bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress-induced prolactin release in female, male and androgenized rats: influence of progesterone treatment
Authors: Jahn G. A. , Deis R. P.
Published: December 2008

Ether stress applied at 10.00 h induced a 100% increase in serum prolactin in intact and ovariectomized androgenized rats. Ovariectomy significantly diminished the basal serum prolactin values observed in intact androgenized rats. Two doses of progesterone (5 mg) given to intact and ovariectomized androgenized rats 14 and 2 h before exposure to ether stress increased prolactin values in the control groups but completely prevented the effect of stress. Exposure to ether stress induced a 100% increase in serum prolactin values in androgenized rats with increased serum progesterone levels 4 days after the induction of ovulation and the luteal phase with human chorionic gonadotropin (hCG). A group of androgenized rats with induced maternal behaviour and which had been suckled for 6 days was given 100 i.u. hCG and suckled for another 6 days after the hCG-induced luteal phase had been established. The serum prolactin and progesterone values of these rats were significantly higher than those treated with hCG only and ether stress did not increase prolactin release. A greatly increased serum concentration of prolactin was obtained in pro-oestrous and oestrous virgin rats after exposure to ether stress. Serum prolactin was also increased by stress in male rats. Progesterone administration to these female and male rats prevented stress-induced prolactin release. To ascertain the part played by dopamine and serotonin in the effect of stress on prolactin release, groups of androgenized and oestrous female rats were treated with bromocriptine or p-chlorophenylalanine methylester hydrochloride (pCPA). The dopaminergic agonist bromocriptine markedly reduced prolactin levels in the unstressed androgenized rats, but did not prevent the prolactin increases induced by stress. Administration of pCPA had no effect on basal or stress-increased serum levels of prolactin. It is concluded that modifications of the ovarian steroid secretions, especially of progesterone, has profound effects on prolactin release in response to ether stress. The release of the hormone was not mediated by a dopaminergic or serotonergic regulatory pathway.

J. Endocr. (1986) 110, 423–428
Factors affecting prolactin secretion during the breeding cycle of the ring dove (Streptopelia risoria) and its possible role in incubation
Authors: Lea R. W. , Vowles D. M. , Dick H. R.
Published: December 2008

Plasma prolactin began to increase significantly about 5 days after the onset of incubation in both sexes of the dove to reach a peak at the time of hatch. At this time, the concentration of prolactin in the plasma of the female was significantly higher than in the male. In the middle of the incubation period prolactin levels measured over a 24-h period remained constant in both sexes, although the male sits during the middle of the day and the female for the rest of the time. Nest deprivation resulted in a sharp, significant decline in the concentration of prolactin in both sexes. Newly hatched squabs stimulated the release of prolactin only in those doves which had been incubating eggs for several days.

A distinct sex difference was observed in the expression of nest defence behaviour of the ring dove during the breeding cycle. At the time of laying, the female was significantly more aggressive than the male and her aggression increased only slightly up to the time of hatching. In contrast, male aggression increased gradually from a low level at laying to reach a peak at the time of hatching. The levels of plasma progesterone in the female showed a significant increase around the time of lay. No significant changes occurred in the plasma concentration of either progesterone or 17α-hydroxyprogesterone in the male.

Administration of prolactin increased the length of time of incubation of infertile eggs. Nest manipulations which had the effect of inducing the doves to begin incubation 4 days before laying showed that (1) the length of time of incubation of infertile eggs is fixed and independent of events which occur at courtship or oviposition, (2) the initiation of the increase in plasma prolactin concentration during incubation is independent of events which occur at courtship and oviposition and (3) the termination of incubation is always preceded by a fall in the concentration of plasma prolactin.

It is concluded that the length of time of incubation is dependent upon sustained raised levels of plasma prolactin. The concentration of plasma prolactin increases several days after the onset of incubation in response to the tactile stimulation of sitting. High levels, if maintained by visual stimulation from the nest, maintain incubation for a fixed period. After this, if the eggs fail to hatch, prolactin levels fall and the doves cease incubation and begin a new cycle.

J. Endocr. (1986) 110, 447–458
Role of sodium influx in thyrotrophin action: effects of the sodium channel agonist veratridine and thyrotrophin on radioiodine turnover and membrane potential in cultured porcine thyroid cells
Authors: Manley S. W. , Huxham G. J. , Bourke J. R.
Published: December 2008

Veratridine, a sodium channel agonist, depolarized cultured thyroid cells and increased the secretion of radioiodine from the organically bound pool. These effects were similar to those of TSH. Depolarization of the cells by increasing the potassium concentration of the medium failed to promote secretion, indicating that the sodium influx, rather than the depolarization itself, mediated the response. Veratridine, like TSH, also acutely reduced the cells' iodide uptake and inhibited the iodide transport pump. Unlike TSH, however, veratridine reduced, rather than increased, the fractional exit rate of iodide anion from the unbound pool. The data are consistent with the hypothesis that a sodium influx mediates some but not all of the actions of TSH on the thyroid gland, including the stimulation of secretion of thyroid hormones.

J. Endocr. (1986) 110, 459–466
Minimal effects of 17β-hydroxy-17α-methyl-estra-4,9,11-triene-3-one (R1881) on sexual behaviour in prepubertally castrated rams
Authors: Parrott R. F.
Published: December 2008

Ten adult prepubertally castrated rams were injected with 5α-dihydrotestosterone propionate (DHTP; 20 mg/day) for 3 weeks to stimulate genital development. Thereafter, half of the sheep were injected with testosterone (100 mg/day) for a further 4 weeks, while the remainder received the same dose of 17β-hydroxy-17α-methyl-estra-4,9,11-triene-3-one (methyltrienolone; R1881). All the animals were tested for sexual behaviour on 15 occasions with ovariectomized ewes in which oestrous behaviour was induced by injections of 50 μg oestradiol-17β benzoate at 4- to 5-day intervals. Behavioural tests were of 10 min duration and were carried out thrice weekly over a 5-week period, starting in the final week of DHTP treatment. Animals treated with testosterone showed a highly significant increase in courtship behaviour (tongue-flicks; lunges and nudges) after only four daily injections and this level of activity was maintained to the end of the experiment. However, the incidence of courtship activity in sheep treated with R1881 was similar to that recorded during the period of DHTP treatment. All animals given testosterone displayed mounts with pelvic thrusts and erections, and achieved intromission with ejaculation. These activities remained significantly more frequent than in sheep treated with R1881, starting from tests 9, 8 and 12 respectively. Four of the five individuals in the group given R1881 showed occasional mounts with thrusts, three showed sporadic erections and one sheep intromitted in the final test. These results indicate that, in contrast to the rat, R1881 has only very weak effects on sexual behaviour in the castrated ram.

J. Endocr. (1986) 110, 481–487
Social behaviour and testicular activity of juvenile rats
Authors: Taylor G. T. , Frechmann T. , Royalty J.
Published: December 2008

The juvenile stage of ontogeny is often characterized as a time of inactivity and quiescence for the immature reproductive system. The principle social behaviour by juveniles of many mammalian species is a rough-and-tumble activity known as play-fighting. An experiment is reported in which play-fighting by male rats was observed after various manipulations of gonadal steroids. Rats were housed in groups and castrated either on day 1 or day 10, times which are respectively during and after the sensitive period for androgeninduced organization of neural tissues in rats. Animals were injected with either 40 μg testosterone propionate or vehicle between 21 and 45 days of age, and play-fighting with unoperated, unfamiliar rats was examined. Castration on days 1 and 10 suppressed play-fighting. The behaviours remained suppressed in rats castrated on day 1 and injected with testosterone propionate, but testosterone propionate restored play-fighting to near-normal levels until 35 days of age in rats castrated on day 10. Moreover, gonadally intact juvenile males exposed to the androgen antagonist flutamide play-fought less than intact control males, although their social activity increased appreciably after day 35. It is concluded that the juvenile is not experiencing endocrine quiescence. Behavioural and physiological data suggest a reproductive system which is active, although differently from that in the adult. Hypersensitivity to testosterone and surges of gonadotrophin-releasing factors and LH at 35 days of age may be the events responsible for changes in play-fighting resulting from manipulations of gonadal steroids in juvenile rats.

J. Endocr. (1986) 110, 533–537
RNA synthesis in Leydig cells during sexual maturation in the rat: effect of LH
Authors: Valladares L. E. , Ronco A. M. , Pino A. M.
Published: December 2008

The trophic action of LH on Leydig cells involves the triggering of a number of cellular events including changes in protein synthesis. This latter change has led a number of workers to postulate an effect of LH on RNA synthesis. A direct action of LH on RNA synthesis, however, has been difficult to assess.

The aim of the present work was to analyse the effect of LH on RNA synthesis in vitro during sexual development. Studies were performed using purified Leydig cells from rats of 20, 30, 40, 50, 60 and 90 days of age. The results obtained show that basal uridine incorporation into RNA increases in an age-dependent manner in rats from 20 to 60 days of age and then remains unchanged until 90 days of age. A stimulatory effect of LH on RNA synthesis was clearly demonstrated only in the youngest rats (20 and 30 days old). In order to differentiate the effect of LH on different RNA populations, the RNA synthesized by immature and mature rats was analysed using a poly(U)-Sepharose column. In 20-day-old rats, LH stimulated both unbound and poly(A) RNA, although a more marked effect was clearly demonstrated on the latter. On the other hand, LH had an identical effect on both unbound and poly(A) RNA obtained from Leydig cells of 60-day-old rats.

This stimulatory effect of LH on RNA synthesis in Leydig cells from immature rats seemed specific, since effectors which act on interstitial cells, such as LH-releasing hormone, [Arg8]-vasopressin and FSH (which may act on macrophages) did not modify RNA synthesis. It is concluded that LH stimulates RNA synthesis in rat Leydig cells and that this effect is expressed differentially according to sexual maturity.

J. Endocr. (1986) 110, 551–556
[3H]9-desglycinamide,8-arginine vasopressin: metabolism and in-vivo fate
Authors: Verhoef J. , van den Wildenberg H. M. , van Nispen J. W.
Published: December 2008

Half-lives based on the disappearance of [3H]9-desglycinamide,8-arginine vasopressin ([3H]DGAVP) following in-vitro incubation in plasma were 1·7 h (dog), 5·8 h (rat) and > 12 h (man). For all three species, and particularly dogs, biotransformation of the peptide in plasma occurred predominantly through carboxypeptidase activities, leading to the accumulation of AVP-(1–7). Disappearance of [3H]DGAVP from rat blood after a single i.v. injection followed a biphasic decay with half-lives of 2·2 ± 0·8 (s.d.) min (distribution phase) and 14·4±1·2 min (elimination phase). The central and peripheral volumes of distribution were high and of the same order of magnitude, being 0·21 and 0·25 litres/kg respectively. Blood clearance values ranged from 36 to 45 ml/min per kg. In addition to [3H]AVP-(1–7), [3H]tyrosine was also found to be a major radioactive metabolite in blood. Compared with i.v. dosing, the s.c. route of administration for [3H]DGAVP resulted in longer-lasting peptide levels in blood which persisted for up to 4–5 h after injection. Maximal concentrations were reached at 7·5 min, whereafter they declined bi-exponentially with terminal half-lives of 31·1±8·7 min. The mean bioavailability for DGAVP was almost 100%, demonstrating virtually complete absorption from the s.c. injection site.

J. Endocr. (1986) 110, 557–562
Effects of various inhibitors of phenylethanolamine N-methyltransferase on pulsatile release of LH in ovariectomized rats
Authors: Coen C. W. , Gallo R. V.
Published: December 2008

This study was undertaken to investigate whether hypothalamic adrenaline is involved in pulsatile LH release in rats. Various inhibitors of phenylethanolamine N-methyltransferase (PNMT), the enzyme which catalyses the conversion of noradrenaline to adrenaline, were administered to freely moving ovariectomized rats bearing an atrial cannula.

Blood samples were taken continuously from 09.00 to 11.00 h and from 14.30 to 17.00 h. The drugs were administered either at 11.00 h only or at both 11.00 and 14.00 h. The various treatments with the vehicle or an inhibitor of peripheral PNMT, SKF 29661, produced no decrease in any parameter of pulsatile LH release. A single injection of one of the central PNMT inhibitors, SKF 64139 or LY 134046, at 11.00 h had no effect on LH release, but when given at both times the drugs suppressed the mean LH level, pulse frequency and amplitude.

The effect of these drugs on the level of dopamine, noradrenaline and adrenaline in the hypothalamus (including preoptic area) was assessed. There was no effect on the concentration of the catecholamines after SKF 29661. None of the treatments with SKF 64139 or LY 134046 resulted in a change in the level of dopamine or noradrenaline; the double dose did, however, produce a significantly greater depletion of adrenaline than that which was achieved with the single injection.

These results suggest that the maintenance of normal LH pulses is dependent upon the presence of a sufficient level of hypothalamic adrenaline. The presence of at least 41% of the control level of hypothalamic adrenaline was compatible with the maintenance of LH pulses, but 30% or less of that level was insufficient for their normal occurrence. The effects of LY 134046 are particularly significant since this drug, unlike some of the other PNMT inhibitors, lacks α-adrenergic antagonist properties.

J. Endocr. (1986) 111, 51–59
Parathyroid hormone stimulation of the Na+/K+ pump in rat clonal osteosarcoma cells
Authors: De Luise M. , Harker M.
Published: December 2008

A clonal line of osteoblastic cells from a rat osteogenic sarcoma (UMR 106–06), known to possess parathyroid hormone (PTH)-responsive adenylate cyclase, has been shown to increase its rate of K+ uptake mediated by a Na+/K+ pump after exposure to the hormone. The increase in pump activity was not associated with significant changes in K+ efflux or Na+ influx and would therefore be expected to alter intracellular levels of both Na+ and K+. The maximal (75%) increase in pump activity was noted at a PTH concentration of 100 μg/l and half-maximal stimulation at 1·9 μg/l. The effect appeared to be independent of the adenylate cyclase system, since a synthetic peptide antagonist of PTH activation of adenylate cyclase failed to prevent stimulation of the Na+/K+ pump. Similarly, prostaglandin E2, an alternative agonist of adenylate cyclase in these cells, had no effect on the Na+/K+ pump. This novel action of PTH on monovalent cation transport in osteoblast-like cells should provide a clearer insight into the mechanisms of hormone-induced bone resorption.

J. Endocr. (1986) 111, 61–66
Mechanism of restoration of ACTH release in rats with long-term lesions of the paraventricular nuclei
Authors: Dohanics J. , Kapócs G. , Janáky T. , Kiss J. Z. , Rappay G. , Lászlo F. A. , Makara G. B.
Published: December 2008

The effects of lesions in the paraventricular nucleus (PVN) on the adrenocortical response to ether stress were investigated in neurohypophysectomized and intact rats. During the first 4 days after placement of lesions in the PVN, the corticosterone response to ether stress was almost completely inhibited. It then gradually increased and, within 4–6 weeks of surgery, was restored to about 60% of that in sham-operated rats.

Basal plasma concentrations of corticosterone were low in rats after placement of lesions in the PVN and/or after neurointermediate lobectomy (NILX). Corticosterone responses to ether stress were similar in groups submitted to PVN lesions and/or NILX, and lower than those in the appropriate sham-operated groups. In all lesioned groups, plasma ACTH concentrations after a combination of stressors (ether plus laparotomy) were also lower than those in the sham-operated groups.

Six weeks after lesioning of the PVN, immunoreactive rat corticotrophin-releasing factor-41 (rCRF-41) concentrations in stalk-median eminence (SME) extract fell to about 5% of that in sham-operated rats, while immunoreactive arginine vasopressin (AVP) concentrations did not change. Immunohistochemistry revealed a substantial decrease in rCRF-41 immunostaining of the median eminence 6 weeks after lesioning of the PVN, though randomly located clusters of stained terminals were still seen in the whole rostro-caudal extent of the median eminence. A mixture containing synthetic rCRF-41 and AVP, in proportions similar to those in SME extracts from sham-operated rats, caused significantly less release of ACTH from anterior pituitary cell cultures than did SME extracts from sham-operated rats. Extracts of SME from PVN-lesioned rats released as much ACTH as a mixture containing synthetic rCRF-41 and AVP in proportions similar to those in the SME extracts from PVN-lesioned rats. Extracts of SME from either PVN-lesioned or sham-operated rats did not cause a significant increase in the amount of ACTH released when preincubated with antisera to both rCRF-41 and AVP.

It is suggested that (1) the restoration of the adrenocortical reponse to ether stress, evident within a few days of placement of lesions in the PVN, occurs independently of neurohypophysial function; (2) the full corticosterone and ACTH response to ether or ether plus laparotomy stress requires not only an intact PVN but also an intact neurointermediate lobe; (3) SME extracts from sham-operated rats contain a factor(s) with the ability to potentiate the ACTHreleasing effect of rCRF-41 and AVP; and (4) the ACTH-releasing activity of SME extract obtained from rats with long-term PVN lesions is probably due to its remaininJ content of rCRF-41 and AVP.

J. Endocr. (1986) 111, 75–82
Effects of histamine H1- and H2-receptor antagonists on thyrotrophin secretion in the rat
Authors: Ulloa E. R. , Zaninovich A. A.
Published: December 2008

The effects of histamine H1- and H2-receptor antagonists on the pituitary-thyroid axis were studied in normal and thyroxine (T4)-treated rats. Acute administration (120 min before the test) of the H2 antagonist cimetidine induced a significant (P<0·01) increase in the TSH response to TRH, whereas treatment with histamine (30 min before the test) or with the H1-receptor blocker diphenhydramine (120 min before the test) was without effect. Treatment with cimetidine or ranitidine (another H2-receptor antagonist) for 5 days induced a marked decrease in basal plasma TSH concentrations (P<0·01), with no changes in pituitary concentrations of TSH. Plasma prolactin concentrations were similarly decreased by cimetidine (P<0·01), though not by ranitidine. Neither antihistaminic altered pituitary prolactin concentrations. Despite decreasing basal concentrations of plasma TSH, cimetidine augmented the response to TRH above baseline values (P<0·01) in control rats as well as in animals with T4-induced suppression of plasma TSH. Administration of cimetidine or ranitidine for 5 days was followed by a reduced concentration of plasma T4 and tri-iodothyronine (T3) (P<0·05 and P<0·01 respectively), perhaps as a result of the declining plasma TSH levels. These results provide the first evidence for the reduction of plasma TSH concentrations by H2-receptor blockers, and may indicate that histamine can physiologically regulate TSH and prolactin secretion through H2 receptors in the anterior pituitary. The results, however, do not disprove a central action of histamine, since the decreased plasma TSH concentrations in the presence of low plasma T4 and T3 concentrations, and also the decrease in plasma prolactin concentrations induced by cimetidine, suggest reduced hypothalamic stimulation.

J. Endocr. (1986) 111, 175–180
Metabolic effects of a biphasic oral contraceptive preparation containing ethinyloestradiol and desogestrel on serum lipoproteins and apolipoproteins
Authors: Voorhoof L. , Rosseneu M. , Caster H. , De Keersgieter W.
Published: December 2008

The effect of the administration of a biphasic oral contraceptive containing ethinyloestradiol and desogestrel on the distribution and composition of serum lipoproteins was studied in a group of 17 healthy female volunteers. The women were treated for a period of 6 months and compared with a control group of ten untreated volunteers.

The serum lipoproteins were fractionated by density gradient ultracentrifugation into very low density lipoproteins (VLDL), low density lipoproteins (LDL), and into the high density lipoprotein (HDL) subfractions 2 and 3 (HDL2, HDL3). Lipids and apolipoproteins were assayed in the various fractions. No modification of either the lipid or apolipoprotein concentrations was observed in the control group. In the treated group, sex hormone-binding globulin (SHBG) and cortisol-binding globulin (CBG), and the serum content of cholesterol, triglycerides, HDL-cholesterol, apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) increased significantly after 3 and 6 months. The cholesterol and apolipoprotein B (apo B) content of VLDL increased significantly after 3 and 6 months, but remained unchanged in LDL.

High density lipoprotein subfraction 2 (HDL2)-cholesterol was significantly increased after 3 and 6 months but apo A-I only after 6 months. Since apo A-II did not change, the apo A-I/A-II ratio increased significantly after 6 months of treatment. In the HDL3 fraction, the apo A-I increase was significant after 3 and 6 months, while the increase of apo A-II was significant after 6 months. The apo A-I/A-II ratio remained constant.

The major effects with this particular preparation were observed on the oestrogen-sensitive variables and especially on apo A–I synthesis. The progestational compound desogestrel does not seem to affect significantly the lipoprotein profile changes induced by the oestrogenic compound.

J. Endocr. (1986) 111, 191–196
A sex difference in endogenous opioid regulation of the posterior pituitary response to stress in the rat
Authors: Carter D. A. , Williams T. D. M. , Lightman S. L.
Published: December 2008

The influence of endogenous opioids on the posterior pituitary response to stress was investigated by measuring plasma hormone levels in immobilized male and female rats following either acute naloxone treatment or prolonged morphine administration. Naloxone significantly potentiated the oxytocin and arginine vasopressin (AVP) response to immobilization, but in female rats only. The responses of morphine-treated male rats showed differences compared with vehicle-treated controls, although chronic morphine treatment did not reliably alter the oxytocin or AVP responses to immobilization in males or females.

In a further experiment to investigate the role of gonadal hormones in determining the sex difference in responsiveness to naloxone, it was found that acute naloxone treatment significantly potentiated the posterior pituitary response to stress in castrated male rats.

These results extend previous studies showing a sex difference in stress-induced secretion of posterior pituitary hormones, providing evidence of a sexual dimorphism in the endogenous opioid regulation of this response which is partly determined by circulating gonadal hormones.

J. Endocr. (1986) 111, 239–244
Effect of growth hormone-secreting tumours on skeletal muscle cellularity in the rat
Authors: McCusker R. H. , Campion D. R.
Published: December 2008

Tumours secreting GH (GH1) or GH plus prolactin (GH3) were induced in young (1-week-old) and mature (17-week-old) female Wistar–Furth rats. Young animals were killed at 11 weeks and mature rats at 30 weeks of age. Induction of tumours increased serum GH concentrations and body and soleus muscle weights when compared with those of control rats. The soleus and extensor digitorum longus (EDL) muscles were examined in transverse section by electron microscopy. The percentages of myofibres with myonuclei and with satellite cell nuclei present in both the soleus and EDL muscles were generally greater in young rats with tumours than in young control rats. The percentage of myofibres in the EDL muscle with myonuclei present was higher in mature rats with GH1 tumours compared with age-matched controls. The presence of tumours did not affect the number of fibres in the soleus muscle of either young or mature rats. It was concluded that increased GH concentrations increased muscle weight by increasing the DNA content of myofibres and by myofibre hypertrophy. The rate of proliferation of satellite cells apparently exceeded the rate of incorporation of daughter nuclei into the fibres of the young tumourbearing rats when compared with that of young controls. Thus, the factors regulating satellite cell proliferation and nuclear incorporation into the myofibre do not appear to be directly coupled.

J. Endocr. (1986) 111, 279–285
The relationship between perfusion medium flow rate and steroid secretion in the isolated perfused rat adrenal gland in situ
Authors: Hinson J. P. , Vinson G. P. , Whitehouse B. J.
Published: December 2008

Using the in-situ, isolated, perfused rat adrenal preparation, we have investigated the effects of changes in the rate of perfusate flow through the gland, brought about both mechanically and by the use of vasoactive agents, in the absence of known adrenocortical stimulants. Adenosine caused a significant increase in the rate of perfusate flow through the adrenal, with a concomitant rise in corticosterone, but not aldosterone, secretion. Adrenaline, on the other hand, caused a decrease in the rate of perfusate flow through the gland, accompanied by a decrease in the rate of steroid secretion. Futhermore, increases in the rate of delivery of perfusate to the gland, brought about by increasing the peristaltic pump rate, caused a large increase in corticosterone secretion, although aldosterone was unaffected. Neither adenosine nor a mechanically increased rate of perfusate delivery increased steroid secretion by collagenase-dispersed rat adrenocortical cells superfused on a Sephadex column. These results suggest the existence of hitherto unsuspected intraglandular mechanisms for the control of steroid secretion.

J. Endocr. (1986) 111, 391–396
Prostaglandin F2α-induced functional luteolysis: interactions of LH, prostaglandin F2α and forskolin in cyclic AMP and progesterone synthesis in isolated rat luteal cells
Authors: Kenny N. , Robinson J.
Published: December 2008

The acute antigonadotrophic action of prostaglandin F2α (PGF2α) was examined in dispersed luteal cell preparations from immature superluteinized rat ovaries. Cell suspensions prepared by collagenase digestion and purification over a Percoll density gradient were incubated for 1 h in Eagle's minimum essential medium in the presence and/or absence of LH, PGF2α, N6,O2′-dibutyryladenosine 3′,5′-cyclic monophosphate (dbcAMP) and forskolin. Medium was assayed for total progesterone and adenosine 3′,5′-cyclic monophosphate (cAMP). Luteal cell preparations showed typical steroidogenic (progesterone) responses to LH, mimicked by both dbcAMP and forskolin. Whilst the threshold LH dose to increase cAMP synthesis was greater than that for progesterone (100 μg/l compared with 1 μg/l), 24 μmol forskolin/l was the threshold dose for both cAMP and progesterone responses. Furthermore, combined doses of LH and forskolin synergistically raised cAMP yet produced less than additive increases in progesterone. Similarly, combinations of dbcAMP plus forskolin produced less than additive progesterone increases. These data suggest that forskolin may not act as a simple mimic of LH.

Prostaglandin F2α dose-dependently inhibited forskolin-induced cAMP and progesterone synthesis and also inhibited progesterone synthesis induced by dbcAMP. These data suggest that the antigonadotrophic effect of PGF2α has more than one locus of action, i.e. it both inhibits an adenylate cyclase event associated with cAMP generation and blunts the cellular response to cAMP. The present uncertainty over the exact locus of forskolin's action within the adenylate cyclase complex limits further delineation of the inhibitory action of PGF2α on LH-responsive adenylate cyclase.

J. Endocr. (1986) 111, 415–423
Kinetic measurement of the urinary production rate of cortisol in male piglets: is the prerequisite 'collection until all label has disappeared' necessary?
Authors: Kraan G. P. B. , Chapman T. E. , Drayer N. M. , Colenbrander B. , Buwalda G.
Published: December 2008

Urinary cortisol production rate (CPR) was calculated by two different methods in five male piglets (about 3 kg bodyweight) injected i.v. with 40–120 kBq tritiated cortisol ([3H]F). After administration of [3H]F, urine was obtained from four consecutive collections for the following 2 days, during which 80–100% of the label was recovered. Total radioactivity in the urine was measured and used to calculate the total rate constant of 0·115 ± 0·011 h−1 and, from this, the mean biological half-life (t½) of 6·0±0·6 h (s.d.; n = 4). It was found that the mass ratio of the two principal urinary cortisol metabolites tetrahydrocortisone (THE) and tetrahydrocortisol (THF) was strikingly less than 1·0 (0·4±0·1; n= 14), which is the reverse of that observed in older pigs, neonatal infants and man. To calculate CPR conventionally, the cumulative specific activities of THE and THF were calculated for the 2-day period of urine collection. The apparent mean CPR values on the basis of THE and THF were calculated as 11·5±1·6 (n = 5) and 12·8 ± 3·3 (n = 5) μmol/day respectively, and 12·1 ± 1·4 (n = 5) μmol/day for the average of THE and THF.

The second method for calculating CPR consisted of determining the masses of THE and THF (μmol) per fraction of dose (m/fd) (fd refers to the ratio of radioactivity in the metabolite and dose) at different times after administration of [3H]F. The calculated m/fd values, which are synonymous with the dose divided by the specific activities of the metabolites, and the different times of urine collection were analysed by linear regression. The resulting slope is equal to the CPR. The CPR derived by this method for the average of THE and THF, 10·1±0·91 μmol/ day was significantly (P<0·014) lower than that derived conventionally, 12·1 ± 1·40 μmol/day.

This second method may be used when CPR is determined in neonatal infants by means of non-radioactive, deuterated or 13C-enriched cortisol, where the extent of negative feedback by the relatively high dose of exogenous steroid on cortisol secretion must be kept as low as possible. This method also allows urine collections to be used at times when the tracer is still being excreted.

J. Endocr. (1986) 111, 439–448
Multiple injections of LH-releasing hormone into hypogonadal (hpg) mice induce the appearance of two morphologically distinct populations of gonadotrophs
Authors: Lewis C. E. , Megson A. , Morris J. F. , Charlton H. M.
Published: December 2008

We have investigated the effects of multiple 2-hourly injections of LH-releasing hormone (LHRH) on the number and size of the gonadotrophs and gonadotroph secretory granules, and the lipid content of gonadotrophs in the pituitary glands of intact and gonadectomized male and female hypogonadal (hpg) mice. Gonadotrophs were identified by immunocytochemistry for LHβ, and the size and secretory status of the gonadotrophs were assessed by quantitative ultrastructural analysis of immunoidentified gonadotrophs. The administration of 60 ng LHRH by subcutaneous injection every 2 h for 15 days resulted in an increase in the number, size and granule content of LHβ-immunoidentified gonadotrophs of hpg mice to values found in normal adult mice. Large lipid droplets accumulated in 30–40% of the gonadotrophs in both male and female LHRH-treated hpg mice. Although lipid-containing gonadotrophs were larger than lipid-free cells in all LHRH-treated groups irrespective of the presence or absence of gonads, a marked difference in the number, position within the cell, and size of the secretory granules between the lipid-containing and lipid-free cells was found only in the pituitary glands of intact LHRH-treated hpg females.

These results demonstrate: (a) that the effects of multiple injections of LHRH on the morphology of the gonadotrophs of hpg mice is not dependent on the presence of functioning gonads, although ovarian factors are required for the full development of morphological, and hence possibly functional, heterogeneity in the gonadotroph population in female animals, and (b) that, although multiple injections of LHRH in hpg mice are more effective than single daily injections of LHRH in stimulating pituitary-gonadal function, there is no obvious difference in the morphologically recognizable effects that these two modes of administration have on the pituitary gonadotrophs.

J. Endocr. (1986) 111, 483–493
Coronary artery ligation and reperfusion in rabbits made diabetic with alloxan
Authors: Bhimji S. , Godin D. V. , McNeill J. H.
Published: December 2008

The biochemical and functional changes associated with ligation (40 min) of the left circumflex coronary artery and subsequent reperfusion (60 min) in the rabbit made diabetic with alloxan were studied and compared with those of control animals. Measurement of haemodynamic parameters revealed that both left ventricular pressure and mean arterial pressure were significantly (P < 0·05) decreased after ligation and reperfusion in the diabetic animals compared with controls. Analysis of subcellular organelle enzyme markers from the ischaemic tissue revealed that sarcolemmal Na+,K+-ATPase, mitochondrial ATPase and sarcoplasmic reticulum ATPase activities were decreased after ligation to the same extent in the diabetic and control animals. However, upon reperfusion, the recovery of mitochondrial ATPase activity was significantly (P < 0·05) less in the diabetic animals than in the controls. Ion measurements revealed a significant (P < 0·05) depletion of Mg in diabetic hearts before ligation, and this was augmented during reperfusion. In contrast, a significantly (P < 0·05) higher calcium accumulation was observed upon reperfusion in the hearts of diabetic animals. Similarly, both tissue ATP levels and the ability of the mitochondria to generate ATP were depressed to a greater degree in the diabetic animals. Our results indicate, therefore, a greater susceptibility of the diabetic myocardium to ischaemic/reperfusion injury which in the clinical situation would exacerbate the problems associated with atherosclerosis and possibly contribute to the high mortality from cardiovascular complications in diabetic patients.

J. Endocr. (1987) 112, 43–49
Effect of pulsatile infusion of gonadotrophin-releasing hormone on plasma oestradiol-17β concentrations and follicular development during naturally and artificially maintained high levels of plasma progesterone in heifers
Authors: Glencross R. G.
Published: December 2008

To stimulate a follicular-phase pattern of pulsatile LH release, gonadotrophin-releasing hormone (GnRH; 5 μg) was infused (i.v.) hourly into heifers for periods of 5–11 days during the luteal phase of the oestrous cycle, and also when plasma progesterone levels were increased artificially by means of a progesterone-releasing intravaginal device.

Plasma oestradiol-17β concentrations increased from basal (EEE 2·5 pmol/l) to preovulatory peak levels (20–30 pmol/l) during the first 3 days of GnRH treatment. They were maintained at these values before returning to basal levels within 24 h of cessation of infusion. This response occurred regardless of the source of progesterone (endogenous or administered). Follicular development was observed by ovarian palpation (per rectum) in some heifers at the time of maximum secretion of oestradiol-17β. There was no detectable cervical mucus secretion or oestrous behaviour during these periods of high oestradiol-17β levels and ovulation did not occur. Treatment with GnRH did not affect plasma progesterone concentrations or oestrous cycle length.

The study shows that oestradiol-17β secretion and follicular development (and the accompanying oestrus and ovulation) are suppressed during the luteal phase of the cycle by high concentrations of plasma progesterone, and provides strong indirect evidence that such inhibition is associated with a reduction in the pulse frequency of LH release.

J. Endocr. (1987) 112, 77–85
Changes in plasma concentrations of LH, FSH and prolactin in ewes receiving melatonin and short-photoperiod treatments to induce early onset of breeding activity
Authors: Poulton A. L. , English J. , Symons A. M. , Arendt J.
Published: December 2008

Breeding activity was similarly advanced in ewes given continuous (s.c. implant) or timed (oral dose at 15.30 h) melatonin treatments or subjected to a short (8 h light: 16 h darkness) artificial photoperiod. Treatments commenced in mid-June and were terminated in mid-November. Weekly and serial blood samples were collected before and after treatments commenced, to ascertain the effects on plasma prolactin, LH and FSH concentrations. In addition, serial blood samples were collected for 24 h plasma prolactin and melatonin estimations before and after cessation of the treatments.

Plasma prolactin levels were significantly reduced immediately following the start of the melatonin (implant and oral) and short-photoperiod treatments but 'rebounded' to levels greater than control values. The normal seasonal (spring) rise in plasma prolactin was noted in the following year. Before the onset of breeding activity, mean plasma LH and FSH concentrations and LH pulse frequency did not change following any of the treatments. The 24-h plasma melatonin profile accurately reflected the various applied treatments but had re-entrained to the prevailing (natural) photoperiod 1 week after termination of the treatments. There were no significant group differences in 24-h plasma prolactin levels 1 week before or 1 and 11 weeks after the treatments had ceased.

Such treatments, although successfully advancing the onset of breeding activity and modifying the seasonal plasma prolactin rhythm, were not manifested through any apparent change in peripheral LH or FSH.

J. Endocr. (1987) 112, 103–111
Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate
Authors: Tilley W. D. , Horsfall D. J. , McGee M. A. , Alderman J. E. , Marshall V. R.
Published: December 2008

Cytosolic oestrogen receptor levels in guinea-pig prostate tissue were found to decrease with increasing age, irrespective of whether the binding was expressed relative to cytosolic protein or cellular DNA. This decrease in oestrogen receptor levels was also observed using enriched fibromuscular stromal tissue prepared by mechanical fractionation of the prostate. The most pronounced change in cytosolic oestrogen receptor levels (from 133 to 35 fmol/mg protein) occurred at the onset of puberty. The pubertal decrease in receptor levels could not be attributed to an increase in the level of proteolytic activity in prostatic cytosol fractions derived from mature animals, a change in the affinity of the receptor for oestradiol or an increase in oestrogen receptor levels in salt-extracted nuclear fractions. Administration of tamoxifen (1 mg/day) to intact guinea-pigs throughout the transpubertal growth phase did not influence the age-related decrease in cytosolic and nuclear oestrogen receptor levels. In contrast, the decrease in oestrogen receptor levels was prevented by castration. Administration of dihydrotestosterone (DHT; 1 mg/day) to intact prepubertal animals for 4 days before study resulted in diminished cytosolic oestrogen receptor levels; this effect of DHT was blocked by the non-steroidal antiandrogen flutamide (2 mg/day). Furthermore, elimination of testicular hormones by castration during the late-pubertal growth phase resulted in a greater than twofold increase in prostatic oestrogen receptor levels. Collectively, these observations suggest an age-related decrease in oestrogen receptor levels in the guinea-pig prostate which, in part, may be due to increased testicular function at puberty.

J. Endocr. (1987) 112, 139–144
Intranuclear distribution of androgen receptors in human prostate carcinoma
Authors: Kyprianou N. , Gingell J. C. , Davies P.
Published: December 2008

Androgen receptors in nuclei from human prostate carcinomas were characterized on the basis of their solubilization by, or resistance to, micrococcal nuclease. By this means, androgen receptors were assigned to three nuclear categories: those associated with nuclease-resistant structures, those associated with chromatin and those apparently uncommitted by association with either of these. Prostate carcinoma nuclei contained high concentrations (57–82% of total nuclear content) of nuclease-resistant androgen receptors. This was a different pattern from that observed previously for benign hypertrophic prostate epithelial nuclei which contained a variable high proportion of uncommitted androgen receptors. The differences could not be attributed to differential losses to cytosol, or to loss of functionality, as determined in vitro. The differences in distribution could reflect different responses of diseased cells to androgens, or the intervention of other factors more relevant to the disease process.

J. Endocr. (1987) 112, 161–169
Effect of an inhibitor of 3β-hydroxysteroid dehydrogenase on progesterone concentrations and embryo survival in sheep
Authors: Ashworth C. J. , Wilmut I. , Springbett A. J. , Webb R.
Published: December 2008

The effect of an inhibitor of 3β-hydroxysteroid dehydrogenase on peripheral progesterone concentration during the luteal phase of the oestrous cycle and on embryo survival was determined in sheep. Following administration of 10, 50, 100 or 250 mg epostane (4,5-epoxy-17-hydroxy-4,17,dimethyl-3-oxo-androstane-2-carbonitrile) progesterone concentrations were significantly lower than control levels 4 h after injection, from 2·5 to 22 h, 1·5 to 24 h and 1 to 24 h after injection respectively. There appeared to be no effect on peripheral oestradiol concentrations. Adrenal progesterone production was small and not influenced by epostane treatment.

Epostane was administered on day 9 of the oestrous cycle to cause a reduction in progesterone concentrations for approximately 12-18 h on day 9 only (group 1, 250 mg epostane on day 9), or a series of such reductions on 3 consecutive days (group 2, 50 mg epostane on days 9, 10 and 11) or a continuous reduction for 3 days (group 3, 250 mg epostane on days 9, 10 and 11). The proportion of ewes that were pregnant was significantly (P<0·05) lower in ewes treated to give a continuously low progesterone concentration for 3 days than in either controls or ewes in which progesterone concentration was reduced for less than 24 h (in controls and groups 1, 2 and 3 the proportion was 85, 92, 54 and 18% of ewes treated respectively). Embryo survival was not affected by administration of 250 mg epostane on days 9, 10 and 11 if luteal phase levels of progesterone were maintained by insertion of a silicone elastomer implant of the steroid. The proportion of embryos surviving was 72% in controls compared with 78% in the treated animals.

J. Endocr. (1987) 112, 205–213
Effects of hyperprolactinaemia on male sexual behaviour in the golden hamster and mouse
Authors: Shrenker P. , Bartke A.
Published: December 2008

In the male rat, hyperprolactinaemia is associated with significant reductions in plasma LH and FSH levels and in several measures of copulatory behaviour. In contrast to this situation, experimental induction of hyperprolactinaemia in male mice and hamsters is associated with an increase in plasma gonadotrophin levels. It was therefore of interest to determine the effects of hyperprolactinaemia on the copulatory behaviour of these animals. Hyperprolactinaemia was induced by transplantation of pituitaries from adult females and sexual behaviour was tested in the presence of ovariectomized, oestrogen- and progesterone-treated females. Because hyperprolactinaemia increases plasma testosterone levels in intact male hamsters, the animals were castrated and implanted with testosterone-filled silicone elastomer capsules before induction of hyperprolactinaemia. In mice of two inbred strains, DBA/2J and C57BL/6Bg, hyperprolactinaemia appeared to stimulate male sexual behaviour as shown by a significant increase in the proportion of animals mating (C57BL/6) and a significant decrease in mount (DBA/2J) and intromission (C57BL/6Bg and DBA/2J) latencies. Similarly, hyperprolactinaemia did not suppress male copulatory behaviour in the hamster. In contrast, in two experiments in which the animals were tested three times for sexual behaviour, mount or intromission latencies were significantly reduced in pituitary-grafted, as compared with sham-operated males, in the first of the tests. Thus, in the mouse and the golden hamster, experimentally induced chronic hyperprolactinaemia stimulates both gonadotrophin release and male copulatory behaviour. These observations, together with the association of suppressive effects of hyperprolactinaemia on plasma LH and FSH levels and on sexual behaviour in the male rat, suggest the possible existence of a common mechanism underlying both endocrine and behavioural effects of hyperprolactinaemia. We suggest that the suspected effects of hyperprolactinaemia on the release of endogenous LHRH in the hypothalamus may represent such a mechanism.

J. Endocr. (1987) 112, 221–228