bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total amounts of circulating human chorionic gonadotrophin α and β subunits can be assessed throughout human pregnancy using immunoradiometric assays calibrated with the unaltered and thermally dissociated heterodimer
Authors: Nagy A-M , Glinoer D , Picelli G , Delogne-Desnoeck J , Fleury B , Courte C , Kaufman J-M , Robyn C , Meuris S 
Published: December 2008

Abstract
The aim of the present study was to determine the variations in the balance between total (free plus combined) circulating α and β subunits of human chorionic gonadotrophin (hCG) throughout human pregnancy.
The equivalence between the International Units (IU) of hCG (IRP 75/537) and those assigned to the α (IRP 75/569) and β (IRP 75/551) free subunits was experimentally determined by using intact and thermally dissociated hCG. Heat exposure (2 min at 100 °C) of hCG preparations resulted in a complete dissociation of hCG into free, soluble and intact α and β subunits. The hCG and α and β subunit contents of unaltered and heated hCG preparations were assessed by specific immunoradiometric assays. The amount of immunoreactive subunits dissociated by heat from hCG could then be evaluated on a molar basis.
Circulating hCG and its free α and β subunits were immunoassayed in 836 blood samples collected from healthy pregnant women at different gestational ages. After conversion of hCG and its subunits into a common IU system, the gestational profiles of the total amounts (free plus combined) of α- and βhCG subunits increased together and peaked at 9–10 weeks of gestation. Thereafter, total α and β subunits decreased and subsequently remained stable until term. The decline in total αhCG subunit was less marked than that of total βhCG subunit. The α- to βhCG ratio was equimolar until 10 weeks of gestation when it increased almost fourfold until term (P<0·0001). Finally, the free fraction of the total circulating αhCG subunit represented 5–7% in early pregnancy but reached 60–70% in the last trimester (P<0·0001). In contrast, the free fraction of the total βhCG subunit decreased slightly from 4–5% of total β subunit in early pregnancy to 2–3% at term (P<0·0001).
The present study suggests that thermal dissociation of hCG is a useful method with which to calibrate immunoassays on a molar basis in order to assess circulating levels of the heterodimer and its subunits.
Journal of Endocrinology (1994) 140, 513–520
The Effect of GH-Releasing Peptide-2 (GHRP-2 or KP 102) on GH Secretion from Primary Cultured Ovine Pituitary Cells Can be Abolished by a Specific GH-Releasing Factor (GRF) Receptor Antagonist
Authors: Wu Danxing , Chen Chen , Katoh Kazuo , Zhang Jin , Clarke Iain J. 
Published: December 2008

Abstract
A newly synthesised GH-releasing peptide, KP 102 (also named GHRP-2), was studied in an in vitro perifusion system of primary cultured ovine anterior pituitary cells. Application of KP 102 to the perifusion medium caused a dose-dependent increase in GH secretion. Dose-response relationships indicated that KP 102 had similar potency to GRF and was 10-fold more potent than earlier generations of GH-releasing peptide (GHRP-6 and GHRP-1) tested in same system. The response to a second application of KP 102 given within 1 h of initial application was significantly lower than the response to the first application. When KP 102 (or GRF) was applied first and then GRF (or KP 102) given 1 h later, the second response was not attenuated. When GRF and KP 102 were coadministered, an additive effect on release of GH was obtained. The effect of maximal dose of KP 102 (100nM) on GH release was totally abolished by [Ac-Tyr1, d-Arg2] GRF 1-29 (1μM) which is believed to be a specific antagonist for the GRF receptor. Blockade of Ca2+ channels by Cd2+ (2mM) diminished the basal GH secretion and abolished the increase in GH release in response to KP 102 (100nM). These data suggest that the action of KP 102 is blocked by a GRF receptor antagonist and therefore acts through a different receptor to that employed by earlier generations of GH-releasing peptides. GH release in response to KP 102 involves an increase in Ca2+ influx and there is no cross-desensitization between KP 102 and GRF responses.
Adrenocortical dysplasia: a mouse model system for adrenocortical insufficiency
Authors: Beamer W G , Sweet H O , Bronson R T , Shire J G M , Orth D N , Davisson M T 
Published: December 2008

Abstract
A spontaneous autosomal recessive mutation causing disordered morphogenesis of the adrenal cortex has been identified in DW/J inbred strain mice and named adrenocortical dysplasia (acd). The acd mutant gene has been mapped just proximal to oligosyndactyly (Os) and esterase-1 (Es-1) in the central region of chromosome 8. Both male and female acd/acd mice are characterized by reduced survival, retarded growth, skin hyperpigmentation, poorly developed pelage and focal ureteral blockage leading to hydronephrosis. Morphometric measurements showed that acd/acd cortical cells and nuclei were increased sevenfold in volume; nuclei often showed a variety of inclusions. Cortical cells of acd/acd mice contained large numbers of mitochondria, smooth endoplasmic reticulum and lipid droplets characterisitic of steroidogenic cells. While cortical X-zones failed to develop in acd/acd adrenals, medullary cells and nuclei were unaffected by mutant gene action. Resting serum corticosterone levels in female, but not male, mutant mice were significantly lower than in +/? normal littermates, whereas ACTH levels were significantly elevated in mutants of both sexes. Serum aldosterone levels were normal in acd/acd mice. Functional studies of adrenals cultured in vitro revealed that acd/acd adrenals secreted reduced amounts of corticosterone per pair of glands under both basal and ACTH-stimulated conditions. However, correction of the corticosterone secretion data to mg cortical mass in culture showed that the mutant cortical tissue secreted the same amount of glucocorticoid as did their +/? normal littermate glands. We conclude that the acd mutant gene acts in an unknown fashion to cause a fundamental defect in cellular proliferation in the adrenal cortex, leading to compensatory marked hypertrophy of cortical cells and grossly enlarged nuclei. The role of acd action in adrenal cortical development remains to be established.
Journal of Endocrinology (1994) 141, 33–43
Mechanisms of insulin-like growth factor (IGF)-II-induced IGF-I receptor down-regulation in BC3H-1 muscle cells
Authors: Rosenthal S M , Brown E J 
Published: December 2008

Abstract
Muscle is an important target tissue for insulin-like growth factor (IGF) action. We have previously demonstrated that treatment of myoblasts with IGF-II decreased IGF-I receptor biosynthesis and steady-state mRNA levels. In addition, muscle cell differentiation was associated with a marked increase in the expression and secretion of IGF-II followed by similar down-regulation of the IGF-I receptor, suggesting an autocrine role for IGF-II in this process. To explore further the mechanisms by which IGF-II decreases IGF-I receptor expression in BC3H-1 muscle cells, dose–response studies of IGF-I and -II treatment on the amount of IGF-I receptor mRNA were carried out. In addition, to determine whether IGF-II decreases IGF-I receptor expression by stimulating receptor protein degradation, pulse/chase experiments with [35S]methionine/cysteine were carried out. Both IGF-I and -II induced significant down-regulation of IGF-I receptor mRNA. At low concentrations, IGF-I was more potent than IGF-II in inhibiting IGF-I receptor mRNA accumulation, suggesting that IGF-I receptor down-regulation induced by IGF-II is mediated principally through the IGF-I receptor in these cells. In addition, IGF-II decreased IGF-I receptor expression by stimulating receptor protein degradation as demonstrated by pulse/chase analysis of metabolically labelled receptors. Thus, IGF-II induces IGF-I receptor down-regulation in muscle cells through multiple mechanisms, including decreasing IGF-I receptor mRNA and stimulating IGF-I receptor protein degradation.
Journal of Endocrinology (1994) 141, 69–74
Effects of exogenous relaxin on oxytocin and vasopressin release and the intramammary pressure response to central hyperosmotic challenge
Authors: Wilson B C , Summerlee A J S 
Published: December 2008

Abstract
Experiments were done to study the effects of porcine relaxin on osmotically evoked changes in intramammary pressure and the release of oxytocin and vasopressin in anaesthetized rats. Injections (1 μ1) of hypertonic (0·75 m) NaCl into the left lateral cerebral ventricle were used to induce consistent rises in intramammary pressure and the release of oxytocin and vasopressin. Plasma hormone concentration was determined by radioimmunoassay. Relaxin (5 μg i.v.) significantly (P<0·05) suppressed the intramammary pressure response to osmotic challenge 5 and 10 min after treatment. However, pretreatment with a specific vasopressin V1 receptor antagonist completely negated the effect of relaxin on intramammary pressure. Baseline levels of oxytocin and vasopressin in unstimulated rats were 41 ± 1·6 and 36±1·1 pmol/l respectively. Osmotic challenge induced significant (P<0·05) rises in plasma levels of both hormones (62·8 ±1·1 and 67·9 ± 1·2 pmol/l respectively) which were further augmented by relaxin (81·3±1·8 and 117·1 ±2·4 pmol/l respectively; P<0·05). The data confirm that central osmotic challenge provokes the release of oxytocin and vasopressin but the effects of oxytocin at the level of the mammary gland may be obscured by the action of vasopressin affecting blood flow to the gland.
Journalof Endocrinology (1994) 141, 75–80
Some morphological and hormonal aspects of ovulation and superovulation in the rat
Authors: Szołtys M , Galas J , Jabłonka A , Tabarowski Z 
Published: December 2008

Abstract
In the first experiment, mature female Wistar rats, displaying a regular 4-day oestrous cycle, were killed in succession every 2 or 3 h on the day of pro-oestrus and oestrus until the time of ovulation. In the second experiment, immature female Wistar rats (aged 24 days) were injected s.c. with 30 IU pregnant mare serum gonadotrophin (PMSG) and 56 h later with 20 IU human chorionic gonadotrophin (hCG). They were killed in groups at 0, 24, 48, 56 and 57 h, and then every 2 h until 72 h. Excised ovaries were homogenized and analysed for steroid content or they were submitted to a routine histological procedure. The cyclic and PMSG/hCG-treated rats exhibited some similarities and differences in the general pattern of steroid content. Either a presumptive endogenous LH surge or administration of hCG resulted in an increase in the ovarian androgen concentration which preceded a rise in progesterone; the progesterone peak, in turn, was accompanied by a fall in the amount of androgens and oestradiol. However, in comparison with cyclic rats, superovulated animals displayed a significantly higher ovarian androgen level for a prolonged period; ovarian oestradiol concentration was also raised while the progesterone content was much lower. Histological analysis revealed large differences between the ovaries of superovulated and cyclic rats, especially with regard to the maturing follicles. The majority of PMSG/hCG-derived follicles showed hypertrophied theca interna and degenerated or luteinized granulosa. A large number of preovulatory follicles did not ovulate. These results clearly indicate that PMSG/hCGinduced follicles are not equal to the follicles developing during a normal oestrous cycle. This should be taken into consideration when using superovulated animals in experiments.
Journal of Endocrinology (1994) 141, 91–100
Response of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) and IGFBP-3 to IGF-I treatment in severe insulin resistance
Authors: Quin J D , Checkley A , Gallagher A , Jones J , MacCuish A C , Miell J P 
Published: December 2008

Abstract
It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulindependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44·1 ±7·2 to 31·5 ±7·2 (s.e.m.) mmol/l (P=0·001), and insulin and C-peptide levels fell from 920 ±62 to 542±45 mU/l (P=0·008) and 5466 ±633 to 3071 ±297 pmol/l (P= 0·02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 ±10·2 to 410 ±50·1 μg/l (P=0·001), and those of IGF-II fell from 279·8± 8·3 to 104·3 ±7·9 μg/l (P=0·001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 ± 127 to 2197 ± 334 μg/l (P=0·002), despite a significant fall in GH concentrations from 10·7±2·6 to 4·1±1·1 mU/l (P= 0·007), suggesting that IGFBP-3 regulation is also IGF-I-dependent. The lack of response of IGFBP-1 to a significant fall in insulin levels suggests that impaired insulin receptor function alters the usual regulation of IGFBP-1 by insulin. These findings are of importance, given the potential use of rhIGF-I in NIDDM.
Journal of Endocrinology (1994) 141, 177–182
Transforming growth factor-β1 synthesis in human thyroid follicular cells: differential effects of iodide and plasminogen on the production of latent and active peptide forms
Authors: Cowin A J , Bidey S P 
Published: December 2008

Abstract
The present study has investigated the relative levels and interconversion of latent and active forms of transforming growth factor-β1 (TGF-β1) in human thyroid follicular cell cultures derived from sporadic non-toxic goitres. Northern blotting of RNA extracted from 72-h cultures revealed a 2·5 kb mRNA transcript hybridizing with a cDNA probe for latent TGF-β1, the intensity of which was doubled in cells exposed to Nal (10 μmol/l). Radioreceptor assay of follicular cell-conditioned medium for TGF-β1 content confirmed a similar enhancing effect of iodide. The endogenous active component of TGF-β1 present in conditioned medium represented only a minor fraction of the total TGF-β1 content, this fraction was not enhanced by exposure of follicular cells to iodide. The low level of endogenous active TGF-β1 in medium conditioned by either control or iodide-treated cells was confirmed by immunoadsorption with a precipitating antiserum against active TGF-β1, when such cells failed to show a reversal of the iodide-induced decrease in [methyl-3H]thymidine incorporation into trichloroacetic acid-precipitable material. In contrast to the inhibitory effect of iodide on de novo DNA synthesis, which appeared not to reflect an increase in active TGF-β1, the inhibitory effects of plasminogen (100 mg/l) or plasmin (2000 U/l) on [methyl-3H]thymidine incorporation into thyroid cells were reversible by TGF-β1 immunoadsorption. This provides evidence that the plasmin-mediated inhibition of DNA synthesis in thyroid follicular cells may be attributed to the growth-regulating action of an increased level of activated TGF-β1. The findings of this study therefore provide evidence that (i) human thyroid follicular cells are potentially capable of activating locally derived latent TGF-β1, (ii) an increase in thyroidal TGF-β1 mRNA and latent TGF-β1 peptide availability, following exposure of cells to iodide, is not accompanied by a corresponding increase in active TGF-β1, and (iii) within the thyroid gland, as in other epithelial tissues, activation of endogenous TGF-β1 may be dependent upon the proteolytic actions of plasmin.
Journal of Endocrinology (1994) 141, 183–190
Spermine-induced precocious intestinal maturation in suckling rats: possible involvement of glucocorticoids
Authors: Kaouass M , Sulon J , Deloyer P , Dandrifosse G 
Published: December 2008

Abstract
The mechanism(s) involved in the spermine-induced precocious postnatal maturation of the intestine in the unweaned rat was examined. Spermine given orally to 11-day-old rats stimulated ACTH and corticosterone secretion. Maximum serum levels of ACTH and corticosterone were observed between 4 and 6 h after spermine ingestion and were five- and sevenfold greater respectively than those of control rats receiving saline alone. Intraperitoneal injection of the polyamine had no effect on corticosterone production. Repeated intraperitoneal administration of gastrin, cholecystokinin, glucagon(1–37) and secretin to 11-day-old rats had no effect on the specific activity of intestinal disaccharidases.
These data indicate that (1) the hypophysial-adrenal axis is implicated in the postnatal development of the gastro-intestinal tract induced by spermine and (2) spermine affects ACTH and corticosterone secretion indirectly, probably by stimulating the release of gastrointestinal hormone(s).
Journal of Endocrinology (1994) 141, 279–283
Protein kinase C signal transduction pathway in ACTH-induced growth effect of rat adrenocortical cells in primary culture
Authors: Arola J , Heikkilä P , Voutilainen R , Kahri A I 
Published: December 2008

Abstract
ACTH exerts a biphasic effect on the growth of fetal rat adrenocortical cells in primary culture when bromodeoxyuridine (BrdU) incorporation is used as an indicator of proliferation. The immediate inhibitory effect during the first 24 h of ACTH stimulation is not dependent on cyclic AMP (cAMP). Protein kinase C (PKC) inhibitors H-7 and staurosporine blocked this inhibitory effect of ACTH, whereas 12-0-tetradecanoyl phorbol-13-acetate (TPA; a PKC activator) mimicked the ACTH-induced antimitogenic effect. The stimulatory growth effect of ACTH appears after 72 h of treatment. A similar mitogenic effect is also achieved with cAMP derivative 8-bromo cAMP (8-Br cAMP). However, both ACTH- and 8-Br cAMP-induced proliferations could be reduced with H-7.
ACTH-induced corticosterone secretion was inhibited 50% with H-7 after 24 h, but 8-Br cAMP-induced secretion was unaffected. However, if the treatments were continued for 72 h, H-7 no longer reduced the steroid secretions. Reduction (50–75%) of cholesterol side-chain cleavage enzyme (P450scc) mRNA expression was also noted with H-7 in ACTH-treated cultures after 6 and 24 h. In contrast, TPA doubled the corticosterone secretion induced by 8-Br cAMP, but did not further increase the ACTH-induced secretion after 24 h. TPA alone, however, was not able to induce steroid secretion or P450scc mRNA expression. The morphological differentiation of fetal rat adrenocortical cells with ACTH or 8-Br cAMP from zona glomerulosa-like cells into zona fasciculata-like cells was not disturbed by H-7 nor was it induced by TPA alone.
These results therefore suggest that PKC- and cAMP-dependent signal transductions are involved in the ACTH-induced biphasic growth effect of fetal rat adrenocortical cells. PKC plays a role in the inhibitory growth effect, and both PKC and cAMP are involved in the stimulatory growth phase of ACTH. Both PKC and cAMP are also involved in the steroid secretion of zona glomerulosa-type cells, but differentiation into zona fasciculata-type cells and their steroid production is transduced through cAMP.
Journal of Endocrinology (1994) 141, 285–293
Co-ordinate actions of FSH and insulin-like growth factor-I on LH receptor expression in rat granulosa cells
Authors: Kanzaki M , Hattori M-A , Horiuchi R , Kojima I 
Published: December 2008

Abstract
The actions of FSH and Insulin-like growth factor-I (IGF-I) were studied in cultured rat ovarian granulosa cells. Cells became differentiated and expressed LH receptors when they were incubated for 72 h with 200 μg FSH/l (high FSH) but not 20 μg FSH/l (low FSH). Treatment with high but not low FSH increased the release of both immunoreactive and bioactive IGF-I into the medium. A combination of low FSH and IGF-I reproduced the effect of high FSH on LH receptor expression. We then examined the critical time when low FSH and IGF-I exerted their effects. In the presence of continuous low FSH, IGF-I was capable of inducing LH receptor expression even when added 24 h after the addition of low FSH. However, when IGF-I was added at 36 h, LH receptor expression measured at 72 h was greatly reduced. In contrast to the action of IGF-I, continuous exposure to low FSH was required for LH receptor expression, and IGF-I had no effect when FSH was not included for the entire 72 h of culture.
DNA synthesis as assessed by both [3H]thymidine incorporation and nuclear bromodeoxyuridine labelling was moderate at the beginning of culture and markedly reduced at 24 h both in the presence and absence of either high FSH or low FSH plus IGF-I. In the presence of either high FSH or a combination of low FSH plus IGF-I, DNA synthesis remained decreased for up to 72 h whereas it began to increase in the absence of either high FSH or a combination of low FSH plus IGF-I. A similar increase in DNA synthesis was observed after 48 h when granulosa cells were treated with low FSH alone, which did not induce LH receptor expression. These results indicate that 1) growth and differentiation of granulosa cells are regulated inversely; 2) FSH and IGF-I act together to induce LH receptor expression; and 3) action of IGF-I is dependent on the presence of FSH.
Journal of Endocrinology (1994) 141, 301–308
Effects of a non-steroidal pure antioestrogen, ZM 189,154, on oestrogen target organs of the rat including bones
Authors: Dukes M , Chester R , Yarwood L , Wakeling A E 
Published: December 2008

Abstract
ZM 189,154 ([1RS,2RS]-2-(4-hydroxyphenyl)-2-methyl -1-[9-(4,4,5,5,5-penta-fluoropentyl)sulphinylnonyl]-1,2, 3,4-tetrahydronaphth-6-ol) is a non-steroidal pure anti-oestrogen. It has a high relative affinity for the oestrogen receptor, completely blocks the trophic action of oestradiol (OE2) on the uterus in immature and ovariectomized (OVX) adult rats and, in the latter, also completely blocks the trophic action of OE2 on vagina, bone and growth rate. ZM 189,154 displays no intrinsic oestrogen-agonist activity on uterus, vagina, bone, LH secretion or growth rate in OVX rats. Differential sensitivity of OE2-regulated processes was more apparent in intact rats. Daily doses of 0·6 mg/kg per day of ZM 189,154 blocked ovulation; 2 mg/kg per day achieved maximal uterine atrophy but did not affect bone density or growth rate; 10 mg/kg per day produced a broader spectrum of effects (reduced bone density, increased basal LH, slightly increased growth rate), but the magnitude of these was smaller than after ovariectomy; the 10 mg/kg dose also produced multiple ovarian follicular cysts. The failure of ZM 189,154 to achieve complete ovariectomy-like effects in intact rats may be due to the action of ovarian factors other than OE2, or to the circulating OE2 levels resulting from the disturbance to ovarian function posing too strong a challenge to the antagonist.
Journal of Endocrinology (1994) 141, 335–341