bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of metyrapone and etomidate on adrenal function and growth rate in female rats
Authors: Sillence M. N. , Rodway R. G. 
Published: December 2008

ABSTRACT
Two inhibitors of adrenal steroidogenesis were examined to determine whether the growth rate of female rats could be improved by lowering circulating plasma corticosterone concentrations.
The first inhibitor, etomidate, is a potent narcotic agent and was found to have no effect on plasma corticosterone and deoxycorticosterone (DOC) concentrations at sub-narcotic doses. Growth rate, food intake, food conversion efficiency and adrenal weight were also unaffected by the drug.
The second inhibitor, metyrapone, was shown in acute studies to have two distinct actions. In 6-week-old female rats moderate doses of metyrapone (50 mg/kg) had a stimulatory action resulting in increased plasma DOC and corticosterone concentrations. Higher doses of metyrapone (150–300 mg/kg) were increasingly less selective, causing an increase in plasma concentration of DOC, but attenuating the increase in corticosterone concentration, presumably by inhibiting the 11β-hydroxylase enzyme which allows the conversion of DOC to corticosterone. In adult rats (>12 weeks old) the classical response to metyrapone was observed. Plasma DOC concentrations were increased, while corticosterone levels were reduced in a dose-dependent manner.
In 5-week-old rats treated chronically, metyrapone (300 mg/kg) had no effect on plasma corticosterone, but increased plasma DOC concentration, depressed food intake and reduced growth rate. In 8-week-old rats treated chronically, the high dose of metyrapone (300 mg/kg) required to lower peak plasma corticosterone concentrations produced toxic effects resulting in the death of three animals. The remaining animals recovered rapidly, and gained more weight than controls over the final 6 days of the experiment. However, this experiment was terminated before the treated animals were able to catch up with the controls.
Inverse correlations were found between both plasma corticosterone and DOC concentrations and growth rate, confirming that growth may be retarded by the glucocorticoids and that inhibition of their production may be of potential use in stimulating growth. Neither of the agents tested in the present study, however, are likely to be future candidates as growth promoters.
J. Endocr. (1987) 113, 473–478
Tumour promoter 12-O-tetradecanoylphorbol 13-acetate and epidermal growth factor stimulate proliferation and inhibit differentiation of porcine thyroid cells in primary culture
Authors: Takasu N. , Shimizu Y. , Yamada T. 
Published: December 2008

ABSTRACT
12-O-Tetradecanoylphorbol 13-acetate (TPA) is a potent tumour promoter and shows several biological activities of epidermal growth factor (EGF). EGF and TPA stimulated proliferation and inhibited differentiation of porcine thyroid cells in primary culture. They also stimulated [3H]thymidine incorporation and inhibited an early step in thyroid hormone synthesis (iodine organification). The results indicate that EGF and TPA switch the developmental course of porcine thyroid cells from differentiation to proliferation.
J. Endocr. (1987) 113, 485–487
ICI 176,334: A NOVEL NON–STEROIDAL, PERIPHERALLY SELECTIVE ANTIANDROGEN
Authors: Furr B.J.A. , Valcaccia B. , Curry B. , Woodburn J.R. , Chesterson G. , Tucker H. 
Published: December 2008

ABSTRACT
Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic–pituitary axis, which leads to an increase in LH and testosterone secretion. A new non–steroidal antiandrogen ICI 176,334 ((2RS)4′-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3′-trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200μg/kg) for 7 days to immature castrated rats, ICI 176,334 (10mg/kg) significantly (P<0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25mg/kg for 14 days to adult rats caused a dose–related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen–responsive benign and malignant diseases.
Barium-induced LH release from chicken pituitary cells: synergism with phorbol ester
Authors: Davidson J. S. , Wakefield I. , King J. A. , Millar R. P. 
Published: December 2008

ABSTRACT
Barium is known to elicit secretion in a number of cell systems. The mechanism of Ba2+ stimulation of LH release in cultured chicken pituitary cells was investigated in the present study. Barium-stimulated LH release was inhibited by extracellular Ca2+, indicating that Ba2+ does not act by stimulating Ca2+ entry. Simultaneous stimulation of the cells with Ba2+ and phorbol ester produced a synergistic response, similar to the synergism obtained with phorbol ester and treatments which increase cytosolic Ca2+. Both Ba2+-stimulated LH release and the synergism of Ba2+ with phorbol ester were inhibited by calcium channel blockers (Co2+, methoxyverapamil and nifedipine) and by calmodulin antagonists (trifluoperazine and chlorpromazine). These results indicate that the actions of Ba2+ are dependent on its entry through Ca2+ channels, and suggest that calmodulin activation is necessary for the synergism between Ba2+ and phorbol ester. Thus, synergism does not result from a direct effect of divalent cations on C-kinase.
J. Endocr. (1987) 114, 11–16
Plasma patterns of LH, FSH and prolactin in rats with a polycystic ovarian condition induced by oestradiol valerate
Authors: Grosser P. M. , McCarthy G. F. , Robaire B. , Farookhi R. , Brawer J. R. 
Published: December 2008

ABSTRACT
The patterns of plasma LH, FSH and prolactin concentrations were investigated in rats with a polycystic ovary condition (PCO). The condition was induced by treatment with oestradiol valerate 9 weeks before blood sampling. Serial blood samples were taken at 10-min intervals for 4 h from ten rats with PCO. All samples were assayed for LH, those from five animals for FSH and those from the remaining five animals for prolactin. In addition, five control animals with normal oestrous cycles were sampled during oestrus and the samples assayed for LH. Mean concentrations of LH, FSH and prolactin in rats with PCO were 140 ng/l, 76 μg/l and 7·6 μg/l respectively. All three hormones exhibited an episodic pattern. The mean peak amplitudes of LH, FSH and prolactin were 120 ng/l, 25 μg/l and 3·5 μg/l respectively. All three hormones exhibited a similar mean frequency of four or five episodes per 4 h. The LH and FSH patterns were closely synchronized; nearly all FSH peaks coincided with LH peaks. The prolactin pattern did not, however, correlate with that of the gonadotrophins. Despite the persistent oestrous condition of the animals with PCO, it was clear that their pattern of LH did not resemble that of cyclic animals in normal oestrus; in the normally cyclic animals in oestrus the pulse period was nearly twice as long and the pulse amplitude was more than sixfold greater than those in animals with PCO. We conclude that the unique episodic patterns of gonadotrophins are more important than mean blood concentrations of these hormones in establishing and maintaining the polycystic ovary syndrome.
J. Endocr. (1987) 114, 33–39
Effect of the gonadotrophin surge at pro-oestrus on steroidogenesis and gonadotrophin binding of preantral follicles in the cyclic hamster
Authors: Krishna A. , Terranova P. F. 
Published: December 2008

ABSTRACT
The present study describes the acute changes in steroids and human chorionic gonadotrophin (hCG) and FSH binding of preantral follicles induced by the gonadotrophin surges on the day of pro-oestrus. Preantral follicles were isolated by microdissection before (09.00–10.00 h), during (15.00–16.00 h) and after (21.00–22.00 h) the LH surge on pro-oestrus. Follicles at each time-period were pooled and steroid concentrations and gonadotrophin receptors determined. Before the LH surge, concentrations of progesterone and androstenedione were 40·8 ± 6·1 (s.e.m.) and 10·7 ± 3·9 fmol/follicle respectively. At the peak of the LH surge, progesterone and androstenedione concentrations in preantral follicles increased to 848 ± 186 and 129 ± 33 fmol/follicle respectively. Immediately after the LH surge, progesterone increased to 1238 ±97 fmol/follicle whereas androstenedione declined to 13·3 ±2·1 fmol/follicle. Oestradiol was less than 6 fmol/follicle throughout these periods. Binding of hCG and FSH to preantral follicles increased after the surge (hCG, 56± 2·6 c.p.m./follicle; FSH, 29·8 ± c.p.m./follicle) when compared with values obtained before the surge (hCG, 15·8± 4·0 c.p.m./follicle; FSH, 14·1 ± 1·9 c.p.m./follicle). Also, hCG binding increased significantly (P<0·05) from 09.00 to 21.00 h (56 ±2·6 c.p.m./follicle).
In order to ascertain which follicular compartments were affected by the LH and FSH surges on pro-oestrus, granulosa cells and thecae from preantral follicles were isolated and steroid concentrations and LH and FSH binding measured. Both thecal and granulosal concentrations of androstenedione were significantly (P<0·01) higher at the peak of the LH surge (15.00 h) than at 09.00 h (before the surge) and 21.00 h (after the surge). The granulosal concentration of progesterone was lowest at 09.00 h, highest at 15.00 h and remained increased at 21.00 h. Thecal progesterone concentrations did not increase significantly until 21.00 h at pro-oestrus. Binding of hCG to theca increased significantly (P<0·01) at 15.00 and 21.00 h when compared with values at 09.00 h. Binding of FSH to theca was not detected at 09.00 h and was low at 15.00 and 21.00 h. Binding of hCG and FSH to granulosa cells did not change significantly throughout this period on pro-oestrus.
These results indicate that the gonadotrophin surges on pro-oestrus induce significant stepwise increases in thecal LH binding in preantral follicles and that these coincide with parallel increases in follicular progesterone. Thus the gonadotrophin surges on pro-oestrus may be a signal regulating the onset of steroidogenesis and growth of preantral follicles.
J. Endocr. (1987) 114, 49–54
Relationships between LH stimulation in vitro and progesterone, androstenedione and cyclic AMP synthesis in preantral follicles of the cyclic hamster
Authors: Krishna A. , Terranova P. F. 
Published: December 2008

ABSTRACT
In-vivo changes in steroidogenesis in preantral hamster follicles following exposure to the LH surge could be mimicked by stimulation with exogenous LH in vitro. Luteinizing hormone given only during the first hour (media were changed every hour) of a 6-h incubation promptly increased the concentration of androstenedione and adenosine 3′:5′-monophosphate (cAMP) in the media and this was followed by a gradual decline to <20% of the peak value; progesterone in media was not detectable with a single LH stimulation. However, LH given every hour increased progesterone and cAMP concentrations in the media throughout the period of incubation, but the transient increase and subsequent decline in androstenedione was still observed. The decline in androstenedione release by preantral follicles was apparently due to a lack of steroid precursor and not to either inhibition of hydroxyl-lyase or lack of LH or cAMP stimulation. Exogenous dibutyryl cAMP (dbcAMP) and 8-Br-cAMP mimicked the effects of LH on the pattern of follicular androstenedione release into the media; however, dbcAMP and 8-Br-cAMP did not increase concentrations of progesterone in vitro. In preantral follicles, LH stimulated cAMP release into the media and apparently inhibited phosphodiesterase activity, since methyl isobutylxanthine (MIX) did not potentiate the effect of LH on cAMP. Follicle-stimulating hormone also increased androstenedione and cAMP in the media of the preantral follicles in a manner similar to that of LH, except that between 4 and 6 h of incubation the release of androstenedione and cAMP was less than that produced by stimulation with LH. Interestingly, FSH and MIX stimulated androstenedione and cAMP release by preantral follicles in a manner similar to that induced by LH alone.
These results indicate that LH stimulation of preantral follicles in vitro induces an androstenedione– progesterone shift which is mediated by cAMP. The decline in androstenedione release by the preantral follicle in vitro appears to be due to a lack of appropriate steroid precursors and not to an inhibitory action of LH on androgen synthesis.
J. Endocr. (1987) 114, 55–63
Effect of small doses of bovine follicular fluid on the tonic secretion of gonadotrophins in the ewe
Authors: Martin G. B. , Taylor P. L. , McNeilly A. S. 
Published: December 2008

ABSTRACT
Previous work has shown that treatment of ewes with steroid-free bovine follicular fluid (bFF), a rich source of inhibin, partially inhibits the increase in mean plasma concentrations of LH induced by ovariectomy. The present experiment was designed to test the hypothesis that this effect was a reflection of reduced LH pulse amplitude which would only be expressed at high (pharmacological) doses of bFF. To do this, we assessed the dose–response to bFF of the secretion of FSH and LH pulses in intact and acutely ovariectomized ewes.
In intact ewes, a low dose of bFF (0·2 ml s.c. every 8 h) had no detectable effect on the secretion of FSH, an intermediate dose (0·6 ml s.c. every 8 h) depressed FSH concentrations for about 24 h and a high dose (1·8 ml s.c. every 8 h) reduced FSH concentrations to undetectable levels. In ewes treated with 1·8 ml bFF, FSH concentrations also remained undetectable after ovariectomy and did not increase until treatment was withdrawn. In ewes treated with 0·6 ml bFF, FSH concentrations were maintained at normal intact levels for about 32 h following ovariectomy but then rose to normal ovariectomized levels. In ewes treated with 0·2 ml bFF, FSH concentrations increased immediately after ovariectomy but more slowly than in control ovariectomized ewes. Profiles of LH pulses were recorded after ovariectomy, during and after the withdrawal of bFF treatment. In ewes treated with the highest dose (1·8 ml s.c. every 8 h), mean LH levels and pulse amplitude were lower than in control ewes and increased significantly following withdrawal of treatment. None of the other pulse variables measured (apparent half-life, pulse interval, nadir) were significantly affected. The lower doses did not significantly affect LH secretion.
It was concluded that FSH secretion can be inhibited for short periods by low doses of inhibin and that a dose of 0·6 ml bFF every 8 h is approximately equivalent to normal ovarian output. However, another factor, possibly oestrogen, is also involved in the long-term regulation of plasma FSH concentrations. The inhibitory effect of bFF on LH pulse amplitude was only observed at the highest dose, suggesting that it is a pharmacological effect and that it is unlikely that inhibin plays a major role in the control of tonic LH secretion.
J. Endocr. (1987) 114, 73–79
The use of reversed-phase high-performance liquid chromatography to detect proteolytic activity from human pancreas in a radioimmunoassay for corticotrophin-releasing factor
Authors: Jessop D. S. , Patience R. L. , Cunnah D. , Rees L. H. 
Published: December 2008

ABSTRACT
Degradation of tracer during a radioimmunoassay (RIA) can result in false-positive concentrations of immunoreactivity being reported in a biological sample. A technique has been developed using reversed-phase high-performance liquid chromatography (HPLC) to detect proteolytic degradation of corticotrophin-releasing factor-41 (CRF-41) during incubation with tissue extracts under RIA conditions. Human pancreatic tissue was extracted in HCl or urea and incubated with 125I-labelled CRF-41 at neutral pH for 18 h. When samples were analysed by HPLC and fractions counted for radioactivity, tracer was extensively degraded. Heating extracts at 85 °C or adding lima bean trypsin inhibitor to the medium prevented degradation. Pancreatic tissue extracted in HCl was analysed by gel filtration and HPLC, and fractions were subjected to RIA for CRF-41. A peak of immunoreactivity was detected by both chromatographic methods. However, when this material was incubated with tracer and analysed by HPLC, the tracer was degraded, indicating that proteolytic activity remained after acid extraction and two forms of chromatography.
J. Endocr. (1987) 114, 147–151
Release of big and small molecular forms of prolactin: dependence upon dynamic state of the lactotroph
Authors: Torres A. I. , Aoki A. 
Published: December 2008

ABSTRACT
Secretion of different molecular forms of prolactin was studied from a multidisciplinary standpoint in three different experimental rat models which covered the broadest range of lactotrophic activity. The results obtained allowed the recognition of common secretory patterns in stimulated, inhibited and hyperstimulated lactotrophic activity.
Polymeric (big) prolactin is stored exclusively in membrane-bound secretory granules and appears to be a convenient biochemical marker with which to quantify the pool of hormone stored in the cell cytoplasm, while monomeric (small) prolactin represents a pool of newly synthesized hormone which is loosely coupled to organelles involved in its intracellular processing.
Most of the prolactin in stimulated lactotrophs is processed through a regulated pathway and the hormone released by exocytosis of secretory granules. Interruption of stimulation resulted in accumulation of secretory granules and polymeric prolactin. In hyperstimulated lactotrophs the polymerization and aggregation of prolactin into secretory granules was bypassed and most of the hormone released directly after its synthesis. The pattern of prolactin secretion could be closely correlated with the dynamic state of the lactotroph.
J. Endocr. (1987) 114, 213–220
Regulation of the corpus luteum of early pregnancy in the marmoset monkey: local interactions of luteotrophic and luteolytic hormones in vivo and their effects on the secretion of progesterone
Authors: Hearn J. P. , Webley G. E. 
Published: December 2008

ABSTRACT
The interaction between luteotrophic and luteolytic agents in controlling progesterone production by the marmoset corpus luteum in the late luteal phase/early pregnancy was investigated at the local level in vivo using a perfusion cannula system. Perfusion of the prostaglandin F2α(PGF2α) analogue, cloprostenol (0·5 μg/ml), resulted in an immediate fall in progesterone production. This response was not sustained in two out of five corpora lutea but pregnancy was terminated in all animals exposed to PGF2α. Perfusion of human chorionic gonadotrophin (hCG) (4 μg/ml) alone significantly stimulated progesterone secretion but there was no response to hCG when the corpus luteum had previously been perfused with PGF2α. Perfusion with hCG together with PGF2α prevented a fall in progesterone secretion. The results suggest that the luteolytic action of PGF2α in the marmoset may be to prevent luteotrophic support of the corpus luteum. Melatonin (860 pmol/l), perfused either with PGF2α or after PGF2α, stimulated progesterone production. The ability of melatonin to influence progesterone production by the primate corpus luteum may therefore be by both a direct luteotrophic action and the prevention of luteolysis. Application of the perfusion system in order to investigate the ability of deglycosylated hCG to antagonize the action of hCG at the corpus luteum showed the necessity of testing pure preparations of hormones.
J. Endocr. (1987) 114, 231–239
Stress-induced disruption of parturition in the rat may be mediated by endogenous opioids
Authors: Leng G. , Mansfield S. , Bicknell R. J. , Brown D. , Chapman C. , Hollingsworth S. , Ingram C. D. , Marsh M. I. C. , Yates J. O. , Dyer R. G. 
Published: December 2008

ABSTRACT
Plasma samples were obtained before and during parturition from conscious rats implanted chronically with a jugular cannula. Rats were either allowed to remain in their nesting cage throughout parturition, or were moved immediately following the birth of the second or third pup into an empty glass chamber. The time-course of parturition was prolonged for mother rats which were moved in mid-parturition to this unfamiliar environment. However, in rats given an i.v. injection of the opioid antagonist naloxone at the time of transfer, parturition followed a normal time-course, and plasma oxytocin levels were significantly higher than in animals injected with saline. Thus our hypothesis is that stress activates opioid pathways which delay parturition by inhibiting oxytocin release. Opioid-mediated mechanisms may similarly be responsible for some problems in human parturition.
J. Endocr. (1987) 114, 247–252
Relationship between oxytocin release and amplitude of oxytocin cell neurosecretory bursts during suckling in the rat
Authors: Meyer C. , Freund-Mercier M. J. , Guerné Y. , Richard Ph. 
Published: December 2008

ABSTRACT
Plasma concentrations of oxytocin and vasopressin were measured in relationship to oxytocin cell firing during suckling in urethane-anaesthetized rats.
Preliminary experiments showed that plasma concentrations of oxytocin and vasopressin, which were increased immediately after anaesthesia, reverted to basal concentrations 3 h later. Moreover, it was found that exogenous oxytocin had entirely disappeared 5 min after i.v. bolus injections of known doses of oxytocin.
Suckling did not modify the basal plasma concentration of oxytocin (14·6 ± 2·9 compared with 14·±61·5 pmol/l before suckling) except during a brief period immediately after neurosecretory bursts on oxytocin cells (37·8 ± 5·2 pmol/l; P < 0·001, n = 11). The plasma concentration of oxytocin did not differ significantly from the basal concentration 1·5 min later. The plasma concentration of vasopressin never varied.
After two neurosecretory bursts of similar amplitude (total number of spikes during the burst) recorded on the same oxytocin cell, the variations in plasma concentration of oxytocin were also similar. When, for a given cell, the amplitude of neurosecretory bursts increased or decreased, the amount of oxytocin released changed in the same way.
These data demonstrate (1) that suckling induces pulsatile release of oxytocin without vasopressin, and (2) a direct relationship between the amounts of oxytocin released and the amplitude of oxytocin cell neurosecretory bursts which argue in favour of simultaneous increases or decreases in the neurosecretory burst amplitudes on all oxytocin cells.
J. Endocr. (1987) 114, 263–270