bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulation of inhibin during the luteal-follicular phase transition of the primate menstrual cycle fails to affect FSH secretion
Authors: Fraser H M , Tsonis C G 
Published: December 2008

Abstract
The pattern of inhibin concentrations in blood during the menstrual cycle in primates has suggested an endocrine role of inhibin in the negative feedback control of FSH secretion during the luteal phase. Conversely, the fall in inhibin during the late luteal phase may play a role in the rise in serum FSH during the luteal-follicular phase transition. This hypothesis was examined by determining the effects of manipulation of inhibin on FSH secretion in stumptailed macaques. During the mid-luteal phase the putative inhibin feedback was inhibited by i.v. administration of 20 ml of ovine antiserum to human recombinant inhibin in 4 macaques. FSH secretion was unaffected during the initial 24 h period post-treatment and the timing of the rise in FSH which occurred during the subsequent luteal-follicular phase transition was normal. To determine whether the elevated serum concentrations of FSH observed during the early follicular phase could be reduced by administration of inhibin, 5 cyclic macaques were treated with 200 μg of recombinant human inhibin i.v. Serum FSH concentrations were unaltered. These results suggest that inhibin does not play a major role in modulating FSH secretion during the luteal-follicular phase transition.
Journal of Endocrinology (1994) 142, 181–186
Pharmacological characterization of the nucleotide receptors that mobilize Ca2+ ions in human parathyroid cells
Authors: Gibb C A , Cook D I , Delbridge L , Conigrave A D 
Published: December 2008

Abstract
We have used the fluorescent probe fura-2 to perform agonist studies of the receptor(s) that mobilizes Ca2+ ions in response to extracellular ATP in human parathyroid cells. Extracellular ATP induced Ca2+ responses in both normal and adenomatous parathyroid cells. Activation resulted in an initial small transient response during which Ca2+ ions were released from intracellular stores, followed by a prominent plateau response during which Ca2+ ions entered the cells from the extracellular fluid. The responses exhibited moderate desensitization upon repeated stimulation with ATP, and the ratio of the plateau to the peak response remained constant for any given group of activated cells. The baseline intracellular calcium concentration was 100 ± 4·3 nm (mean ± s.e.m., n=3). Following maximal activation by extracellular ATP it rose to a peak of 684 ± 45·7 nm (n=3) and a plateau level of 415 ± 9·9 nm (n=3).
We examined the effects of a variety of nucleotide species. The order of potency was: adenosine, AMP<α,β-methylene ATP<ADP<ATP≈UTP. In the concentration range 1–1000 μm, UTP (the concentration of agonist inducing a half-maximal response, EC50=2·4 μm) was slightly more potent than ATP EC50=3·6 μm), and the two nucleotides evoked similar maximal responses. In the concentration range 0·01–1·0 μm, however, there was a clear difference in the behaviour of the two nucleotides. In particular, ATP, but not UTP, evoked responses that suggested the presence of a second receptor of higher potency but markedly lower efficacy. Responses to 2-methylthioATP (2-MeSATP) in the concentration range 0·01–100 μm defined a dose–response curve that matched the lower concentration component of the ATP dose–response curve.
Together, these data suggest that two receptor species are involved in the Ca2+ responses. One is a nucleotide/P2U receptor that responds to ATP and UTP, which are approximately equipotent agonists; 2-MeSATP is only a weak agonist with respect to this receptor. The other belongs to the P2Y receptor subclass. It responds to 2-MeSATP, a selective agonist at P2Y receptors, and to ATP, but not to the pyrimidine nucleotide UTP.
Journal of Endocrinology (1994) 142, 277–283
Pancreatic hormones differentially regulate insulin-like growth factor (IGF)-I and IGF-binding protein production by primary rat hepatocytes
Authors: Denver R J , Nicoll C S 
Published: December 2008

Abstract
We investigated the influence of and interactions among pancreatic hormones on the secretion of insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IG-FBPs) by treating primary hepatocytes from young male Long–Evans rats with insulin or glucagon in combination with rat GH (rGH). The concentration of IGF-I secreted into the medium was estimated by radioimmunoassay after formic acid-acetone cryoextraction, and secreted IGFBPs were analysed by Western ligand blot and immunoblot; accumulation of IGF-I mRNA was analysed by Northern blot. Both insulin (0·1–100 nmol/l) and rGH (0·5, 5 and 50 pmol/l) produced a dose-dependent stimulation of IGF-I secretion over a 24-h incubation period. In contrast, glucagon (0·1–100 nmol/l) inhibited IGF-I production in a dose-related manner. Glucagon (10 nmol/l) also inhibited IGF-I secretion stimulated by rGH (5 pmol/l) and insulin (10 nmol/l). Northern blot analysis of total RNA isolated from rat hepatocytes revealed that rGH (5 pmol/l) elevated IGF-I mRNA levels, glucagon (10 nmol/l) alone had no effect on this parameter, but glucagon significantly reduced IGF-I transcript accumulation in response to rGH. IGFBPs secreted by rat hepatocytes run in two molecular weight ranges on SDS-PAGE: ∼ 25 kDa (IGFBP-4) and ∼29–31 kDa (IGFBP-1 and -2); the predominant hormonally regulated IGFBP was identified as IGFBP-1. Insulin produced a dose-dependent inhibition of production of IGFBP-1, while glucagon was stimulatory; when given together at an equivalent concentration (1 nmol/l), the effects of insulin were dominant to glucagon on IGFBP-1. These observations provide support for significant opposite roles for the pancreatic hormones, insulin and glucagon, in the regulation of liver IGF-I and IGFBP-1 production. As the production of pancreatic hormones is influenced by nutritional status, these polypeptides may mediate the effects of changing nutritional state on the hormonal control of protein anabolism and glucose homeostasis by directly influencing the circulating level of liver-derived IGF-I and its binding proteins.
Journal of Endocrinology (1994) 142, 299–310
Increase of basic fibroblast growth factor (FGF) and FGF receptor messenger RNA during rat thyroid hyperplasia: temporal changes and cellular distribution
Authors: Becks G P , Logan A , Phillips I D , Wang J-F , Smith C , DeSousa D , Hill D J 
Published: December 2008

Abstract
Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. Involution of thyroid growth was then observed at 16 weeks, 4 weeks after withdrawal of goitrogens and reversion to a normal diet. Experimental animals quickly became hypothyroid compared with controls and exhibited thyroid hyperplasia (control (n=10): total serum thyroxine (T4) 66 ±4 nmol/l, thyroid weight 5 ± 1 mg/100 g body weight, means± s.d.; experimental (n=10): T4 undetectable, thyroid weight 27 ±4 mg/100 g body weight after 2 weeks of treatment). Thyroid growth rate subsequently slowed between 2 and 10 weeks. Messenger RNA for basic fibroblast growth factor (basic FGF) and for the high-affinity FGF receptor, was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for basic FGF and its receptor were detectable in thyroids from control rats at all times, while none was detected in the livers from any animal. Basic FGF and receptor mRNAs increased, and were detected at greatest abundance in hyperplastic thyroids at 1 and 2 weeks respectively, during goitre formation, but subsequently declined in parallel with thyroid growth rate at 4 and 10 weeks. When quantified by radioimmunoassay, basic FGF extracted from thyroids was fivefold greater than in controls after 1 week of goitrogen treatment (control (n=4): 24±9 pmol/μg DNA; goitre (n=4): 100± 16 pmol/μg DNA; P<0·05). Basic FGF and FGF receptor mRNAs localized by in situ hybridization predominantly to the epithelial cell population within follicles. Localization by immunohistochemistry demonstrated that basic FGF was present in the thyroids of control rats, and was largely associated with the basement membrane of follicles. During thyroid hyperplasia, increased basic FGF immunoreactivity appeared over the cytoplasm of follicular epithelial cells and was lost from the extracellular matrix. Thyroid involution following removal of goitrogen/low iodine treatment was associated with a decrease in mRNA for basic FGF or its receptor, and a loss of immunoreactive basic FGF from the cytoplasm of follicular cells. These results suggest that autocrine expression of basic FGF and FGF receptor could contribute to thyroid hyperplasia in rats.
Journal of Endocrinology (1994) 142, 325–338
Insulin-releasing pituitary cells as a model for somatic cell gene therapy in diabetes mellitus
Authors: Stewart C , Taylor N A , Green I C , Docherty K , Bailey C J 
Published: December 2008

Abstract
Insulin delivery by somatic cell gene therapy was evaluated using murine pituitary AtT20MtIns-1.4 cells. These cells have been stably transfected to release human insulin by the introduction of a recombinant plasmid bearing a human preproinsulin cDNA under the control of a zinc-sensitive metallothionein promoter. 6 × 107 AtT20MtIns-1.4 cells were implanted subcutaneously into streptozotocin-diabetic mice immunosuppressed with cyclosporin A. Release of human insulin was assessed using a specific plasma human C-peptide assay. On days 1 and 2 after implantation human C-peptide concentrations were about 0·02 pmol/ml. Consumption of zinc sulphate solution (500 mg/l) as drinking fluid for days 3–5 increased plasma human C-peptide concentrations to 0·11 ±0·01 pmol/ml (mean±s.e.m.), n=11, P<0·01, and concentrations declined when zinc was discontinued. The extent of hyperglycaemia was slightly lower (P<0·05) than in a group implanted with non-transfected AtT20 cells. The study was terminated after 9 days, and tumour-like aggregations of implanted cells were identified at autopsy. These comprised a large necrotic core with insulin-containing cells at the periphery. The study provides support for the view that somatic cell gene therapy offers a potential approach to insulin delivery in diabetes mellitus.
Journal of Endocrinology (1994) 142, 339–343
Is ovarian relaxin a stimulus to placental protein 14 secretion in pregnancy?
Authors: Critchley H O D , Healy D L , Chard T 
Published: December 2008

Abstract
The objective of this study was to investigate whether relaxin might be involved in placental protein 14 (PP14) secretion by measuring serum levels of PP14 during labour and post partum in normal women with a term pregnancy given vaginal human recombinant relaxin (rhRlx) gel for induction of labour. A randomized double-blind controlled trial was conducted on 11 women with a singleton pregnancy at term admitted for induction of labour. Comparison of serum PP14 and relaxin concentrations in the control and treated groups of subjects revealed that there was an increase in serum relaxin concentrations in women receiving 3 mg or 6 mg relaxin. There was no difference in serum PP14 levels between the control and treatment groups. These findings do not support the hypothesis that relaxin is involved in the control of PP14 secretion. However, the failure of any response might be a consequence of the very small increase in systemic levels of relaxin produced by topical vaginal administration of rhRlx. Furthermore, these measurements were made in late pregnancy and hence may not relate to the events in early pregnancy, when serum levels of PP14 are maximal.
Journal of Endocrinology (1994) 142, 375–378
Prepartum adrenocortical maturation in the fetal foal: responses to ACTH1–24
Authors: Silver M , Fowden A L 
Published: December 2008

Abstract
The present study was carried out on 19 chronically catheterized mares and fetuses in late gestation (term >320 days). In six animals which were monitored up to the time of delivery of a live foal, plasma and amniotic fluid cortisol concentrations remained low until 4–5 days before parturition when there was a rapid, significant rise (P<0·05) which was not accompanied by any corresponding changes in maternal plasma cortisol. Circulating fetal ACTH concentrations became more variable close to delivery and ANOVA revealed no significant increases during this critical period, although a negative correlation between plasma ACTH and time to delivery was observed (P<0·05).
Tests on fetal adrenal responsiveness to exogenous ACTH1–24 were carried out on ten animals. Before 295 days of gestation no significant increases in fetal plasma cortisol above its basal level of 20–30 nmol/l could be elicited by ACTH, administered as a single i.v. injection (1–2 μg/kg). By 304 ± 3 days (mean ± s.e.m.) small but significant (P<0·05) increments in plasma cortisol were detected after ACTH, while in the oldest group (313 ±2 days) significant (P<0·01) 50–60% increments were seen throughout the test period (2 h). Only one fetus was tested within 3 days of delivery and here a fourfold rise in plasma cortisol was evoked by ACTH.
When changes in endogenous levels of circulating ACTH and cortisol were monitored every 15 min over 1·5- to 2-h periods in late gestation, rises in ACTH were only accompanied by concomitant increases in plasma cortisol in fetuses within 5 days of delivery (correlation coefficient r=0·58, P<0·01). Before this time, plasma cortisol concentrations remained at basal levels irrespective of any fluctuations in plasma ACTH. These findings indicate that the adrenal cortex of the fetal foal is relatively quiescent and insensitive to ACTH for most of the latter part of gestation, but that a short rapid escalation in circulating cortisol precedes its delivery.
Journal of Endocrinology (1994) 142, 417–425
Dysfunctional growth hormone receptor in a strain of sex-linked dwarf chicken: evidence for a mutation in the intracellular domain
Authors: Agarwal S K , Cogburn L A , Burnside J 
Published: December 2008

Abstract
The sex-linked dwarf (dwdw) chicken represents a valuable animal model for studying GH insensitivity and the consequence of mutations in the GH receptor (GHR) gene. We have recently reported undetectable hepatic GH-binding activity and an aberrantly sized transcript in a strain of dwdw chickens obtained from Arbor Acre Farms, Inc. (Glastonbury, CT, USA). Southern blot analysis of the chicken GHR (cGHR) gene revealed a restriction-fragment length polymorphism in HindIII and EcoRI digests of genomic DNA in this strain of dwdw chicken. In order to localize the molecular mutation, we analysed the gene structure and determined the complete sequence of the 3' untranslated region (3' UTR) of the normal cGHR. With the use of this information, we located a large deletion in the 3' end of the cGHR gene of the Connecticut (CT) strain of dwdw chicken. This deletion (1773 bp) contained 27 highly conserved amino acids of the 3' end of the coding region, the in-frame stop codon, a less frequently used poly(A) signal that is normally found 445 bp downstream of the stop codon, and a large portion of the 3' UTR. Because of this deletion, 27 novel amino acids were substituted and the open reading frame was extended for an additional 26 amino acids before reaching the transcriptional termination site. The predicted amino acid sequence of the novel carboxyl-terminus of the dwdw cGHR is largely hydrophobic with a polylysine tail, whereas the carboxyl-terminus of the wild-type (DwDw) cGHR is composed of hydrophilic amino acids. Western blot analysis using antisera directed against the extracellular domain of the cGHR confirmed that the mutant transcript was translated. These observations suggested that the mutation in the intracellular domain results in expression of a dysfunctional cGHR which could account for the phenotype of the CT dwdw chicken.
Journal of Endocrinology (1994) 142, 427–434
Interaction of endothelin-1 with porcine thyroid cells in culture: a possible autocrine factor regulating iodine metabolism
Authors: Tsushima T , Arai M , Isozaki O , Nozoe Y , Shizume K , Murakami H , Emoto N , Miyakawa M , Demura H 
Published: December 2008

Abstract
Although endothelins were originally discovered as peptides with vasoconstrictor activity, recent studies have indicated a number of endothelin (ET)-induced hormonal functions in various tissues. We have studied the interaction of endothelins with porcine thyroid cells in culture. Specific binding of 125I-labelled ET-1 was demonstrated in porcine thyroid cells. The binding was displaced equally by unlabelled ET-1 and ET-2, but receptor affinity for ET-3 was lower than that for ET-1 and -2. Scatchard analysis of the data revealed a single class of high-affinity ET-1 receptors with a Kd of 0·45 nmol/l and a binding capacity of 2100 sites/cell. SDS-PAGE and autoradiography of 125I-labelled ET-1 cross-linked with thyroid cell membranes demonstrated ET-1 binding sites with an apparent molecular weight of 50 kDa. These results indicated that ET-1 receptors in thyroid cells are type A ET receptors. In association with the presence of ET-1 receptors, porcine thyroid cells responded to ET-1 and ET-2 with an increase in c-fos mRNA expression. Although ET-1 did not affect DNA synthesis stimulated by either EGF or IGF-I, it dose-dependently inhibited TSH-induced iodide uptake and also inhibited iodide uptake stimulated by forskolin and 8-bromo-cAMP. ET-1 had no effect on TSH-stimulated cAMP production. Thus, ET-1 inhibited TSH-induced iodine metabolism by acting at the steps distal to cAMP production. In agreement with a recent report, immunoreactive ET-1 was detected in medium conditioned by porcine thyroid cells. Antibody to ET-1 was found to increase TSH-induced iodide uptake. These results are compatible with the notion that ET-1 negatively regulates TSH-induced iodide uptake in an autocrine manner.
Journal of Endocrinology (1994) 142, 463–470
Effect of blocking oestrogen synthesis with a new generation aromatase inhibitor CGS 16949A on follicular maturation induced by pregnant mare serum gonadotrophin in the immature rat
Authors: Selvaraj N , Shetty G , Vijayalakshmi K , Bhatnagar A S , Moudgal N R 
Published: December 2008

Abstract
While the endocrine role of oestrogen is well established, its function in follicular maturation as an autocrine or paracrine regulator is less well understood. This study was designed to delineate the requirement of oestrogen for follicular development in immature rats. Exogenous gonadotrophin (25 IU pregnant mare serum gonadotrophin (PMSG) per rat) was administered to 21- to 23-day old female rats to induce follicular growth and development. In the experimental animals, synthesis of oestrogen was blocked by implanting an Alzet pump containing the aromatase inhibitor (AI) CGS 16949A (fadrozole hydrochloride; 50 μg/rat per day). The treatment resulted in blockade of the PMSG induced increase in both serum and intrafollicular oestrogen (>95%), thus leading to an inhibition in uterine weight increment. Compared with the controls, ovarian weight increased markedly in both the PMSG (295%)- and PMSG+AI (216%)-primed animals.
There was no significant difference in either the proliferative capabilities of the ovarian granulosa cells or their responsiveness to human chorionic gonadotrophin (hCG; 200 pg/ml) and ovine FSH (20 ng/ml) between the PMSG- and PMSG+AI-treated groups. Histological examination of the ovary, however, indicated a decrease in the number of healthy antral follicles in the AI-treated group compared with the PMSG-primed animals but both the groups showed a percentage increase over the controls (PMSG, 225; PMSG+AI, 158). The responsiveness of the animals to an ovulatory dose of hCG was drastically reduced (>80% inhibition of ovulation) in the oestrogen-deprived animals; this could be overriden by exogenous administration of oestrogen. In conclusion, although blocking oestrogen synthesis in the PMSG-primed rat does not seem to alter the functional properties of the isolated granulosa cells in vitro there appears to be an effect on the number of follicles which complete maturation and are able to ovulate in vivo.
Journal of Endocrinology (1994) 142, 563–570
Circulating gonadotrophin surge-attenuating factor from superovulated women suppresses in vitro gonadotrophin-releasing hormone self-priming
Authors: Fowler P A , Cunningham P , Fraser M , MacGregor F , Byrne B , Pappas A , Messinis I E , Templeton A 
Published: December 2008

Abstract
A penfusion system based on ovine pituitary tissue explants was used to investigate the effects of follicular fluid (hFF) and serum from superovulated women on pituitary responsiveness to gonadotrophin-releasing hormone (GnRH). The specific aims of the study were to determine both if gonadotrophin surge-attenuating factor (GnSAF) bioactivity is present in the peripheral circulation as well as in the follicles of superovulated women and if GnSAF suppresses GnRH self-priming in vitro. Two pulses of GnRH, 1 h apart, produced marked peaks in LH secreted from control chambers, with GnRH self-priming evident in the significant difference between the first (134·4±1·7–232·1±24·0% of basal secretion) and second (183·9±15·8–313·9±14·0% of basal secretion) LH peaks. Both follicular fluid and serum pooled from two different groups of women produced marked suppression of the first (unprimed) and second (primed) LH peaks. The hFF reduced the first LH peak to 69·6±7·8 and 60·2±9·7% and the second LH peak to 57·4±6·7 and 42·6±6·5% of control LH secretion. Overall, the serum reduced the first and second LH peaks to 76·8±4·2 and 62·9±3·6% of control respectively. These results demonstrated that GnSAF bioactivity suppresses GnRH self-priming, and is present in both the peripheral circulation and hFF. The same material administered to dispersed ovine pituitary monolayers produced similar marked suppression of GnRH-induced LH secretion, with approximately 50-fold less GnSAF bioactivity in serum compared with hFF. Combined doses of oestradiol and progesterone, or hFF from large follicles containing little GnSAF, produced stimulation of GnRH-induced LH secretion and GnRH self-priming (second peaks 78·1±38·9 and 27·4±15·7% respectively higher than first peaks). Thus, in conclusion, GnSAF in hFF and serum markedly attenuated both unprimed and primed pituitary response to GnRH, virtually abolishing the GnRH self-priming effect.
Journal of Endocrinology (1994) 143, 45–54