form of the β-subunit of hLH, or free hLHβ, has proved to be of clinical interest in the recognition of gonadotroph adenomas. As no monoclonal antibody specific for the free hLHβ is at present available, we elicited monoclonal antibodies using free hLHβ as an immunogen. An antibody, named BLH01, was selected for its specific binding to the free β-subunit, and its antibody-binding site was characterized at the molecular level, emphasizing the importance of amino acid residues located between the disulfide-bonded Cys93 and Cys100. This region has been demonstrated as being particularly critical for the specific binding of lutropic hormones to their receptors. Topographic assignment of the epitope recognized by BLH01 was then achieved by cross-matching studies based on a library of antibodies directed to hLHβ, and the location of some epitopes on the three-dimensional model of the β-subunit is proposed. A two-site immunoassay based on BLH01 as capture antibody was then developed. This assay, using BLH01, may constitute a simple, sensitive and highly specific procedure for assessing the clinical usefulness of measuring free hLHβ, particularly for the diagnosis and follow-up of patients presenting with pituitary adenomas.
Journal of Endocrinology (1996) 151, 251–258
Reduction in circulating IGF-I and hepatic IGF-I mRNA levels after caecal ligation and puncture are associated with differential regulation of hepatic IGF-binding protein-1, -2 and -3 mRNA levels
Authors: Rodríguez-Arnao J , Yarwood G , Ferguson C , Miell J , Hinds C J , Ross R J M 
Published: December 2004

Abstract
Sepsis is characterized by a severe shift in metabolism, characterized by low IGF-I levels. We have studied the influence of caecal ligation and puncture (CLP) on the levels of circulating IGF-I and hepatic IGF-I and IGF-binding protein (IGFBP)-1, -2 and -3 mRNA in adult male Wistar rats (n=12) and compared it with sham-operated rats (n=6). In order to exclude anorexia-induced changes we also studied animals pair-fed to both groups. IGF-I levels were measured by RIA. Steady-state hepatic IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 mRNA levels were measured by Northern blot analysis using specific rat cDNA probes. Food intake averaged 13·0 ± 2·0 g/day in the sham-operated rats fed ad libitum during the study period, with a sharp decline in food intake in the CLP animals (2·3 ± 1·3 g/day). After CLP, there was a significant reduction in circulating IGF-I levels (467·2 ± 50·9 μg/l) compared with sham-operated animals (924·0 ± 75·3 μg/l; P=0·04) or those pair-fed to the CLP rats (612·5 ± 52·9 μg/l; P=0·04). Total hepatic IGF-I mRNA levels were significantly reduced (2·57 ± 0·05 densitometric units (DU)) after CLP compared with the sham-operated group (2·71 ± 0·04; P=0·04), or their pair-fed controls (2·75 ± 0·08 DU; P<0·05). Hepatic IGFBP-3 mRNA levels were lower after CLP (0·37 ± 0·04 DU) than in the sham-operated animals (0·66 ± 0·09 DU; P=0·04) or their pair-fed controls (0·61 ± 0·05 DU; P=0·04). On the other hand, hepatic IGFBP-2 mRNA levels were increased after CLP (0·91 ± 0·11 DU) compared with sham-operated animals (0·28 ± 0·06 DU; P=0·01) or with their pair-fed controls (0·22 ± 0·22; P=0·01), as were hepatic IGFBP-1 mRNA levels (CLP animals 0·95 ± 0·11 DU; sham-operated 0·30 ± 0·04 DU, P=0·01; pair-fed 0·30 ± 0·02 DU, P=0·01). No significant difference between sham-operated animals and their pair-fed controls was observed in circulating IGF-I levels (888·0 ± 109·3 μg/l; P=not significant (N.S.)), hepatic mRNA levels for IGF-I (2·72 ± 0·06 DU; P=N.S), IGFBP-3 (0·71 ± 0·07 DU; P=N.S.), IGFBP-2 (0·25 ± 0·07 DU; P=N.S.) or IGFBP-1 (0·27 ± 0·06 DU; P=N.S.).
In summary, after CLP there was a reduction in both circulating and hepatic IGF-I mRNA levels associated with a specific and differential regulation of hepatic IGFBP-1, -2 and -3 mRNA levels. Although we cannot eliminate a possible effect of surgical stress combined with malnutrition, our results suggest that these changes are a specific effect of sepsis rather than simply a result of surgical stress or poor nutrition alone.
Journal of Endocrinology (1996) 151, 287–292
Retrogradely labelled neurosecretory neurones of the rat hypothalamic arcuate nucleus express Fos protein following systemic injection of GH-releasing peptide-6
Authors: Dickson S L , Doutrelant-Viltart O , Dyball R E J , Leng G 
Published: December 2004

Abstract
Previously, we demonstrated that the synthetic hexapeptide GH-releasing peptide (GHRP-6) activates a subpopulation of arcuate neurones, as reflected by increased electrical activation and by the detection of Fos protein in cell nuclei. Here we set out to determine (1) what proportion of the cells activated by GHRP-6 are neurosecretory neurones and (2) whether the cells activated by GHRP-6 contain tyrosine hydroxylase (TH; a marker of dopaminergic cells in this region) or β-endorphin. In the first study, adult male rats were injected i.v. with the retrograde tracer, Fluorogold, to detect cells which project outside the blood–brain barrier (and are therefore likely to be neurosecretory neurones). Three days later the conscious rats were injected i.v. with 50 μg GHRP-6 and the brains processed for the immunocytochemical detection of Fos protein. Between 68% and 82% of the arcuate neurones expressing Fos protein following GHRP-6 injection were retrogradely labelled with Fluorogold. In the second study, conscious male rats, bearing a chronically implanted jugular catheter, were killed 90 min following an i.v. injection of 50 μg GHRP-6 and the brains were processed for the double immunocytochemical detection of Fos protein and either TH or β-endorphin. Less than 7% (mean ± s.e.m.= 6·7 ± 2·6% nuclei/section per rat) of the arcuate neurones expressing Fos protein following GHRP-6 injection were TH-containing cells. Of 143β-endorphin-containing arcuate cells detected only four cells were identified as containing Fos protein. Thus, the majority of arcuate neurones activated by GHRP-6 (1) project outside the blood–brain barrier (and are therefore likely to be neurosecretory neurones) and (2) were not identified as TH- or β-endorphin-containing cells.
Journal of Endocrinology (1996) 151, 323–331
Insulin-like growth factor I enhancement of steroidogenesis by bovine granulosa cells and thecal cells: dependence on de novo cholesterol synthesis
Authors: Spicer L J , Hamilton T D , Keefer B E 
Published: December 2004

Abstract
Studies were conducted to determine the importance of de novo cholesterol synthesis and cholesterol side-chain cleavage enzyme in the action of IGF-I in bovine granulosa and thecal cells. Granulosa and thecal cells from bovine follicles were cultured for 2 days in 10% fetal calf serum and then treated with luteinizing hormone (100 ng/ml) and IGF-I (0 or 100 ng/ml) for an additional 2 days in serum-free medium. During the last 24 h of treatment, cells were concomitantly treated with simvastatin (0, 0·5 or 5 μg/ml) or 25-hydroxycholesterol (0 or 10 μg/ml). Simvastatin, a potent inhibitor of the key enzyme controlling de novo cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, completely inhibited (P<0·05) progesterone production by granulosa cells and progesterone and androstenedione production by thecal cells. Simvastatin also inhibited (P<0·05) granulosa cell and thecal cell proliferation. Concomitant treatment with mevalonate, an immediate product of HMG-CoA reductase, attenuated the inhibitory effect of simvastatin on progesterone and androstenedione production by thecal cells and blocked the inhibitory effect of simvastatin on cell proliferation. The addition of 25-hydroxycholesterol, a substrate for cholesterol side-chain cleavage enzyme, had no effect (P>0·10) on IGF-I-stimulated progesterone or androstenedione production by thecal cells and actually inhibited (P<0·05) IGF-I-stimulated progesterone production by granulosa cells. These results provide indirect evidence indicating that stimulation of HMG-CoA reductase is an important locus of IGF-I action in bovine granulosa and thecal cells, whereas IGF-I has little or no effect on side-chain cleavage enzyme activity in these same cell types under the culture conditions employed.
Journal of Endocrinology (1996) 151, 365–373
Occurrence of WE-14 and chromogranin A-derived peptides in tissues of the human and bovine gastro-entero-pancreatic system and in human neuroendocrine neoplasia
Authors: Gleeson C M , Curry W J , Johnston C F , Buchanan K D 
Published: December 2004

Abstract
Antisera were generated to the synthetic peptides SREWEDS and KELTAE which correspond to residues 315–321 and 332–337 of human chromogranin A (CgA) respectively. KELTAE represents the C-terminal hexapeptide of WE-14, and SREWEDS (residue 316 human CgA Lys/Arg substitution) represents the C-terminal heptapeptide of the Intervening Peptide, located between pancreastatin and WE-14. The antisera were employed to study the occurrence of WE-14 and CgA-derived peptides in human and bovine gastro-entero-pancreatic (GEP) tissues and in a range of human GEP neuroendocrine tumours. Immunocytochemical analyses of normal human and bovine tissues demonstrated that each antiserum immunostained endocrine cells throughout the GEP tract. Variable intensities of immunostaining were detected in neoplastic tissues. Quantitatively, the highest levels of SREWEDS and KELTAE immunoreactivity were detected in pancreatic extracts, with lower levels in gastrointestinal tissues. Elevated levels of each immunoreactant were detected in neoplastic tissues. Chromatographic analysis resolved several SREWEDS-related peptides and a major KELTAE-related peptide that co-eluted with synthetic human WE-14. The present study has demonstrated that CgA is processed to generate distinct peptide products in normal and neoplastic tissues of the GEP system. A single molecular species co-eluting with synthetic human WE-14 was predominant and consistently detected in all the tissues studied.
Journal of Endocrinology (1996) 151, 409–420
Cytokine modulation of inhibin secretion in cultured rat granulosa cells
Authors: Imai M , Yamoto M , Otani H , Nakano R 
Published: December 2004

Abstract
In the present study, we examined the effects of tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) on inhibin secretion by cultured rat granulosa cells using immunoblotting and two-site enzyme immunoassay for inhibin A (α-βA dimer). FSH stimulated the secretion of the inhibin α-βA dimer (32 kDa) by the cells in a dose-dependent manner. In addition to the predominant 32 kDa inhibin α-βA dimer staining, staining of minor immunoreactive bands was also enhanced by FSH. TNFα alone did not have any effect on inhibin secretion. Immunoblot analyses using an antiserum against α-subunit and an antiserum against βA-subunit revealed a dose-dependent inhibition by TNFα of FSH-stimulated secretion of inhibin by rat granulosa cells. Similarly, TNFα inhibited in a dose-dependent manner FSH-stimulated inhibin secretion when measured using a two-site enzyme immunoassay. IL-1β alone did not exert any effect on inhibin secretion but it inhibited FSH-stimulated inhibin release in a dose-dependent manner (using both immunoblotting and a two-site assay for inhibin A). The present observations suggest that TNFα and IL-1β inhibit gonadotrophin-stimulated inhibin production by cultured rat granulosa cells.
Journal of Endocrinology (1996) 151, 449–457
Stimulatory effects of taurine on insulin secretion by fetal rat islets cultured in vitro
Authors: Cherif H , Reusens B , Dahri S , Remacle C , Hoet J-J 
Published: December 2004

Abstract
Islets of rat fetuses born to mothers fed a low protein diet (LP) have a depressed insulin secretion in vitro in response to secretagogues. These fetuses have lower plasma levels of taurine than controls. The aim of this study was to analyze the effect of taurine on fetal islets insulin secretion. After 5 days of culture in serum containing standard RPMI medium, islets were cultured for 2 days in serum-free DME/F12 medium with 8·2 or 16·7 mm glucose alone or with taurine at 0·3 or 3 mm. They were then incubated for 120 min in Krebs Ringer solution with glucose alone (5·6 or 16·7 mm) or glucose (5·6 mm) added to leucine or arginine (both at 10 mm). In both concentrations of glucose, taurine increased the fractional insulin release by islets stimulated with secretagogues tested during the incubation. The effect did not seem to be mediated by changes in cAMP content. In a second set of experiments, islets cultured in RPMI medium for 7 days were incubated in the presence of Krebs Ringer solution with leucine (10 mm) or with sulfur amino acids (taurine at 10 mm, methionine or cysteine at 5 mm) for 120 min. Taurine and methionine stimulated insulin release at the same magnitude as leucine, whereas cysteine had no effect. In conclusion, taurine enhances insulin secretion by fetal islets, at least in vitro. Low taurine levels in fetuses from LP mothers might be implicated in their depressed insulin secretion.
Journal of Endocrinology (1996) 151, 501–506