bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies
Authors: Garland H. O. , Atherton J. C. , Baylis C. , Morgan M. R. A. , Milne C. M.
Published: December 2008

Plasma samples were obtained throughout pregnancy and pseudopregnancy from Sprague–Dawley (SD) rats and during pregnancy from rats of the Munich Wistar (MW) strain. The concentrations of progesterone, oestradiol, prolactin, plasma renin activity (PRA), aldosterone and corticosterone were measured by radioimmunoassay to establish hormonal profiles in the two strains of rat.

Circulating progesterone concentrations in both strains of rat were significantly higher during pregnancy than in virgin controls, except at term in the SD group. The hormonal pattern for pseudopregnancy was similar to that of the first half of pregnancy. Oestradiol concentrations were similar to, or lower than, those in virgin controls throughout pseudopregnancy and for the first 2 weeks of pregnancy in both strains of rat. Increased concentrations of steroid were seen only in the pregnant groups towards term. In SD rats, highest prolactin concentrations were apparent during the first half of pregnancy and pseudopregnancy, and at term in the pregnant group. Pregnant MW rats showed a different profile for this hormone, with low levels throughout pregnancy except at term. In all groups PRA rose to a peak at day 9 and decreased to day 16. Pregnant SD rats also showed a significant increase at term. Aldosterone concentrations were significantly increased at several stages of pregnancy in both strains of rat, particularly during the second half of gestation. Pseudopregnant animals showed a different hormone profile, with no significant changes until day 16 when lower concentrations were recorded. There was little variation in the circulating corticosterone concentration except in pregnant rats at term when levels fell.

These findings are discussed in relation to the known renal changes of pregnancy and pseudopregnancy.

J. Endocr. (1987) 113, 435–444
Prostaglandin production by the guinea-pig endometrium: is calcium necessary?
Authors: Riley S. C. , Poyser N. L.
Published: December 2008

The output of prostaglandin (PG) F2α from guinea-pig endometrium obtained on day 15 of the oestrous cycle and maintained in tissue culture was significantly (P<0·05) reduced by the use of Ca2+-depleted medium, EGTA (a Ca2+ chelator), 8-(N,N-diethyl-amino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8; an intracellular Ca2+ antagonist), trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7; both calmodulin antagonists). Nifedipine inhibited PGF2α output at a concentration (100 μmol/l) much greater than that usually required to block Ca2+ channels. Verapamil had a small but significant (P < 0·05) inhibitory effect on PGF2α output at 10–100 μmol/l. The outputs of PGE2 and, to a lesser extent, 6-keto-PGF1α (the hydrated product of PGI2) were also reduced by using Ca2+-depleted medium. EGTA reduced the outputs of PGE2 and 6-keto-PGF1α on day 1 of culture, but stimulated 6-keto-PGF1α output on day 3 of culture. The outputs of PGE2 and 6-keto-PGF1α were increased by TMB-8 (100 μmol/l) on day 3 of culture and by TFP and, to a smaller extent, by W-7 on all 3 days of culture. Nifedipine (100 μmol/l by not 1 or 10 μmol/l) reduced the outputs of PGE2 and 6-keto-PGF1α on all 3 days of culture, whereas verapamil (100 μmol/l but not 1 or 10 μmol/l) increased the outputs of these two prostaglandins on days 2 and 3 of culture. Phorbol 12-myristate 13-acetate (an activator of protein kinase C) had no effect on the outputs of PGF2α, PGE2 and 6-keto-PGF1α from cultured guineapig endometrium obtained on days 7 and 15 of the oestrous cycle. It is concluded that extracellular Ca2+ is necessary for the high output of PGF2α from the guinea-pig uterus after day 11 of the oestrous cycle, and that the action of Ca2+ is not potentiated by the activation of protein kinase C.

J. Endocr. (1987) 113, 463–471
Effects of metyrapone and etomidate on adrenal function and growth rate in female rats
Authors: Sillence M. N. , Rodway R. G.
Published: December 2008

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

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

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

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

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

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

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

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

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

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

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

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

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
Role of prolactin in a pheromone-like sexual inhibition in the male lesser mouse lemur
Authors: Perret M. , Schilling A.
Published: December 2008

Sexual activity of the male lesser mouse lemur can be induced by a long photoperiod, and plasma testosterone concentrations increase from 20 to 220 nmol/l within 3 weeks of photoperiodic stimulation. When isolated males were exposed to the volatile compounds from the urine of an active dominant male for 4 weeks at the beginning of the long daylight period, they demonstrated a significant decrease in testosterone concentrations (134± 11 nmol/l) compared with controls (210 ± 26 nmol/l) within 2 weeks. Lowering concentrations of prolactin by daily injections of bromocriptine prevented the decrease in testosterone in males simultaneously exposed to the odorant stimulation. Increasing concentrations of prolactin by daily injections of sulpiride mimicked the effect of the odorant stimulation in males receiving only fresh non-odorized air. The decrease in testosterone was strengthened when sulpiride was administered concurrently with exposure to urine. These results support the conclusion that variations in the concentration of prolactin are involved in the neuroendocrinological process mediating the pheromone-like sexual inhibition in the male lesser mouse lemur. However, daily injections of bromocriptine in males which were photoperiodically stimulated but not exposed to dominant male urine odour, also induced a significant decrease in testosterone concentrations. This finding suggests that two different systems involving prolactin and leading to opposite effects might be implicated in the regulation by environmental factors of sexual activity in the male lesser mouse lemur.

J. Endocr. (1987) 114, 279–287
Plasma concentrations of ovarian steroids in the freshwater European silver eel (Anguilla anguilla L.): effects of hypophysectomy and transfer to sea water
Authors: Quérat B. , Nahoul K. , Hardy A. , Fontaine Y. A. , Leloup-Hâtey J.
Published: December 2008

Intact and hypophysectomized freshwater (FW) silver eels were transferred to tanks of FW or artificial sea water (SW; salinity = 0·60 osmol/l) which were simultaneously renewed twice a week. Fish were killed 2 months after transfer and plasma was assayed for ovarian steroids.

In all fish, 5α-androstane-3β,17β-diol was present, while 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol were undetectable.

In intact FW eels, plasma levels of testosterone, 5α-androstane-3β,17β-diol and oestradiol-17β were approximately 0·15 nmol/l. In intact SW eels, no change in plasma levels of testosterone and 5α-androstane-3β,17β-diol was found, whereas the concentration of oestradiol-17β was increased significantly (P<0·01), indicating stimulation of aromatase activity.

In hypophysectomized compared with intact FW fish, plasma levels of testosterone and 5α-androstane-3β,17β-diol were decreased (P<0·05) and there was a slight but significant (P<0·01) augmentation of the plasma concentration of oestradiol-17β which may have involved the removal of pituitary-dependent inhibition of aromatase activity, possibly by 5α-reduced compounds.

In hypophysectomized compared with intact SW fish, plasma levels of testosterone, 5α-androstane-3β,17β-diol and oestradiol-17β were decreased (P<0·05); in the case of oestradiol-17β, this may have reflected the diminished ovarian synthesis of testosterone, its precursor. The plasma level of oestradiol-17β was, however, higher in SW than in FW fish, even in hypophysectomized eels. This suggests that extra-pituitary mechanisms mediate, at least partly, the effects of transfer to SW on aromatase activity.

J. Endocr. (1987) 114, 289–294
Scanning electron microscopy of postovulatory human endometrium in spontaneous cycles and cycles stimulated by hormone treatment
Authors: Martel D. , Frydman R. , Glissant M. , Maggioni C. , Roche D. , Psychoyos A.
Published: December 2008

The ultrastructure of the luminal surface epithelium was compared in endometrial samples taken from 23 normally cycling women and from 22 patients submitted to ovarian stimulation with clomiphene citrate (100 mg/day for 5 days), human menopausal gonadotrophin (hMG) and human chorionic gonadotrophin (hCG). On day 2 after ovulation, only four out of nine specimens taken from the women in the hormone-treated group were identical to those of normally cycling women. On day 6 after ovulation, only two out of the 13 biopsy specimens from the treated group were the same as those from normally cycling women at that stage. Apical protrusions (pinopodes), typical for this period of the cycle, were missing in 11 of the 13 endometrial samples from the treated group.

These observations suggest that the hormonal treatment applied to induce ovulation (clomiphene citrate, hMG and hCG) can modify the normal development of the prenidatory endometrium, and may thus have a negative effect on the rate of egg implantation.

J. Endocr. (1987) 114, 319–324
Changes in concentration of human atrial natriuretic peptide in normal pregnancy and toxaemia
Authors: Otsuki Y. , Okamoto E. , Iwata I. , Nishino E. , Mitsuda N. , Mori M. , Takagi T. , Sugita N. , Tanizawa O.
Published: December 2008

Changes in concentration of human atrial natriuretic peptide (hANP) in normal and toxaemic pregnancy were examined. The maternal plasma concentration of hANP increased gradually during normal pregnancy to a maximum of 20·0±2·4 pmol/l (mean ± s.e.m.) after week 36 of pregnancy. From week 20, the plasma concentrations of hANP were significantly higher than those in non-pregnant women (9·3±2·0 pmol/l). In toxaemia with hypertension, maternal plasma hANP levels were increased after week 26 of pregnancy (37·7±6·0 pmol/l) compared with those in normal gravida at the same time (17·1±1·6 pmol/l). Maternal plasma hANP levels in toxaemia only with oedema were not different from those in normal gravida.

J. Endocr. (1987) 114, 325–328
In-vivo evaluation of dopamine receptor-mediated inhibition of gonadotrophin secretion from the pituitary gland of the goldfish, Carassius auratus
Authors: Omeljaniuk R. J. , Shih S. H. , Peter R. E.
Published: December 2008

Dopamine acts directly on the pituitary to modulate gonadotrophin (GtH) secretion in goldfish (Carassius auratus). In the light of this important role for dopamine in the regulation of goldfish reproduction, this investigation was designed to evaluate the receptor specificity of this dopamine inhibition and to describe the use of domperidone, a specific dopamine D2-receptor antagonist, in the manipulation of pituitary function in goldfish. To investigate the specificity of dopamine inhibition of GtH secretion, selected dopamine receptor antagonists were injected i.p. to block dopamine receptors thereby increasing GtH secretion as reflected by increased serum concentrations of GtH. Serum GtH levels were significantly increased by the active stereoisomer (−)-sulpiride in a dose-related fashion; (+)-sulpiride had no effect. Comparison of dopamine antagonists at low doses indicated that only domperidone and pimozide caused significant increases in serum concentrations of GtH. Dopamine antagonists potentiated the action of a gonadotrophin-releasing hormone analogue (GnRH-A) with an order of potency of domperidone = pimozide > metoclopramide = fluphenazine. [3H]Domperidone, injected i.p. with unlabelled domperidone, entered the blood and achieved maximum concentrations 12 h after injection, but did not accumulate in the brain in appreciable amounts. Gonadal 3H radioactivity was usually equal to or in excess of blood radioactivity, while [3H]domperidone was highly concentrated in the pituitary in a time-dependent fashion, with maximal accumulation occurring 24 h after injection. The time-course of pituitary accumulation of [3H]domperidone correlated well with the temporal increase in serum GtH levels in response to i.p. injected domperidone or domperidone plus an analogue of LHRH. Domperidone increased serum concentrations of GtH in a dose-related fashion; an analogue of salmon GnRH (sGnRH-A) increased the sensitivity and magnitude of the serum GtH response to domperidone. Serum concentrations of GtH were increased by sGnRH-A in a dose-related fashion; a low dose of domperidone substantially increased the sensitivity of the serum GtH response to sGnRH-A.

These results indicate that dopamine inhibits GtH secretion from the goldfish pituitary by acting through a specific mechanism mediated by a dopamine D2 receptor. Domperidone increased serum concentrations of GtH, potentiated the action of gonadotrophin-releasing hormones and did not pass into the brain after i.p. injection into goldfish. The data also suggest that dopamine and GnRH, although acting through different receptors, influence the effect of each other on GtH release.

J. Endocr. (1987) 114, 449–458
Adult rat Sertoli cells secrete a factor or factors which modulate Leydig cell function
Authors: Papadopoulos V. , Kamtchouing P. , Drosdowsky M. A. , de Reviers M. T. Hochereau , Carreau S.
Published: December 2008

Production of testosterone and oestradiol-17β by Leydig cells from adult rats was stimulated by LH or dibutyryl cyclic AMP (10 and 2·5-fold respectively). The addition of spent medium from normal, hemicastrated or γ-irradiated rat seminiferous tubule cultures, as well as from Sertoli cell cultures, to purified Leydig cells further enhanced both basal (44 and 53% for testosterone and oestradiol-17β respectively) and LH-stimulated (56 and 18%) steroid output. Simultaneously, a decrease (20–30%) in intracellular cyclic AMP levels was observed. This stimulating factor (or factors) secreted by the Sertoli cells is different from LHRH, is of proteinic nature and has a molecular weight ranging between 10 000 and 50 000; its synthesis is not controlled by FSH nor by testosterone. This factor(s) involved in rat Leydig cell steroidogenesis, at a step beyond the adenylate cyclase, does not require protein synthesis for testosterone formation whereas it does for oestradiol-17β production. It should be noted that a germ cell–Sertoli cell interaction modulates the synthesis of this factor(s).

J. Endocr. (1987) 114, 459–467
Diurnal rhythm of vasopressin but not of oxytocin in the cerebrospinal fluid of the goat: lack of association with plasma cortisol rhythm
Authors: Seckl J. R. , Lightman S. L.
Published: December 2008

Diurnal rhythms in the concentrations of vasopressin (AVP) and oxytocin in cerebrospinal fluid (CSF) differ between species and are unrelated to changes in the levels of these hormones in the peripheral circulation. We have investigated neurohypophysial hormone rhythms in the CSF of the conscious goat by determining whether they are entrained by daily cycles of light and darkness and by assessing the effect of the suppression of plasma cortisol.

Goats were implanted with cisternal cannulae under halothane anaesthesia and allowed to recover. They were accustomed to a 12 h light:12 h darkness lighting cycle (lights on from 07.30 to 19.30 h). After initial serial CSF and plasma sampling the daily cycle of light and darkness was reversed. Three goats were kept in constant light for 8 days before the study and five were given dexamethasone (5 mg/12 h) for 4 days.

There was a significant (P < 0·01) diurnal variation in CSF concentrations of AVP, with a maximum of 3·6 ± 0·8 (s.e.m.) pmol/l at 12.00 h and a minimum of 1·4 ± 0·3 pmol/l at 24.00 h. There were no significant changes in CSF concentrations of oxytocin or plasma AVP. After the light:darkness cycle was reversed the AVP rhythm in the CSF was disrupted after 24 h and reversed after 8 days. The diurnal rhythm of AVP in CSF persisted in animals exposed to constant light. After treatment with dexamethasone plasma cortisol was suppressed and showed no diurnal rhythm but the AVP rhythm in CSF remained unchanged.

J. Endocr. (1987) 114, 477–482
Cell kinetics of thyroid epithelial cells during hyperplastic goitre involution
Authors: Rognoni J. B. , Penel C. , Golstein J. , Galand P. , Dumont J. E.
Published: December 2008

Thyroid epithelial cell kinetics were investigated in rats when a normal iodine diet was re-established after a long period of iodine deficiency supplemented with propylthiouracil (0·15%) for the last 2 months. In the first (prelabelling) experiment, all rats were labelled with a single injection of [3H]thymidine 2 days before iodine refeeding in order to follow the fate of the prelabelled cells. In the second experiment, the pulse-labelling index at the time of killing was measured; for this purpose the rats received [3H]thymidine 1 h before death. In these two experiments autoradiography was performed on histological sections. Thyroids were excised on day 0 and then at various intervals up to day 73 of iodine refeeding.

Plasma tri-iodothyronine (T3) and thyroxine (T4) were very low until day 4 and then increased to reach control values on day 30. Thyroid concentration of iodide rose to 20 times the value on day 0, remained at this high level until day 2, and then diminished on day 4 to reach the control value on day 16. Plasma TSH concentrations were very high in iodine-deficient rats and did not vary significantly until day 8, when they fell rapidly to reach the control value on day 30. Thyroid weight, raised on day 0, decreased relatively quickly until day 4, then more slowly until day 30. Total thyroid epithelial cell number, high on day 0 (30·7 ×106 cells) was constant until day 16, then decreased until day 30 at which time a plateau was reached. In the prelabelling experiment, the fraction of labelled cells was high on day – 2 and doubled after 24 h because of division of the labelled cells. On day 1 after iodine refeeding this parameter decreased significantly and continued to decrease until day 16 at which time a minimum value was obtained. The mean number of silver grains per labelled nucleus decreased very slowly from 0 until day 73. The per cent of labelled and unlabelled thyroid epithelial cells in well-defined follicles was low until day 8 and increased progressively thereafter, reaching the control value on day 45. On the other hand, the pulse-labelling index on days 0 and 1 was similar to that measured on day – 2; already high on day 0, it increased markedly on day 2 (3·30 ± 0·57%), decreased abruptly on day 4, and reached the control value on day 8 (0·07 ± 0·02%).

It is suggested that (1) cell death during early hyperplastic goitre involution reactivates the thyroid epithelial cells to proliferate; this phenomenon is independent of T3, T4 and TSH but clearly depends on iodide action, and it does not play a major role in goitre involution; (2) the restructuring of the gland, i.e. follicle growth, is not only achieved by newly formed cells but also by pre-existing cells (prelabelling experiment); and (3) maintenance of a large thyroid epithelial cell population, even after a long period of iodine refeeding, is the consequence of a relatively long life-span (73 days or more) of the pre-existing cell population.

J. Endocr. (1987) 114, 483–490
Immunohistochemical localization of relaxin, prolactin and prostaglandin synthase in human amnion, chorion and decidua
Authors: Bryant-Greenwood G. D. , Rees M. C. P. , Turnbull A. C.
Published: December 2008

Relaxin, prolactin and prostaglandin synthase were localized by the avidin-biotin immunoglucose oxidase method in human amnion, chorion and decidua. Specimens from ten normal spontaneous deliveries and four elective Caesarean section deliveries with no labour were compared. Relaxin was found more consistently in the cells of the chorionic cytotrophoblast than in the cells of the parietal decidua adherent to the fetal membranes. Only half the tissues after spontaneous delivery contained positive relaxin-stained cells, whereas all the tissues from elective Caesarean sections contained cells positively stained with antiserum to relaxin. In both series of tissues prolactin was localized predominantly in the parietal decidual cells and was very infrequently found in the chorionic cytotrophoblast. Polyclonal antiserum to prostaglandin synthase was used to identify those cells producing prostaglandin in amnion, chorion and decidua. The cells of the amnion and chorion showed positive immunolocalization with no differences between tissues collected before or after labour. Double immunostaining using avidin-biotin immunoperoxidase for prolactin, followed by avidin-biotin immunoglucose oxidase for prostaglandin synthase, produced identical results in the same series of tissues examined with the single-staining method.

J. Endocr. (1987) 114, 491–496
Significance of the calcium content of mouse β cells in the preservation of glucose-induced insulin release during culture
Authors: Bergsten P.
Published: December 2008

Pancreatic islets containing more than 90% β cells from obese–hyperglycaemic (ob/ob) mice were cultured for 3 days in different concentrations of Ca2+ and glucose to evaluate the importance of intracellular Ca2+ sequestration in glucose-induced insulin release. The islet contents of calcium (total and exchangeable) and immunoreactive insulin were compared with the insulin secretory response to glucose after culture. The turnover of Ca2+ increased with increasing concentrations of glucose and Ca2+. Islets cultured in the presence of 5.5 mmol glucose/1 contained more calcium and insulin than those cultured with 1 or 20 mmol glucose/1. During culture in 20 mmol glucose/1, a lowering of the Ca2+ concentration of the medium from 0.42 to 0.025 mmol/l resulted in a paradoxical increase in intracellular calcium, with improvement of the subsequent secretory response to the sugar. When the islets had been exposed to the calcium channel blocker D-600 during culture in a Ca2+-deficient medium, substantial insulin release was noted from islets containing relatively small amounts of calcium. The results suggest that the well-established role of glucose in maintaining insulin release is associated with an ability of the sugar to stimulate the retention of calcium in β cells.

J. Endocr. (1987) 115, 27-34
Arginine vasopressin and oxytocin in the bovine adrenal gland
Authors: Nussey S. S. , Prysor-Jones R. A. , Taylor A. , Ang V. T. Y. , Jenkins J. S.
Published: December 2008

The concentrations of immunoreactive oxytocin and arginine vasopressin (AVP) and their respective neurophysins (NpI and NpII) were compared in bovine adrenal cortex and medulla. While the concentration of AVP was similar in both tissues there was more NpII in the medulla. The medulla also contained much more oxytocin and NpI than the cortex. The extracted AVP and oxytocin had identical retention times to those of the synthetic peptides on high-performance liquid chromatography (HPLC) and were biologically active in assays for antidiuretic and milk-ejection activity (with potencies of 310 units/mg and 340 units/mg respectively). Adrenal NpI and NpII behaved identically to commercially available neurohypophysial proteins on HPLC.

Oxytocin, NpI and AVP were assayed in five subcellular fractions of bovine adrenal medulla prepared on discontinuous sucrose gradients. A high proportion of each co-localized with noradrenaline and adrenaline in the chromaffin granule fraction.

Binding of [3H]AVP and [3H]oxytocin to crude bovine adrenal medulla membranes was dependent upon both time and temperature. The binding sites were specific and saturable: studies with the V1 AVP antagonist d(CH2)5Tyr(Me)AVP and the V2 agonist 1-deamino-8-d-AVP indicated that the AVP receptor was V1 in specificity. Scatchard plots showed that each ligand interacted with a single high-affinity, low-capacity binding site: oxytocin dissociation constant (Kd) 3·1 ±0·29 nmol/l, maximum binding capacity (Bmax) 89·6 ±18·4 fmol/mg protein (n = 3); AVP Kd 0·73 ±0·02 nmol/l, Bmax 26·5 ±8·3 fmol/mg protein (n = 3).

Oxytocin and AVP had no effect on basal catecholamine release from bovine chromaffin cells in primary monolayer culture. However, both peptides inhibited acetylcholine- or nicotine-stimulated noradrenaline and adrenaline release in a dose-related manner. Neither inhibited noradrenaline or adrenaline secretion stimulated by veratridine- or potassium-induced depolarization.

We conclude that the bovine adrenal cortex and medulla contain authentic AVP and oxytocin. In the medulla the peptides are packaged in secretory granules. The presence of the related neurophysins and high-affinity receptors in the medulla suggests that the peptides are both synthesized and have their site of action within this tissue. The function of AVP and oxytocin in the medulla may be indicated by the inhibition of acetylcholine-stimulated catecholamine secretion in vitro, although the effect requires high concentrations of either peptide.

J. Endocr. (1987) 115, 141–149