bluuebunny/crossref_metadata_2025 huggingface dataset:
UNIT ACTIVITY IN THE PARAVENTRICULAR NUCLEUS OF FEMALE RATS AT DIFFERENT STAGES OF THE REPRODUCTIVE CYCLE AND AFTER OVARIECTOMY, WITH OR WITHOUT OESTROGEN OR PROGESTERONE TREATMENT
Authors: NEGORO H. , VISESSUWAN S. , HOLLAND R. C.
Published: December 2008

Spontaneous firing rates were determined from extracellular recordings made from 878 antidromically identified units in the paraventricular nucleus (PVN) during the reproductive cycle of the female rat and in analytical experiments. In the latter, rats were ovariectomized and subsequently received either no treatment or oestrogen and/or progesterone. Among rats at metoestrus, dioestrus, mid-pregnancy and in ovariectomized progesterone-treated groups there was no significant difference in the firing rates. However, they were significantly lower than the rates recorded during pro-oestrus, oestrus, full-term pregnancy, the day of parturition, during lactation and in ovariectomized, oestrogen-treated rats. In spayed rats the mean firing rate was significantly lower than at pro-oestrus, oestrus, fullterm pregnancy, the 24 h period after parturition, during lactation and after oestrogen treatment. When progesterone was given subcutaneously to oestrogenized rats, the PVN activity, increased by oestrogen, was significantly depressed 4 h after administration. By 8 h the firing rate had completely recovered.

The frequency distribution of the firing rates in pro-oestrus and oestrus showed an approximately normal distribution while those in metoestrus and dioestrus and mid-pregnancy had a Poisson distribution. At full term there were two peaks: one in the range of 3–5 spikes/s and the other less than one spike/s. The distribution was approximately normal on the day of parturition and subsequently the pattern became irregular. In ovariectomized rats and those treated with progesterone it was of a Poisson type while there was a distinct shift to higher frequencies after oestrogen treatment.

The mean absolute refractory period, measured for each unit, varied and appears to be dependent on hormonal conditions. It was short in oestrus and long in dioestrus and mid-pregnancy. Oestrogen treatment significantly shortened the absolute refractory period of ovariectomized rats.
REFLEX ACTIVATION OF PARAVENTRICULAR NUCLEUS UNITS DURING THE REPRODUCTIVE CYCLE AND IN OVARIECTOMIZED RATS TREATED WITH OESTROGEN OR PROGESTERONE
Authors: NEGORO H. , VISESSUWAN S. , HOLLAND R. C.
Published: December 2008

Three hundred and seventy-seven neurones in the paraventricular nucleus (PVN) were antidromically identified in female rats during various stages of the reproductive cycle and in ovariectomized rats with or without oestrogen or progesterone pretreatment. The units were tested for their responses to vaginal distension and pinching of the foot. Unit responses to vaginal distension varied during the oestrous cycle, pregnancy and lactation. The percentages of PVN units recorded at each stage which increased their firing rate in response to vaginal distension were 64·1% in pro-oestrus, 56·7% in oestrus, 33·3% in metoestrus, 42·4% in dioestrus, 6·9% in mid-pregnancy (day 12) which was significantly lower than in any other stage or condition, 72·0% at full term, 55·5% immediately (<24 h) after parturition and 40·0% during lactation. Furthermore, when tested in mid-pregnancy, there was a period of interruption of spontaneous firing in 13·8% of PVN units during vaginal distension.

The percentage of units which increased their firing rate during vaginal distension in ovariectomized rats was 42·4% and in ovariectomized, oestrogen-treated rats was 69·2% and thus significantly higher. While the percentage in progesterone-treated rats (35·1%) was not significantly different from that in ovariectomized rats, it was significantly lower than in the oestrogen-treated group. In addition, 18·9% of the units had a period of interruption of spontaneous firing in response to vaginal distension constituting the only group besides the mid-pregnancy group in which this was observed.

Pinching the foot also excited PVN unit activity in some cases. It was more frequently evoked by pinching a foot contralateral to the PVN nucleus from which the recording was taken. The response to stimulation of the ipsilateral foot was weaker or absent. The responsiveness of PVN units to pinching varied throughout the reproductive cycle as well as in ovariectomized rats with or without treatment with oestrogen or progesterone. The pattern of variation was dissimilar from that observed after vaginal distension and the magnitude of variation was smaller. Interruption of spontaneous firing was observed in seven different groups.
ESTIMATION OF OESTRONE SULPHATE, OESTRADIOL-17β AND OESTRONE IN PERIPHERAL PLASMA: CONCENTRATIONS DURING THE MENSTRUAL CYCLE AND IN MEN
Authors: HAWKINS R. A. , OAKEY R. E.
Published: December 2008

A method for the determination of oestrone sulphate, oestradiol-17β and oestrone in human peripheral plasma is described, and the accuracy, specificity, precision and sensitivity of each analysis is defined.

Free oestrogens were extracted from plasma with ether. Oestradiol-17β was isolated by chromatography on silica gel. Oestrone, similarly purified, was reduced to oestradiol-17β and rechromatographed. Oestrone sulphate in the residual plasma was solvolysed and the oestrone liberated was isolated and reduced to oestradiol-17β. All three fractions were estimated separately by competitive protein binding with rabbit uterine cytosol. Manipulative losses were assessed from recovery of [3H]oestradiol-17β and [3H]oestrone added to the plasma and of [3H]oestrone sulphate added to the ether extracted plasma.

The concentration of oestrone sulphate in peripheral plasma of six men greatly exceeded that of oestradiol-17β or oestrone. The mean concentrations were respectively, 72, 2·3 and 3·6 ng/100 ml. Analysis of samples collected daily during a menstrual cycle from each of two women also showed that the concentration of oestrone sulphate was much greater than that of oestradiol-17β or oestrone. Changes in the concentrations of all three oestrogens occurred at similar times in the cycle. At mid-cycle, the mean concentrations were: oestrone sulphate, 308 ng/100 ml; oestradiol-17β, 57 ng/100 ml; oestrone, 15 ng/100 ml.
INHIBITION BY DEXAMETHASONE OF ADRENOCORTICOTROPHIN AND CORTISOL RELEASE INDUCED BY INTRAVENOUS INFUSION OF ATP AND DIBUTYRYL CYCLIC AMP IN PIGLETS
Authors: COOK D. B. , GILL G. V. , JACKSON I. M. D. , SMART G. A.
Published: December 2008

The effect of intravenous infusions of ATP and dibutyryl cyclic AMP (DB cyclic AMP) on adrenocorticotrophin (ACTH) and corticosteroid release was investigated in piglets.

A consistent increase of both plasma ACTH and plasma cortisol was observed in response to infusions of 600 mg ATP/h. These responses were abolished by pretreating the animals with dexamethasone. A similar pattern of response was observed with DB cyclic AMP infused intravenously. No response occurred when 100 mg DB cyclic AMP were infused in 1 h, but there was a marked plasma corticosteroid response to an infusion of 600 mg DB cyclic AMP in 1 h. Surprisingly, this response was also abolished by pretreatment with dexamethasone.
SEASONAL VARIATIONS IN BLOOD LUTEINIZING HORMONE AND TESTOSTERONE LEVELS IN RAMS
Authors: KATONGOLE C. B. , NAFTOLIN F. , SHORT R. V.
Published: December 2008

Three adult Suffolk rams were bled at weekly intervals for 14 months, and at hourly intervals for 24 h during the summer (one ram) and autumn (two rams). Luteinizing hormone (LH) was measured by radioimmunoassay, and testosterone by a competitive protein binding assay.

There were episodic bursts of LH secretion during the 24 h period in both the summer and the autumn; the frequency of discharge was lower in the summer, but the amplitude (0·1–8·0 ng/ml) did not appear to change. It was not always possible to detect seasonal changes in LH concentration in single blood samples taken once a week throughout the year.

The blood testosterone levels also showed marked fluctuations throughout the 24 h, and the frequency of the peaks was lower in the summer. But in contrast to LH, the magnitude of the testosterone peaks also changed throughout the year; from January to September the testosterone concentration ranged from 0·5 to 10 ng/ml plasma, whereas from October to December it ranged from 3 to 28 ng/ml. Thus in temperate regions the ram, like the ewe, shows seasonal changes in gonadal endocrine activity, although some degree of spermatogenesis continues throughout the whole year.
STEROIDS OF ADRENAL ORIGIN METABOLIZED BY HUMAN PROSTATIC TISSUE BOTH IN VIVO AND IN VITRO
Authors: HARPER M. E. , PIKE A. , PEELING W. B. , GRIFFITHS K.
Published: December 2008

The pattern of metabolites present in human benign prostatic tissue after infusion of either [7α-3H]testosterone, [7α-3H]androstenedione or [7α-3H]dehydroepiandrosterone (DHA) sulphate 30 min before prostatectomy were investigated. Infusion of [7α-3H]testosterone yielded 5α-dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) as the major metabolite present in the prostatic tissue together with other 5α-androstane compounds. The major radioactively labelled steroids identified in the prostatic tissue after [7α-3H]androstenedione infusion were epiandrosterone and androsterone, and dehydroepiandrosterone after [7α-3H]DHA sulphate infusion, although various other 5α-androstane compounds were also present after both infusions. The proportion and identity of radioactive steroids present in the epithelial and stromal portions of the tissue after in-vivo infusion of [7α-3H]testosterone was investigated. Also the ability of separated epithelial and stromal elements of prostatic tissue to metabolize steriods in vitro was studied. Dehydroepiandrosterone sulphate and DHA metabolism in vitro by minced human prostatic tissue yielded various 5α-androstane compounds in addition to DHA and androstenediol (androst-5-ene-3β,17β-diol).
BLASTOCYST-ENDOMETRIAL CONTACT AND PONTAMINE BLUE REACTION DURING NORMAL IMPLANTATION IN THE RAT
Authors: LJUNGKVIST I. , NILSSON O.
Published: December 2008

Pregnant rats were injected with pontamine blue on the afternoon of day 5 of normal pregnancy to study, by electron microscopy, blastocyst-epithelial contact at implantation sites negative and positive to the dye. Implantation sites negative to the dye contained merely zona-encased blastocysts. Positive sites contained zona-free blastocysts or blastocysts only partly covered by a zona. Remnants of the zona were often observed. At positive sites intimate cell-membrane contacts between blastocyst and uterine epithelium were always noted. The results obtained suggest zona disappearance by uterine lysis and do not contradict the concept that blastocyst—epithelial contact is involved in decidua induction during normal pregnancy.
EFFECTS OF OESTROGEN ANTAGONISTS ON MITOSIS AND [3H]OESTRADIOL BINDING IN THE MOUSE UTERUS
Authors: LEE AUDREY E.
Published: December 2008

Progesterone and megestrol acetate reduced oestrone-stimulated epithelial mitosis in the mouse uterus and increased it in the stroma. Neither progestin reduced the uptake of [3H]oestradiol by the uterus in vivo. Compounds ICI 46,474 and U11,100A were mitogenic in both luminal epithelium and stroma but did not antagonize the epithelial response to oestrone. U11,100A reduced the uptake of [3H]oestradiol by the uterus in a way similar to that shown by unlabelled oestradiol, but there was no evidence that ICI 46,474 competed for oestrogen receptors.
EXTRAHEPATIC AND EXTRARENAL RENIN INACTIVATION IN THE DOG
Authors: FAGARD R. , FOSSION E. , CAMPFORTS M. , AMERY A.
Published: December 2008

It was demonstrated previously that renin disappears quickly from the circulation after nephrectomy in the hepatectomized dog. In the present study the plasma renin concentration (PRC) was measured in the efferent and afferent blood vessels of several vascular beds (pulmonary circulation, splanchnic region, spleen, both inferior limbs and pelvis, head) in the anhepatic and in the anhepatic and anephric dog in order to investigate extrarenal and extrahepatic renin inactivation. However, no significant arteriovenous differences in PRC could be traced. The blood of these dogs kept in vitro at 37 °C in a glass container showed no decline in PRC within 3 h of removal.

Therefore no specific extrahepatic and extrarenal renin-inactivating mechanism was found which could explain the rapid disappearance of renin from the blood in vivo in the anhepatic and anephric dog.
EVIDENCE FOR DUAL CORTICOSTEROID-RECEPTOR MECHANISMS IN THE FEEDBACK CONTROL OF ADRENOCORTICOTROPHIN SECRETION
Authors: JONES M. T. , TIPTAFT ELIZABETH M. , BRUSH F. R. , FERGUSSON D. A. N. , NEAME R. L. B.
Published: December 2008

The influence of several corticosteroids on stress-induced secretion of adrenocorticotrophin was studied. Two periods of inhibition were demonstrated. Fast feedback occurred within minutes with small doses of corticosterone, and was of short duration which was further curtailed as the dose of corticosterone was raised. Delayed feedback occurred after 1 h or later, required larger doses and the duration of inhibition was increased with increased dosage. Corticosterone and cortisol were agonists on both fast and delayed feedback. However, 11-deoxycorticosterone and 11-deoxycortisol were antagonists on fast feedback but agonists on delayed feedback. It is concluded that the two feedback mechanisms have different dynamics and separate receptors.
INHIBITORY EFFECT OF SEROTONIN ON OVULATION IN ADULT RATS
Authors: WILSON CATHERINE A. , McDONALD P. G.
Published: December 2008

Serotonin (5HT, 100 mg/kg) given subcutaneously between 16.00 and 18.00 h on the day of pro-oestrus, at 17.00 h on day 2 of dioestrus and at 13.00 and 17.00 h on day 1 of dioestrus, inhibited ovulation in adult rats. It was ineffective at 13.00 h on the day of pro-oestrus and on day 2 of dioestrus. The anti-ovulatory effect at 17.00 h during pro-oestrus was reversed by pretreatment with 2–4 mg progesterone or 2·5 mg dipyridamole/kg. The effect at 17.00 h on day 2 of dioestrus was reversed by 2 μg oestradiol benzoate. Subcutaneous injection of 5HT antagonized the ovulatory action of exogenous luteinizing hormone and inhibited the passage of 22Na into ovary, uterus and muscle but not the pituitary. Intraventricular administration of 5HT (200 μg/rat) between 13.00 and 18.00 h during pro-oestrus had no effect on ovulation. These results suggest that subcutaneous administration of 5HT does not inhibit ovulation at a central site, but acts as a peripheral vasoconstrictor preventing the passage of hormones to their target organs.
STIMULATION OF DNA SYNTHESIS IN RAT LIVER BY ADRENALECTOMY
Authors: DESSER-WIEST LUCIA
Published: December 2008

The following effects were observed in the liver of male rats in the first few days after adrenalectomy: the rate of thymidine incorporation into DNA was increased three- to fourfold in the 2 days after adrenalectomy. The mitotic index was increased 5·5-fold on the first day and 15-fold on the second day after the operation. The number of tetraploid cells rose from 40 to 68%. While the subsequent administration of cortisol, cortisone or corticosterone to the adrenalectomized animals reduced DNA synthesis to the normal level, testosterone and oestrone were without effect. It is suggested that liver growth is regulated by the concentration of corticosteroids in the blood.
EFFECT OF MELATONIN AND SHORT PHOTOPERIOD ON Δ4-REDUCTASE ACTIVITY IN LIVER AND HYPOTHALAMUS OF THE HAMSTER AND THE RAT
Authors: FREHN J. L. , URRY R. L. , ELLIS L. C.
Published: December 2008

Adult, male hamsters exposed to a photoperiod of 1 h light: 23 h darkness for either 2, 3, 4, 6, 8, or 10 weeks exhibited significantly lower testicular weights than did controls after 3 and 4 weeks of exposure to 14 h light: 10 h darkness. Liver Δ4-reductase activity was significantly decreased by 4 weeks of exposure to the short photoperiod. Exogenous melatonin decreased Δ4-reductase activity when incubated with either hamster liver (at 10−7 and 10−5 mol melatonin/l) or hamster hypothalamus (at 10−6 mol melatonin/l). In contrast, exogenous melatonin stimulated Δ4-reductase activity in preparations of rat liver (at 10−7 and 10−6 mol/l) and rat hypothalamus (at 10−9, 10−8, 10−7, and 10−6 mol/l). The possible role of melatonin in influencing the testosterone: dihydrotestosterone ratio is discussed in relation to possible regulation of gonadotrophin release.
EFFECT OF MAGNESIUM STATUS ON THYROID ACTIVITY AND IODIDE METABOLISM
Authors: HEATON F. W. , HUMPHRAY H. P.
Published: December 2008

The close positive correlation between the magnesium concentration in serum and the activity of the thyroid gland, as indicated by the ratio of (protein-bound 125I): (total serum 125I) 24 h after injection of a tracer dose of [125I]iodide, was investigated in young male rats. Dietary deficiency or loading with magnesium salts had no effect on the concentration of cyclic AMP within the thyroid gland or the release of thyroid hormone from glands incubated in vitro.

Accumulation of radioactive iodide by thyroid glands in vivo was stimulated by magnesium loading and inhibited by magnesium deficiency, but there was no selective effect on the synthesis of iodinated tyrosines or thyronines within the gland. As similar differences in radioactive iodide uptake were observed in other soft tissues, this appears to be part of a general influence of magnesium status on iodide transport, rather than a specific action on the thyroid gland.
TEMPORAL VARIATIONS OF TESTOSTERONE LEVELS IN THE PERIPHERAL BLOOD PLASMA OF MEN
Authors: ROWE P. H. , LINCOLN G. A. , RACEY P. A. , LEHANE J. , STEPHENSON M. J. , SHENTON J. C. , GLOVER T. D.
Published: December 2008

Testosterone was measured in the peripheral blood plasma of normal men by radioimmunoassay. The results were analysed to test for the possible existence of a circadian rhythm, for fluctuations superimposed on any such rhythm, and for day-to-day variations. Unequivocal evidence of a circadian rhythm was found in all but one of the subjects studied and the cycle appeared to be accompanied by a series of fluctuations of lower amplitude lasting for 1–2 h. Samples taken from the same subjects on consecutive days showed marked variation between days, but no regular cyclic pattern. The possible existence of such a cycle is not, however, eliminated. On the basis of all the data obtained a regime is suggested for the collection of blood samples from individuals whose androgenic status is to be assessed.
CALCITONIN AND INTESTINAL CALCIUM ABSORPTION
Authors: SWAMINATHAN R. , KER J. , CARE A. D.
Published: December 2008

The effect of calcitonin (CT) on small intestinal calcium absorption was studied using Thiry—Vella loops in one intact sheep, one intact pig and three parathyroidectomized pigs. Net calcium absorption rate was measured after recirculating through the loop a known volume of a solution containing calcium and polyethylene glycol 4000. Calcitonin was infused intravenously and its effect on the net calcium absorption rate was measured. When relatively high doses of CT (10 mu./min/kg) were infused for up to 45 h, there was an initial rise in net calcium absorption associated with hypocalcaemia, followed by a marked reduction in calcium absorption. When small doses of CT (0·5 mu./min/kg) were infused for 100 h, the increase in the net absorption rate was not observed or was less marked, but there was a significant reduction in net calcium absorption 2 days after the CT infusion was stopped. A reduction in net calcium absorption rate was seen both in intact and parathyroidectomized animals. In one experiment in which the true absorption rate of calcium from lumen to blood was measured using 47Ca, a reduction in unidirectional transfer of calcium from lumen to blood was seen 2 days after the CT infusion was stopped. The possible mechanism of this action of CT and its significance in calcium homeostasis during the ingestion of a high calcium diet is discussed.
EFFECTS OF 17β-HYDROXY-4-ANDROSTEN-19-OL-3-ONE (19-HYDROXYTESTOSTERONE) AND 5α-ANDROSTAN-17β-OL-3-ONE (DIHYDROTESTOSTERONE) ON ASPECTS OF SEXUAL BEHAVIOUR IN CASTRATED MALE RATS
Authors: PARROTT R. F.
Published: December 2008

The ability of 19-hydroxytestosterone propionate (150 μg/day) to maintain sexual behaviour, accessory organ weights and the number of penile spines in experienced adult male rats in the 5 weeks after castration was compared with intact males and castrated animals receiving testosterone propionate (75 μg/day) or oil treatment. In a second experiment a group of male rats receiving dihydrotestosterone propionate (150 μg/day) was also included. 19-Hydroxytestosterone did not maintain ejaculatory performance but animals that ejaculated had refractory periods similar to those in intact and testosterone-treated groups. Dihydrotestosterone, however, slowed the rate of decline of ejaculatory performance but the refractory periods were comparable to those in castrated controls. The former action of dihydrotestosterone was attributed to its stimulatory effect on peripheral structures, especially the penile spines. 19-Hydroxytestosterone was shown to have no peripheral effect at doses up to 1800 μg every other day. The results are discussed in terms of a theory of testosterone action involving aromatization in the brain and 5α-reduction peripherally.
POSSIBLE INVOLVEMENT OF CYCLIC AMP IN REGULATION OF MASCULINE SEXUAL BEHAVIOUR BY TESTOSTERONE
Authors: CHRISTENSEN L. W. , CLEMENS L. G.
Published: December 2008

Experiments were carried out to assess the possible involvement of cyclic AMP in the regulation of masculine sexual behaviour by testosterone in the laboratory rat. Doses of testosterone propionate which were ineffective in maintaining or inducing male sexual behaviour were potentiated by concurrent administration of theophylline. Since removal of the adrenal glands had no effect on this potentiation, the possibility that theophylline increased adrenal androgen secretion and thereby influenced sexual behaviour, can be ruled out. A major effect of theophylline is to increase levels of cyclic AMP by inhibiting the enzyme which inactivates this nucleotide. These results suggest that cyclic AMP may play a mediating role in the regulation of masculine sexual behaviour by testosterone.
PLASMA TESTOSTERONE CONCENTRATIONS IN THE RAM
Authors: PURVIS K. , ILLIUS A. W. , HAYNES N. B.
Published: December 2008

Testosterone levels in plasma obtained from the jugular vein of rams were measured using a radioimmunoassay. The assay antiserum had a specificity for testosterone such that chromatography was not used during determinations. Blood was taken every ½-1 h under conditions approximating to the natural environment at the particular time of year. Measurements during a 48 h period in January demonstrated that marked episodic bursts of testosterone occurred. Two rams showed eight peaks of testosterone in 24 h with levels reaching 12–14 ng/ml. Two other animals showed four peaks in 24 h, the levels reaching 8 ng/ml. The pattern for all animals was similar in the second 24 h period. In one animal, a testosterone profile obtained over 24 h in the previous November corresponded to that obtained in January although the animal had been serving ewes in the interim period and suggests tentatively that a particular pattern may be inherent in an individual animal.

The rams were maintained in the absence of females until early March and sampled again for 7 h during which time they were allowed contact with an ovariectomized ewe induced into oestrus. The libido of the rams appeared normal. Testosterone levels were low throughout, exceeding 5 ng/ml on one occasion only, and were not affected by copulation. A testosterone profile obtained for two of the rams over a 24 h period in late March demonstrated that the levels were still low. A further testosterone profile was obtained for one of these rams in June. Levels were high and the pattern had reverted to that found the previous November and January.

To obtain evidence that the low levels of testosterone found in March were a result of season rather than lack of regular copulation at this time, blood was obtained from four rams maintained at the Meat and Livestock Commission A.I. Centre, Selby. Two of these animals had not been used for semen collection since January and two were in regular use with a teaser female and semen was collected twice weekly. Maximum testosterone levels of 5 ng/ml were obtained over 12 h in both groups.

During this work, in periods when the testosterone levels were high, there were disruptions in apparently periodic fluctuations in testosterone levels which could be correlated with the proximity of other animals.
THE EXTRACTION OF OESTROGENS, AND THE RATE OF SECRETION OF OESTRONE AND OESTRADIOL-17β BY THE UTERUS IN THE PREGNANT SHEEP
Authors: CHALLIS J. R. G. , HARRISON F. A. , HEAP R. B.
Published: December 2008

The sharp increase in oestrone and oestradiol-17β production during the 48 h before parturition in the ewe does not always result in the uterine venous concentration of these steroids being greater than that found in peripheral blood, even though the gravid uterus is considered to be the major source of enhanced oestrogen synthesis in late pregnancy. This anomaly has been partly resolved by the results from tracer kinetic studies. During the infusion of labelled oestradiol-17β or oestrone into a jugular vein to steady state, 53% of [3H]oestradiol-17β and 62% of [3H]oestrone in the peripheral circulation were extracted by a gravid uterine horn. The extraction of [3H]oestradiol-17α, a product of the infused steroids, was 53% and 45% during the infusion of [3H]oestrone and [3H]oestradiol-17β, respectively.

Calculations of the secretion rate of these steroids by one gravid horn, after correcting for uterine extraction, gave values that represented a substantial proportion of the kinetically determined production rate. This confirms that an appreciable part of the oestrogen produced just before term is in fact derived from the gravid uterus. However, the possibility that other sources may contribute to oestrogen synthesis in late pregnancy cannot be excluded. The findings show that a direct measurement of arteriovenous difference and uterine blood flow is inadequate to determine oestrogen secretion rates by the gravid uterus.
VAGINAL MUCIFICATION IN THE OVARIECTOMIZED RAT IN RESPONSE TO 5α-PREGNANE-3,20-DIONE, TESTOSTERONE AND 5α-ANDROSTAN-17β-OL-3-ONE: TEST FOR PROGESTOGENIC ACTIVITY
Authors: KENNEDY T. G.
Published: December 2008

In an attempt to examine the hypothesis that progesterone, like testosterone, is active through its 5α-reduced metabolite, the ability of 5α-pregnane-3,20-dione (5α-P), testosterone and 5α-androstan-17β-ol-3-one (5α-DHT) to induce vaginal mucification when given subcutaneously for 7 days to oestrogen-pretreated ovariectomized rats was examined. Vaginal mucification was quantified by measuring vaginal sialic acid concentration. When given at the rate of 4 mg/day in either sesame oil or propylene glycol, with or without oestradiol-17β (E2), 5α-P was ineffective in increasing vaginal sialic acid concentration. When given at the rate of 8 mg/day suspended in 16% aqueous gelatin, 5α-P in the absence, but not in the presence of E2, brought about a small increase in vaginal sialic acid concentration. In contrast, testosterone and 5α-DHT, either with or without E2, markedly increased vaginal sialic acid concentration. In terms of its effects on vaginal sialic acid content and concentration, 5α-DHT was estimated to be approximately 45% as potent as testosterone. The difference in the abilities of 5α-P and 5α-DHT to mimic the action on the vagina of progesterone and testosterone, respectively, is discussed.
CORTICOTROPHIN-LIKE PEPTIDES IN THE RAT PITUITARY
Authors: SCOTT A. P. , LOWRY P. J. , RATCLIFFE J. G. , REES LESLEY H. , LANDON J.
Published: December 2008

The pars intermedia of the rat pituitary contains a peptide resembling the 18–39 portion of adrenocorticotrophic hormone (ACTH), which has been termed 'corticotrophin-like intermediate lobe peptide' (CLIP). It can be detected by its cross-reaction with an antiserum directed against the CO2H-terminal portion of the ACTH molecule; it has an amino acid composition identical to the 18–39 portion of human ACTH, except for one less glycine and an extra valine residue, and it is rapidly released from neurointermediate lobes maintained in organ culture. The pars intermedia also contains a peptide with an amino acid composition and biological potency identical to that of melanocyte-stimulating hormone (α-MSH) isolated from other mammals, and which accounts for the bulk of melanocyte-stimulating activity in the pituitary. Rat ACTH resembles human ACTH in amino acid composition, except for an extra valine and one less glycine residue. On the basis of these data it is proposed that ACTH is the precursor of α-MSH and CLIP, which are both present in the cells of the pars intermedia.
PURIFICATION AND CHARACTERIZATION OF PORCINE CORTICOTROPHIN-LIKE INTERMEDIATE LOBE PEPTIDE
Authors: SCOTT A. P. , LOWRY P. J. , BENNETT H. P. J. , McMARTIN C. , RATCLIFFE J. G.
Published: December 2008

Pig posterior pituitary lobe powder contains a peptide structurally identical to the 18–39 portion of porcine adrenocorticotrophin (ACTH). Its extraction by several different procedures is described and its susceptibility to degradation in the presence of 5% acetic acid has been noted. This degradation has been ascribed to the presence of acid proteases in the acetone-dried powder of the posterior pituitary lobe. The peptide has been isolated by chromatography on Biogel P6 and DEAE-cellulose, and characterized by enzyme fragmentation studies. It resembles the peptide isolated from rat neurointermediate lobes termed 'corticotrophin-like intermediate lobe peptide' and it is suggested that it is derived by the intracellular cleavage of ACTH in the pars intermedia cells, with subsequent formation of α-melanocyte-stimulating hormone from the other adrenocorticotrophic fragment.
ELECTROLYTE AND FLUID APPETITE AND BALANCE IN MALE GUINEA-PIGS: EFFECTS OF STILBOESTROL TREATMENT AND RENAL FUNCTION TESTS
Authors: MIDDLETON E. , WILLIAMS P. C.
Published: December 2008

Male guinea-pigs were studied in individual metabolism cages for 6–12 weeks before, and for 13 weeks after, subcutaneous implantation of stilboestrol (15 mg). They were fed on cabbage and either normal pelleted diet (SG1) or sodium-enriched SG1, and had access to either water or to water and 0·86% saline. In all, 42 control and experimental animals were studied and renal function tests were made at 3-week intervals in 18 of them.

The treated animals lost appetite and weight but increased their fluid intake; they showed a preference for saline when this was available and, in doing so, reduced their polydipsia. Fluid and sodium balances were unaffected. The increased sodium appetite, whether satisfied or not, was accompanied by a fall in faecal sodium excretion and a rise in faecal potassium excretion. Renal function tests in themselves also produced some increase in sodium appetite, but no changes in faecal electrolyte excretion. These results suggest strongly that the mechanisms involved in the stimulation of sodium appetite by stilboestrol and renal function tests are different, partly because of the differences mentioned above, but also because the effects of the two procedures when combined were almost exactly additive.

The increased sodium appetite of the treated animals was not explicable by changes in renal function: inulin and creatinine clearances were only slightly reduced and concentrating ability unimpaired. This increased appetite may well be the result of adrenocortical stimulation by stilboestrol acting via extrarenal means.

No change in potassium appetite was observed, possibly because the potassium content of the diet was in excess of requirement. There was a seasonal variation in potassium balance which was lowest in summer in control and treated animals.
AN ASSESSMENT OF THE POSSIBLE ROLE OF 17α,20α-DIHYDROXY-4-PREGNEN-3-ONE IN THE REGULATION OF TESTOSTERONE SYNTHESIS BY RAT AND RABBIT TESTIS
Authors: de BRUIJN H. W. A. , van der MOLEN H. J.
Published: December 2008

17α,20α-Dihydroxy-4-pregnen-3-one is a competitive inhibitor of C17,20-lyase activity in rat testicular tissue in vitro and the significance of this inhibition in vitro was evaluated for testosterone biosynthesis in rat and rabbit testis in vivo. It is concluded that 17α,20α-dihydroxy-4-pregnen-3-one is not involved in the regulation of C17,20-activity in vivo, because it was not possible to detect any 17α,20α-dihydroxy-4-pregnen-3-one in rat and rabbit testicular tissue or in testicular venous blood. If present, the levels are lower than 10 pmol/g testis. Levels of 17α-hydroxyprogester-one are in the order of 50 pmol/g testis. The C17,20-lyase has a higher affinity for 17α-hydroxyprogesterone than for 17α,20α-dihydroxy-4-pregnen-3-one and hence inhibition under in-vivo conditions is not favoured. In rat testes the 20α-hydroxysteroid dehydrogenase activity, which can convert 17α-hydroxyprogesterone to 17α,20α-dihydroxy-4-pregnen-3-one, was found to be mainly (97%) localized in the seminiferous tubules and not at the site of testosterone formation in the interstitial tissue.
THE THYROTROPHIN RECEPTOR IN GUINEA-PIG THYROID HOMOGENATE: GENERAL PROPERTIES
Authors: MANLEY S. W. , BOURKE J. R. , HAWKER R. W.
Published: December 2008

Particulate fractions of guinea-pig thyroid homogenate contained a single class of receptors which bound 125I-labelled bovine thyrotrophin (TSH) by a saturable, reversible process with an affinity constant of 2 × 109 1/mol. The binding process was specific for TSH, and corresponded with the activation of adenylate cyclase. Cleavage of hormone—receptor bonds by treatment with lyotropic agents resulted in the release of unchanged labelled TSH. The radioligand receptor assay system was sensitive to 0·015 mu. TSH. Bovine or mouse thyroid showed reduced binding affinity with correspondingly reduced sensitivity.
EFFECTS OF VASOPRESSIN ON TOAD BLADDER MEMBRANE PROTEINS: RELATIONSHIP TO TRANSPORT OF SODIUM AND WATER
Authors: FERGUSON D. R. , TWITE B. R.
Published: December 2008

The results support previous findings that vasopressin produces dephosphorylation of a toad bladder membrane protein of 50000 mol. wt. At vasopressin concentrations of 50 mu./ml phosphorylation of this protein was 60 ± 7% of the control level, and maximal natriferic and hydro-osmotic responses were observed in intact bladders. However, at concentrations of vasopressin of 10 mu./ml when a maximal natriferic response but no significant hydro-osmotic response were observed, there was no significant difference in phosphorylation of the proteins from control or vasopressin-treated bladders.

We conclude that the 50000 mol. wt membrane protein is likely to be associated with the hydro-osmotic response of the toad bladder to vasopressin.
INACTIVATION OF ARGININE-VASOPRESSIN BY THE ISOLATED PERFUSED RABBIT KIDNEY
Authors: LEVI J. , ROSENFELD S. , KLEEMAN C. R.
Published: December 2008

The ability of the kidney to extract (inactivate and excrete) argininevasopressin (AVP) from the blood was studied in the isolated perfused rabbit kidney. AVP was added to the blood reservoir to give an initial approximate concentration of 100 μu./ml plasma and samples were taken simultaneously from the arterial and venous side at 5, 15, 30 and 45 min. The AVP concentration in the plasma samples was determined by bioassay in the water-loaded, ethanol-anaesthetized rat. The clearance (extraction ratio x renal plasma flow) of AVP from the blood was concentration-dependent. The average extraction ratio ranged from 0·25 at levels of 100 to 44 μu./ml plasma and 0·42 at levels of 44 to 19 μu./ml plasma. The excretion of AVP in the urine was 23% and 29% respectively of the calculated filtered load, in two isolated perfused kidneys, indicating tubular reabsorption and/or tissue inactivation of the filtered hormone.
LACK OF EFFECT OF PINEAL DENERVATION ON THE RESPONSES OF THE FEMALE ALBINO RAT TO EXPOSURE TO CONSTANT LIGHT
Authors: BROWN-GRANT K. , ÖSTBERG A. J. C.
Published: December 2008

Adult female albino rats were exposed to constant light after either a sham operation or bilateral removal of the cervical sympathetic chain. The second operation was later shown to have resulted in the disappearance of all fluorescent fibres from the pineal gland. Despite denervation of the pineal, there was no delay in the onset of persistent vaginal cornification and no significant differences in ovarian weight, sexual receptivity, incidence of ovulation after mating or number of eggs ovulated between the two groups.
INSULIN SECRETORY RESPONSE OF ISOLATED ISLETS OF LANGERHANS IN PREGNANT RATS: EFFECTS OF DIETARY RESTRICTION
Authors: GREEN I. C. , TAYLOR K. W.
Published: December 2008

The effects of diet on the altered insulin secretory responses of islets of Langerhans of pregnant rats have been investigated. The daily food intake of pregnant rats was found to exceed that of control non-pregnant rats by 20% on average. Depriving pregnant rats of this additional food resulted in an alteration in the pattern of insulin secretion seen in pregnancy, such that the sensitivity to stimulation by low glucose concentrations was abolished. The contribution made by different components of the diet to the secretory response in pregnancy was investigated. When additional carbohydrate, though not protein, was fed to pregnant rats on a restricted food intake, the sensitivity of the islets to glucose stimulation was restored. It was concluded that the quantity and in particular the carbohydrate content of food eaten by pregnant rats exerts an important influence on the changes in insulin secretion in pregnancy.
INTERRELATIONSHIP BETWEEN VITAMINS OF THE B-COMPLEX GROUP AND OESTRADIOL
Authors: SHARAF A. , GOMAA N.
Published: December 2008

Vitamins B2 and B6 are shown to have oestrogen-like effects and to act synergistically with oestradiol, increasing its action on the uterine weight of ovariectomized rats. Vitamins B1 and pantothenic acid enhanced the action of oestradiol but had no oestrogenic action themselves. Vitamin B12 had neither an oestrogen-like effect nor an influence on the action of oestradiol.
ALTERATIONS IN INCIDENCE OF MATING AND COPULATION-INDUCED OVULATION AFTER OLFACTORY BULB ABLATION IN FEMALE RATS
Authors: CURRY J. J.
Published: December 2008

Intact control and sham-operated rats, when given sodium pentobarbitone at 13.30 h on the day of pro-oestrus, mated (controls, 10/12; shamoperated, 13/15) that night and underwent copulation-induced ovulation. However, after removal of the olfactory bulbs only 13 out of 23 pentobarbitone-blocked rats mated. Of the mated animals only six ovulated as compared with ten in the unoperated group and ten in the sham-operated group. The incidence of ovulation in all non-mated animals was low. In addition, the bulbectomized, mated animals which ovulated shed significantly fewer ova than did intact controls and sham-operated rats (6·8 as compared with 11·3 and 13·4, respectively). The incidence of mating in bulbectomized animals was also lower than in sham-operated animals when pentobarbitone was not given (8/16 and 8/11, respectively). Ovulation was essentially complete in all groups except in bulbectomized, mated rats which shed significantly fewer ova. It is suggested that olfactory inputs are important in mediating copulation-induced ovulation in the pentobarbitone-blocked rat and that copulation in the absence of olfactory inputs interferes in some way with the normal sequence of secretion of ovulatory hormone(s) in the non-blocked rat.
THE ULTRASTRUCTURE OF THE ACCESSORY SEX ORGANS OF THE MALE RAT: THE EFFECT OF CYPROTERONE ACETATE
Authors: DAHL ERIK , TVETER K. J.
Published: December 2008

The present paper describes the fine structure of the ventral and lateral prostate and the seminal vesicles of the male rat after administration of an anti-androgen, cyproterone acetate, given as subcutaneous injections for varying periods (5–18 days). The treatment caused a general involution with macroscopic atrophy of the organs and reduced the amount of secretory material. There was a marked reduction of both the cell height and width and loss of cytoplasm. The main cytoplasmic changes consisted of a quantitative reduction of the rough endoplasmic reticulum and free ribosomes; the Golgi apparatus was diminished and the number of secretion granules markedly decreased. All the alterations observed are apparently similar to the changes induced by castration.
SEXUAL DIFFERENTIATION IN THE PHASE OF THE CIRCADIAN RHYTHM OF [35S]METHIONINE INCORPORATION INTO CEREBRAL PROTEINS, AND OF SERUM GONADOTROPHIN LEVELS
Authors: ter HAAR M. B. , MacKINNON P. C. B. , BULMER M. G.
Published: December 2008

The incorporation of [35S]methionine into protein in various regions of the brain and in the anterior pituitary, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured at 6 h intervals throughout a 24 h period in the following groups of Wistar rats: (1) normal adult males and females; (2) adult genetic males or females which had been respectively 'feminized' or 'masculinized' by androgen deprivation or administration in neonatal life. Similar measurements were made at 12 h intervals in adult male rats which had been castrated at 7 or 15 days of age.

Serum LH levels showed a circadian rhythmicity in normal adult animals of both sexes, with peak levels in the male occurring 6 h earlier than those in the female. There was no statistically significant circadian rhythm in FSH levels in any group of animals. In all groups of castrated animals LH and FSH levels were raised but no circadian rhythms were observed.

Incorporation of [35S]methionine into protein in all cerebral areas showed circadian rhythms, the peak values of which, in the adult males, were almost 8 h (120°) out of phase with those of the adult females. In the 'feminized' genetic males or 'masculinized' genetic females the rhythmic phase was reversed to that of the opposite genetic sex. Animals castrated at 7 days or 15 days of age did not appear to show a rhythm.

A 12 h rhythm of incorporation was apparent in the anterior pituitary of the normal adult male and the adult 'masculinized' female; no significant rhythm was seen in the normal adult female and the 'feminized' male.

It is suggested that a 'female type' rhythm of incorporation in the brain may be associated with the maintenance of oestrous cycles.
SPLANCHNIC, UTERINE, OVARIAN AND ADRENAL UPTAKE OF PROGESTERONE AND 20α-DIHYDROPROGESTERONE IN THE PREGNANT AND NON-PREGNANT SHEEP
Authors: BEDFORD CECELIA A. , HARRISON F. A. , HEAP R. B.
Published: December 2008

The uptake and extraction of progesterone and 20α-dihydroprogesterone (20α-diHP) by the splanchnic region and by some extra-splanchnic organs was measured by the determination of the concentration of labelled progesterone and 20α-diHP in a carotid artery and in the portal, hepatic, uterine, ovarian and adrenal veins during continuous intravenous infusion of [3H]progesterone.

The efficiency of splanchnic extraction of progesterone and 20α-diHP was 92 and 91%. The splanchnic clearance rates of progesterone and 20α-diHP were 1·210 and 1·223 l/min, respectively. Splanchnic clearance accounted for 27·1% of the metabolic clearance rate of progesterone. The efficiency of extraction of progesterone by some extra-splanchnic organs ranged from 7·9–45·9% across one uterine horn, 5·8–29·9% across one ovary and 30·9–33·3% across one adrenal. For the extraction of 20α-diHP the values were 6·1–9·4% (uterine horn), 15·5% (ovary) and 18·3% (adrenal). In some experiments there was a small production of 20α-diHP across the uterus and ovary. As the blood flow was a relatively small proportion of cardiac output, the clearance rate of progesterone by any one of these sites was less than 0·2% of the metabolic clearance rate.

Labelled progesterone and labelled 5α-pregnanedione were retained in the endometrium (but not in the myometrium) at much higher concentrations than those found in arterial or uterine venous blood. The reduced form, 20α-dihydroprogesterone, was retained in neither the endometrium nor the myometrium. There was a high concentration of polar, conjugated metabolites of progesterone in both uterine tissues compared with that in blood.

The results show that the high metabolic clearance rate of progesterone in the sheep is only partially due to splanchnic (mainly hepatic) uptake, and that over 70% of the progesterone produced is catabolized by extra-splanchnic organs.
STEROID HORMONE ADMINISTRATION AND GONADOTROPHIN SECRETION IN THE GONADECTOMIZED RAT
Authors: BROWN-GRANT K.
Published: December 2008

Facilitation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion by progesterone was demonstrated in female rats ovariectomized 1–2 months previously and primed with oestradiol benzoate or testosterone propionate 72 h before the second injection of steroid. The priming action of testosterone propionate may be due to conversion to oestrogen as the non-aromatizable androgen, 5α-dihydrotestosterone propionate, did not have this effect. None of the steroid hormone treatments tested facilitated LH or FSH release in male rats castrated as adults or in female rats rendered anovulatory by the injection of androgen or oestrogen on day 4 of postnatal life. This abnormality may be the functional basis of the anovulatory state in these animals.

Of the progesterone derivatives tested in the oestrogen-primed ovariectomized rat only pregn-4-en-20α-ol-3-one and 5α-pregnane-3,20-dione significantly stimulated gonadotrophin secretion. These compounds, which are secreted by the rat ovary, may be involved, together with progesterone, in the initiation of the ovulatory surge of gonadotrophin during the oestrous cycle.

The time-course of the changes in gonadotrophin release in the oestrogen-primed ovariectomized rat in response to progesterone was determined. An initial depression was followed by an increase which was more marked for LH than for FSH. Although sodium pentobarbitone administration will prevent or reverse progesterone-induced gonadotrophin secretion, no clear correlation could be established between the sequence of changes in gonadotrophin secretion observed in the present study and the changes in hypothalamic neuronal activity reported by others to follow similar treatment with steroid hormones.
CALCIUM AND THE CONTROL OF CIRCADIAN MITOTIC ACTIVITY IN RAT BONE MARROW AND THYMUS
Authors: HUNT N. H. , PERRIS A. D.
Published: December 2008

Circadian changes in mitotic activity in rat bone marrow and thymus have been demonstrated to closely parallel variations in total and ionized calcium concentrations in plasma. These fluctuations in plasma calcium concentration and tissue mitosis were abolished by parathyroidectomy. Significant changes in plasma phosphate and magnesium concentrations were also observed over the 24 h period. The evidence suggests that hour-to-hour variations in the systems controlling calcium homeostasis determine the levels of mitosis in rat bone marrow and thymus.
GROWTH HORMONE INCREASE DURING SLEEP AFTER DAYTIME EXERCISE
Authors: ADAMSON LIISI , HUNTER W. M. , OGUNREMI O. O. , OSWALD I. , PERCY-ROBB I. W.
Published: December 2008

The effects of strenuous daytime physical exercise were examined in 12 healthy male volunteers. All-night electrophysiological recordings were made and blood was sampled during sleep by indwelling venous catheter.

Plasma growth hormone levels were significantly increased after exercise but the sleep electroencephalographic patterns of nights after exercise did not differ significantly from those of control nights. Plasma corticosteroids were decreased after exercise. It is suggested that higher levels of growth hormone are consistent with reparative processes during sleep.