bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON THE BINDING OF 125I-LABELLED CORTICOTROPHIN TO ISOLATED RAT ADRENOCORTICAL CELLS
Authors: McILHINNEY R. A. J. , SCHULSTER D.
Published: December 2008

Isolated adrenocortical cells, prepared by collagenase disaggregation of normal rat adrenal glands, have been used to study the binding characteristics of 125I-labelled corticotrophin (ACTH) of established biological activity. The binding of the labelled hormone to these whole cells was highly specific, only peptides possessing steroidogenic activity displaced the labelled hormone. Binding was rapid, being complete within 5 min of adding the hormone, and the amount of hormone bound remained constant for up to 20 min thereafter. Over the range 160–10000 pg ACTH/ml, increased binding of the hormone was observed at all concentrations of hormone which stimulated steroidogenesis. However at levels of ACTH which stimulated maximal steroidogenesis there was no saturation of binding. This provides the first direct evidence for the existence of 'spare receptors' for ACTH on whole adrenocortical cells. Scatchard analysis of the binding data suggests that there are two types of receptor for ACTH in this preparation of cells. One receptor is of high affinity (dissociation constant = 2·5 × 10−10 mol/l) about 3000 sites/cell and the other is of lower affinity (dissociation constant = 1 × 10−8 mol/l) with about 30000 sites/cell.
THE SECRETION AND METABOLIC CLEARANCE RATES OF OESTRADIOL IN THE RAT
Authors: TAPPER C. M. , BROWN-GRANT K.
Published: December 2008

The secretion rate (SR) of oestradiol in rats at different stages of the oestrous cycle was determined by measuring the concentration of this hormone in ovarian vein plasma by a competitive protein binding method utilizing rabbit uterine cytosol. The plasma metabolic clearance rate (MCRP) for oestradiol was determined in groups of rats of the same strain and housed under the same conditions by giving a single intravenous injection of tritiated oestradiol-17β and measuring the rate of disappearance of labelled hormone from the plasma. From the relationship SR = MCRP × plasma concentration, predicted values for the plasma oestradiol concentration were obtained and shown to be close to those obtained by direct analysis of peripheral plasma.

The MCRP for oestradiol was not greatly influenced by the stage of the oestrous cycle, the dose of oestradiol-17β injected, ovariectomy 18 h previously or by a sham-operation immediately before the injection of labelled hormone. The anaesthetic used did affect the MCRP; the value for adult female rats injected under ether anaesthesia was about 970 ml/h but under Avertin anaesthesia clearance rates of about 1500 ml/h were obtained. Ligation of the bile duct acutely reduced the MCRP but functional nephrectomy had no immediate effect. Sub-total hepatectomy 18 h previously reduced the MCRP considerably. A small decrease in MCRP was observed when the labelled hormone was administered in third trimester human pregnancy plasma and the MCRP was lower in rats on Day 14 of pregnancy than in rats examined during the oestrous cycle.
PITUITARY HORMONE SECRETION IN THE GENETICALLY MALE RAT PSEUDOHERMAPHRODITE
Authors: GOLDMAN A. S. , ROOT A. W. , DUCKETT G. , SHAPIRO B. H.
Published: December 2008

Pituitary content or concentration of follicle-stimulating hormone (FSH), prolactin and growth hormone in the genetically androgen insensitive male rat pseudohermaphrodite is intermediate between normal male and female rats, while pituitary luteinizing hormone (LH) concentration and serum FSH levels are the same as in the normal male. The concentration of serum LH, prolactin and growth hormone indicates no sexual dimorphism. Although the pseudohermaphrodite is genetically male with a female phenotype, our results suggest some degree of masculinization of the hypothalamicpituitary system.
SEASONAL FACTORS AFFECTING THE RELEASE OF PROLACTIN IN GOATS IN RESPONSE TO MILKING
Authors: HART I. C.
Published: December 2008

An investigation has been carried out in goats of the possible seasonal factors which might influence the autumn decline in the average concentration of prolactin released at milking. Serial blood samples were taken during milking, once a month between August and December 1972, from groups of mated, non-mated and ovariectomized goats and also from goats maintained in summer light conditions (17 h light: 7 h darkness). Since high levels of progesterone occur in the circulation during the major part of the oestrous cycle and pregnancy in the goat, the same sampling procedure was carried out earlier in the year (June–August) in animals which had been implanted with progesterone tablets.

Although high levels of progesterone in the circulation inhibited the release of prolactin at milking, oestrus, mating and pregnancy were not found to be responsible for the fall in prolactin levels in the blood in the autumn. In each of these cases the concentration of prolactin released at milking decreased uniformly between August and October. Housing goats in summer lighting conditions, however, maintained the release of prolactin at milking at a consistently high level from August until December, but had no effect on the milk yield which declined in a manner similar to that of the control animals. It is concluded that daylength is the predominant factor governing the autumn decline in the concentration of prolactin released at milking and that the decline is not the major cause of the fall in milk production during late lactation in goats.
DEVELOPMENT OF PATHWAYS OF INSULIN SECRETION IN THE RABBIT
Authors: MILNER R. D. G. , LEACH F. N. , ASHWORTH M. A. , CSER A. , JACK P. M. B.
Published: December 2008

Insulin release was studied in vitro using pieces of pancreas from rabbits of between 24 days gestational age and 6 weeks postnatal age. When allowance was made for the fraction of pancreas which was endocrine, 16·5 mm-glucose caused increasing stimulation of insulin release as development advanced and 3·3 mm-glucose caused a similar rate of secretion at all ages. Secretion was not significantly influenced by insulin destruction in the incubation medium. Glucagon (5 μg/ml) did not stimulate insulin secretion from 24-day foetal pancreas but did so postnatally. Theophylline (1 mmol/l) stimulated insulin release at all ages and was equipotent on 24-day foetal pancreas in 3·3 or 16·5 mm-glucose. The stimulation of insulin release from 24-day foetal pancreas by 1 mm-theophylline occurred in the absence of extracellular glucose, pyruvate, fumarate and glutamate and in the presence of mannoheptulose and 2-deoxyglucose (each 3 mg/ml). Adrenaline (1 μmol/l) and diazoxide (250 μg/ml) abolished or attenuated the stimulation of insulin release by glucose, leucine plus arginine or theophylline from 24-day foetal, 1 day and 6 weeks postnatal pancreas. The stimulation of insulin release from 6-week-old pancreas by 1 mm-barium was blocked by adrenaline and diazoxide but the effect became less with increasing immaturity.

The experimental results illustrate some of the ways in which insulin secretion by the rabbit β cell changes as a function of development and draw attention to the importance of glucose and cyclic adenosine monophosphate in this process.
THE EFFECTS OF DEXAMETHASONE AND INDOMETHACIN ON THE OUTCOME OF PREGNANCY IN THE RABBIT
Authors: CHALLIS J. R. G. , DAVIES I. J. , RYAN K. J.
Published: December 2008

Pregnant rabbits were treated with indomethacin (8–10 mg/kg/day) or dexamethasone (1·2–1·8 mg/kg/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation were studied. Treatment with indomethacin significantly prolonged the length of gestation (P < 0·01) compared with control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatment reliably induced premature delivery within 3–6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF.

These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.
PHYSIOLOGICAL VARIATION IN ABUNDANCE OF OESTROGEN SPECIFIC HIGH-AFFINITY BINDING SITES IN HYPOTHALAMUS, PITUITARY AND UTERUS OF THE RAT
Authors: GINSBURG M. , MACLUSKY N. J. , MORRIS I. D. , THOMAS P. J.
Published: December 2008

High-affinity binding of [2,4,6,7-3H]oestradiol-17β has been studied in cytosols prepared from hypothalami, pituitaries and uteri of female rats killed at different stages of the oestrous cycle, and in cytosols prepared from the hypothalami and pituitaries of male rats. In all cases the equilibrium dissociation constant of reaction was of the order of 10−10 mol/l. The number of available high affinity sites per tissue (n) varied with physiological state. In females, n fluctuated with the oestrous cycle. In hypothalamus and pituitary, n fell by about 60 and 40% respectively in pro-oestrus, replenishment occurred during oestrus but could be delayed by phenobarbitone administration during the afternoon of pro-oestrus. In the uterus, n varied biphasically, there being peaks during dioestrus and oestrus, and troughs at pro-oestrus and metoestrus. The numbers of available sites at metoestrus were 12·5 × 109, 10·6 × 1010 and 24·4 × 1010 for hypothalamus, pituitary and uterus respectively. In male rats, values for n were similar to those obtained for females at pro-oestrus (n/hypothalamus = 6·8 × 109, n/pituitary = 4·2 × 1010). Binding was oestrogen specific in all the tissues studied.
THE ROLE OF SHORT DAYS IN THE TERMINATION OF PHOTOREFRACTORINESS IN FEMALE CANARIES (SERINUS CANARIUS)
Authors: STEEL ELIZABETH , FOLLETT B. K. , HINDE R. A.
Published: December 2008

Photorefractory intact female canaries were exposed to a photoperiod of 8 h light: 16 h darkness (8L: 16D) for 0, 2, 4 or 6 weeks before photostimulation with 14L:10D for 4 weeks. Photoresponsiveness was measured in terms of plasma immunoreactive LH, ovary and oviduct weights, follicle size and nest-building behaviour. Birds not exposed to 8L:16D were unresponsive to photostimulation while those exposed for 6 weeks to 8L: 16D were as fully photosensitive as females similarly treated immediately before their first breeding season. Birds exposed for 2 or 4 weeks to 8L:16D responded to subsequent photostimulation but were not as responsive as birds exposed to short days for 6 weeks. Positive correlations between the two ovarian parameters and between these ovarian parameters and oviductal weight existed in all groups exposed to short days, but not in birds not exposed to short days. It is concluded that the restoration of photosensitivity at the end of the refractory period is a function of the number of short days experienced; about 6 weeks of short days are needed for its completion.

In another experiment photorefractory birds exposed for 6 weeks to short days without subsequent photostimulation, although potentially photosensitive, were indistinguishable (in terms of the above parameters) from refractory birds kept on long days for the same period; in these birds refractoriness was not broken.
CONTROL OF SEBACEOUS GLAND FUNCTION IN THE RAT BY α-MELANOCYTE-STIMULATING HORMONE
Authors: THODY A. J. , SHUSTER S.
Published: December 2008

The effect of α-MSH on sebum secretion and preputial gland weight was examined in intact, castrated and hypophysectomized male rats and in hypophysectomized rats receiving treatment with either testosterone propionate (TP) or progesterone. After treatment with α-MSHMSH for 2 weeks, increases in sebum secretion occurred in intact, castrated and hypophysectomized rats, but larger responses were found in the hypophysectomized rats that had received treatment with either TP or progesterone, suggesting that α-MSH acts synergistically with TP and progesterone to stimulate sebum secretion. α-Melanocyte-stimulating hormone also increased preputial gland weight in intact rats, but there was no response after castration and only a small response after hypophysectomy. However, when the hypophysectomized rats received simultaneous treatment with either TP or progesterone, α-MSH increased preputial gland weight.

It is suggested that α-MSH acts directly on the sebaceous glands to stimulate lipogenesis and, together with steroid hormones, may have an important role in controlling sebaceous gland function in the rat and other hairy mammals. With the evolution of hair, certain of the MSH peptides may have lost their significance as pigmentary hormones and have developed a sebotrophic function. For this reason, it might be more appropriate to refer to these peptides as the 'sebotrophins'.
CHANGES IN THE CONCENTRATION OF FOLLICLE-STIMULATING HORMONE IN PLASMA DURING DEVELOPMENT IN THE GUINEA-PIG
Authors: DONOVAN B. T. , TER HAAR M. B. , LOCKHART A. N. , PEDDIE M. J.
Published: December 2008

The concentration of FSH in the plasma of guinea-pigs from day 50 of gestation to day 45 of postnatal life was assayed by a radioimmunological procedure utilizing a cross-reaction with the NIAMDD S6 antiserum to rat FSH.

At 68 days of gestation the mean plasma FSH concentration of female foetuses was greater than that of the males, although the concentrations in the two sexes were similar on day 50 of gestation. Maternal levels remained consistently low throughout gestation. Postnatally there were no marked changes in plasma FSH levels through to maturity, although a transient rise in the male occurred over the first 3 days after birth.

Gonadectomy on days 0, 5, 10, 15, 25 or 35 of postnatal life, or when adult, resulted in a significant increase in plasma levels of FSH within 10 days. The rise in plasma FSH concentration was greater in males than in females at all ages, although a larger increase was observed in females spayed at 5 or 10 days of age than at other times.
DEMONSTRATION OF A SPECIFIC CYTOSOL RECEPTOR IN THE NORMAL AND HYPERPLASTIC CANINE PROSTATE FOR 5α-ANDROSTANE-3α, 17α-DIOL
Authors: EVANS C. R. , PIERREPOINT C. G.
Published: December 2008

A specific receptor protein has been demonstrated for 5α-androstane-3α, 17α-diol in cytoplasmic extracts of normal and hyperplastic canine prostates. The receptor molecule, with a sedimentation coefficient of 4–5S, has been identified by the use of sucrose gradient centrifugation of tissue fractions which had been labelled in vitro with tritiated 5α-androstane-3α, 17α-diol. The receptor showed a relatively high affinity for this compound whereas binding could not be demonstrated with other labelled C19 steroids. In addition binding of tritiated 5α-androstane-3α, 17α-diol was not affected by the presence of 50-fold excesses of other C19 steroids.
PLASMA HORMONES AND PITUITARY LUTEINIZING HORMONE IN THE RAT DURING THE EARLY STAGES OF PREGNANCY AND AFTER POST-COITAL TREATMENT WITH TAMOXIFEN (ICI 46,474)
Authors: WATSON J. , ANDERSON F. B. , ALAM M. , O'GRADY J. E. , HEALD P. J.
Published: December 2008

Plasma levels of oestradiol-17β, progesterone and luteinizing hormone (LH) and pituitary levels of LH have been measured during the first 6 days of pregnancy, in normal rats and in rats receiving two doses of Tamoxifen (trans-1-(p-β dimethylamino-ethoxyphenyl)-1-2 diphenylbut-1-ene) on day 2 of pregnancy.

In normal rats oestradiol rose strongly from early on day 3 to reach a peak concentration between 22.00 h on day 3 and 08.00 h on day 4. Progesterone concentrations rose from day 2 to reach peak values on day 3–4. In animals in which implantation was delayed 20–24 h by administration of Tamoxifen (0·1 mg/kg) orally on day 2 the increased level of plasma oestrogen was also delayed by 20 h. A higher dose of Tamoxifen (0·2 mg/kg) on day 2, which prevented implantation, completely eliminated the increase in plasma oestradiol. Neither dose of Tamoxifen affected the levels of progesterone.

In both normal rats and rats treated with 0·1 mg Tamoxifen/kg, plasma LH levels declined by day 3 while pituitary levels rose steadily. There was no detectable change in either plasma or pituitary LH levels, accompanying the increase in plasma oestradiol in the normal rats. In animals receiving Tamoxifen (0·2 mg/kg), plasma LH increased to a maximum by day 4 while levels of pituitary LH decreased.

The results show that the oestrogen ' surge' of early pregnancy, occurs normally about midnight on day 3 and not late on day 4 as previously thought. It is considered that the plasma oestradiol peak in early pregnancy results from an increased release of FSH rather than an increased release of LH. Tamoxifen may owe part of its antifertility action to a capacity to inhibit the synthesis of oestradiol from progesterone.
PRODUCTION OF SPECIFIC ANTISERA TO FOLLICLE-STIMULATING HORMONE AND OTHER HORMONES
Authors: LYNCH S. S. , SHIRLEY A.
Published: December 2008

Specific high titre antisera were raised in three out of four rabbits injected with 100/μg each of a highly purified FSH preparation by the multi-site intradermal immunization technique. High titre antisera were also raised to LH, TSH, HCG, and the α sub-unit of HCG. Immunization with human GH- and LH-releasing hormone did not result in such high titre antisera. The implications of the results are discussed.
REVERSAL BY PROGESTERONE OF PHENOBARBITONEBLOCKADE OF OVULATION IN THE PREPUBERTAL RAT PRIMED WITH PREGNANT MARE SERUM GONADOTROPHIN
Authors: McCORMACK C. E. , STRAUSS W. F.
Published: December 2008

In immature female rats injected with PMSG at 30 days of age (day 30), ovulation occurs between the hours of 02.00 and 03.00 on day 33. If progesterone is injected at 10.00 h on day 32, the onset of ovulation is advanced by 1–2 h. In rats that were not given progesterone, ovulation was blocked by phenobarbitone sodium administered on day 32 before 13.50 h. However, pretreatment with progesterone at 10.00 h caused ovulation to occur in spite of phenobarbitone treatment at 13.50 h. An early release of ovulatory gonadotrophin from the anterior pituitary gland cannot completely account for progesterone's capacity to reverse the blockade of ovulation by phenobarbitone, because when phenobarbitone treatment was advanced by 2–4 h, ovulation still occurred in most progesterone-treated rats.
UPTAKE OF 125I-LABELLED HUMAN PLACENTAL LACTOGEN AND HUMAN PLACENTAL LACTOGEN BY THE TISSUES OF NORMAL AND LACTATING RATS
Authors: REDDY S. , WATKINS W. B.
Published: December 2008

The rate of clearance from the circulation and uptake into tissues of radioactive label was studied after i.v. injection of 125I-labelled human placental lactogen (HPL) into rats at various stages of pregnancy. The half-life was obtained for the disappearance of the trichloroacetic acid-precipitable material from the plasma. The half-life, t½(S), calculated over the first 5 min after injection of the hormone was 5·4 ± 1·1 (s.d.) min, while a half-life, t½(L), of 27·9 ± 2·3 min was obtained from the decay period of 15–35 min.

In the non-pregnant and pregnant rat the highest ratio of the radioactivity in an organ to that in the blood was 12–14:1 in the kidney. That the kidney is mainly involved in the uptake of exogenous HPL is further confirmed by the application of the histochemical immunoperoxidase technique. Human placental lactogen was localized in the cells of the proximal tubules of the cortex and to a lesser extent in the tubular lumen and the tubules of the medulla region.

Uptake of HPL in vivo also occurs in the mammary gland tissue of the post-partum rat and reaches a maximum uptake between 15 and 30 min after injection of the hormone. Furthermore, specific uptake of HPL was observed on the alveolar cell membranes after the incubation of paraffin-embedded sections of formalin-fixed mammary gland and subsequent treatment by the peroxidase-labelled antibody method.

These findings support the work of others who have demonstrated the presence of specific membrane receptors in the mammary gland for hormones with prolactin-like activity.
CHANGES IN THE ENDOMETRIUM OF MICE AFTER THE INDUCTION OF IMPLANTATION BY ACTINOMYCIN D
Authors: FINN C. A. , DOWNIE JENIFER M.
Published: December 2008

Actinomycin D can induce a small number of implantations in pregnant mice undergoing progestin-induced delayed implantation following ovariectomy. However, the response of the uterus to the blastocyst is considerably retarded compared with the response observed when implantation is precipitated by oestradiol.

With the electron microscope the attachment reaction between the trophoblast and uterine epithelium is evident about 48 h after administration of the drug. However, the differentiation of the luminal surface of the epithelial cells in areas of uterus distant from a blastocyst (2nd stage of closure), which normally accompanies implantation, and can be induced by oestradiol in progesterone-treated animals, is not seen. Thus actinomycin D, although allowing implantation to proceed, does not completely mimic the actions of oestradiol on the progesterone-treated uterus.
DISCREPANCY BETWEEN RADIOIMMUNOASSAY AND RADIOLIGAND-RECEPTOR ASSAY OF LUTEINIZING HORMONE RELEASED IN VITRO BY PITUITARY TISSUE FROM MALE RATS OF DIFFERENT AGES
Authors: SHARPE R. M. , SHAHMANESH M. , ELLWOOD M. G. , HARTOG M. , BROWN P. S.
Published: December 2008

Anterior pituitary glands from male rats aged 21, 40, 60 or 95 days were incubated in medium containing 0, 2 or 20 ng luteinizing hormone-releasing hormone (LH-RH)/ml. Incubates were assayed for LH by radioimmunoassay (RIA), by the radioligand-receptor assay (RLA) using testicular homogenates as the source of receptor and, in some instances, by the ovarian ascorbic acid depletion assay (OAAD). Irrespective of the dose of added LH-RH, glands from rats aged 40 and 60 days always showed a higher release of LH, as determined by RLA, than glands from animals aged 21 or 95 days. Measurement by RIA showed a similar pattern to RLA in the basal release of LH, but in the presence of LH-RH showed little difference in LH release by glands from rats aged 40, 60 or 95 days. The LH release caused by the higher concentration of LH-RH was always greater when measured by RLA than by RIA. Assay of comparable incubates by OAAD showed close agreement with RLA estimates in four incubations (mean index of discrimination 1·07; range 0·86–1·18) and consistent disagreement with RIA estimates (1·64; range 1·38–1·99). In contrast to the results with incubates, homogenates of pituitary glands from male rats of various ages showed close agreement of estimates by RLA, RIA and OAAD. These results suggest that RIA underestimates the LH-RH-stimulated release of LH in vitro from the male rat pituitary during some stages of sexual maturation.
THE PRODUCTION OF CARDIAC HYPERTROPHY BY TRI-IODOTHYROACETIC ACID
Authors: SYMONS CECIL , OLSEN E. G. J. , HAWKEY C. M.
Published: December 2008

Severe cardiac hypertrophy has been produced experimentally in rats by long-term, lowdose treatment with tri-iodothyroacetic acid. The dose used was insufficient to cause any apparent systemic or metabolic effect. It is suggested that similar iodinated substances in the blood in man, resulting from normal or abnormal thyroid hormone catabolism, may be causally related to some forms of cardiomyopathy.
THE PROLIFERATIVE RESPONSE OF THE COAGULATING GLAND OF THE CASTRATED MOUSE UNDER CONTINUOUS ANDROGEN STIMULATION: AN EXPERIMENTAL AND COMPUTER SIMULATION MODEL
Authors: MORLEY A. R. , APPLETON D. R. , WRIGHT N. A. , ALISON M. R.
Published: December 2008

The proliferative response of the coagulating gland of the castrated male mouse has been examined during continuous treatment with testosterone propionate. Fourteen days after castration, s.c. daily injections of testosterone propionate were begun. Mitotic (Im) and labelling (IL) index values were obtained at 3 h intervals for up to 100 h after the initial injection. These showed a biphasic response, in which IL reached a maximum at 30 and 70 h, and Im at approximately 45 and 75 h. Fraction-labelled mitoses (FLM) curves were begun 24, 48, and 72 h after the first androgen injection. In each curve the first wave of labelled mitoses rose to 100% and showed a square form indicating little spread in the durations of the G2 and S phases. Values of 7·5, 1·3 and 0·7 h, were obtained for the durations of DNA synthesis (ts), the post-synthetic period (tG2) and of mitosis (tm) respectively. In none of the FLM curves was it possible to demonstrate a second wave of labelled mitoses and direct measurement of the cell cycle time (Tc) was not obtained. Continuous tritiated thymidine labelling indices revealed that after a latent period of 25 h, DNA synthesis began and labelling rose rapidly to 80% by 45 h and then more slowly to 95% by 97 h. Cell population changes during androgen stimulation estimated from measurements of total glandular DNA indicated that the number of cells present in the glands remained constant during the first 30 h after stimulation and thereafter increased to approximately 2·3 times the original value.

The data are compared with a mathematical model which assumes that the cell population of castrated mice when stimulated passes from a G0 compartment through successive waves of DNA synthesis and mitosis. After each cell division the cells may leave or remain in the proliferative cycle. This model has been subjected to computer simulation using the cell cycle parameters obtained in the kinetic experiments. There was good agreement between the simulation and experimental results in the Im and IL curves, continuous labelling, and total cell number experiments. The simulation of FLM curves was less successful. Although the first wave of labelled mitoses was clearly seen the model predicts a distinct second wave of labelled mitoses. It is concluded that this does not appear because of variation in the duration of G1.
EVIDENCE FOR A POSSIBLE FOETAL CONTROL OF PROSTAGLANDIN RELEASE FROM THE PREGNANT RAT UTERUS IN VITRO
Authors: PARNHAM M. J. , SNEDDON J. M. , WILLIAMS K. I.
Published: December 2008

The release of prostaglandin-like material and the spontaneous contractions of individual horns from the pregnant rat uterus in vitro have been studied on day 22 of pregnancy – the expected day of delivery. Removal of foetuses (retaining placentae in utero) from one or both uterine horns on day 16 or 17 significantly reduced prostaglandin F release and spontaneous activity. Rats which had been made unilaterally pregnant after ligation of one uterine horn, exhibited a decrease in prostaglandin F output from both horns. Uterine activity and prostaglandin release were increased in quiescent uteri by the addition of arachidonic acid (5 μg/ml) or phospholipase A (160 mu./ml); these effects were abolished by indomethacin (20 μg/ml). However, the stimulation of uterine activity by PGF2α (30–60 ng/ml) was not affected by indomethacin. It is concluded that the release of prostaglandins from the pregnant rat uterus in vitro at term is related to the presence of viable foetuses.
MECHANISM OF ACTION OF GLUCOCORTICOIDS IN INDUCTION OF OVINE PARTURITION: EFFECT ON PLACENTAL STEROID METABOLISM
Authors: ANDERSON ANNE B. M. , FLINT A. P. F. , TURNBULL A. C.
Published: December 2008

Maternal plasma progesterone levels in sheep may fall dramatically during the last few days of gestation and following the administration of glucocorticoids to the foetus. To investigate the mechanism of the fall, metabolism of [3H]pregnenolone and/or [3H]progesterone in vitro by ovine placental tissue was studied in five ewes before and after intra-foetal administration of dexamethasone in a dosage sufficient to induce parturition, and in one ewe after the spontaneous onset of labour at 143 days of gestation. Manual separation of maternal and foetal placental tissues showed that, in 11 out of 12 cases, the foetal and not the maternal placenta produced progesterone from pregnenolone in vitro. Total activities of cholesterol side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase in the foetal placenta were not influenced by intra-foetal dexamethasone. Before administration of dexamethasone, homogenates of foetal placenta converted [3H]progesterone to 20α-hydroxy [3H]pregn-4-en3-one in the presence of NADPH. Within 12 h of administration of dexamethasone, and after the natural onset of labour at 143 days, large amounts of 17α,20α-dihydroxy[3H]pregn4-en-3-one were formed from [3H]progesterone. Intra-foetal dexamethasone treatment also induced the formation of 17α,20α-dihydroxy[3H]pregn-4-en-3-one by minced foetal placental tissue incubated with [3H]pregnenolone. This change in steroid metabolism did not occur in foetal placental tissue from a sham-operated animal receiving no dexamethasone. Assay of progesterone in foetal placentae showed that the increased formation of 17α,20αdihydroxypregn-4-en-3-one was unlikely to be caused by a change in the specific activity of added 3H-labelled precursor, although the production of 17α,20α-dihydroxypregn-4-en3-one in vitro increased at a time when both foetal placental and utero-ovarian venous levels of progesterone were decreasing in response to dexamethasone treatment. These observations indicate that intra-foetal dexamethasone treatment induces a placental 17α-hydroxylase enzyme, which is also present in foetal placental tissue after the spontaneous onset of labour at term.
EFFECTS OF ACUTE AND CHRONIC STRESS ON PLASMA CORTICOSTERONE LEVELS IN THE PREGNANT AND NON-PREGNANT MOUSE
Authors: BARLOW SUSAN M. , MORRISON P. J. , SULLIVAN F. M.
Published: December 2008

Plasma corticosterone levels were measured in the pregnant and non-pregnant mouse after acute and chronic stress. Acute surgical stress in the non-pregnant mouse increased plasma corticosterone from a mean resting level of 2·3 to 50·6 μg/100 ml 1 h after operation. By 24 h after operation, levels had fallen back to 7·6 μg/100 ml. In the pregnant mouse an acute surgical stress on day 14 of pregnancy increased plasma corticosterone levels to 525 μg/100 ml 1 h after surgery from a resting value of 80 μg/100 ml, with a return to resting levels by 24 h. During the chronic stress of 24 h restraint, plasma corticosterone levels in the non-pregnant mouse reached a peak (81·0 μg/100 ml) 1 h after the start of restraint and were still raised (mean 24·0 μg/100 ml) after 24 h. In the pregnant restrained mouse a peak value of 733 μg/100 ml was seen at 1 h, with levels maintained at around 500–600 μg/100 ml during the next 16 h of restraint. Increased levels of 268 μg/100 ml were still present at 24 h. After the chronic stress of 24 h food deprivation, plasma corticosterone levels in the non-pregnant and pregnant mice were raised after 7 h to levels slightly lower than those observed in the restrained groups, and at 24 h levels in the respective restrained and fooddeprived groups were similar, suggesting that food deprivation is a powerful chronic stressor in the mouse.

During chronic stress in the pregnant mouse where plasma corticosterone levels of around 600 μg/100 ml were maintained for some hours, protein binding studies indicated that 10 μg/100 ml was free, unbound corticosterone. The physiological and pathological consequences of such high levels of free corticosterone during stress in pregnancy are discussed.
FURTHER STUDIES ON THE AFFERENT PATH OF THE MILK-EJECTION REFLEX IN THE BRAIN STEM OF THE RABBIT
Authors: TINDAL J. S. , KNAGGS G. S.
Published: December 2008

When the afferent pathway of the milk-ejection reflex, which we had previously reported, was surgically severed bilaterally in the mid-brain of the lactating rabbit, the reflex release of oxytocin in response to suckling was blocked for up to 11 days; unilateral severance did not block the reflex. The position and discrete nature of the pathway were also further substantiated by electrical stimulation experiments in acute studies in the anaesthetized rabbit. Some animals, however, did not release oxytocin in response to stimulation of the pathway. Furthermore, whereas stimulation of this reflex pathway in the guinea-pig brain at intervals of a few minutes evokes release of oxytocin after each stimulation, in the present study the release of oxytocin in the rabbit in response to repeated electrical stimulation was either progressively attenuated or did not occur at all after the initial release. There appears, therefore, to be a powerful overriding central inhibitory mechanism in the rabbit which can prevent release of oxytocin, even when the appropriate stimulus for release is applied.
A NEW METHOD FOR THE PRODUCTION OF EXPERIMENTAL DIABETES IN RABBITS
Authors: PAKRASHI ANITA , MUKHERJEE SAMIR K.
Published: December 2008

Oral administration of 250 mg hydrochlorothiazide/kg, with previous i.v. injection of 4 i.u. soluble insulin or s.c. injection of protamine-zinc insulin, has been found to produce stable hyperglycaemia in rabbits irrespective of sex. It is thought that insulin helps the selective action of hydrochlorothiazide on the β cells by removing the protective glucose barrier. Although stimulation of glucagon or some extra-pancreatic mechanism at the initial stage could not be altogether ruled out, the central action of the drug is supported by the finding that the hydrochlorothiazide-induced hyperglycaemia was lowered by the sulphonylurea derivative, chlorpropamide.
INFLUENCE OF ANAESTHETICS ON BASAL, PERPHENAZINE-INDUCED AND THYROTROPHIN RELEASING HORMONE-INDUCED PROLACTIN SECRETION IN OVARIECTOMIZED, OESTROGEN-TREATED RATS
Authors: LAWSON D. M. , GALA R. R.
Published: December 2008

Plasma levels of prolactin were determined, by radioimmunoassay, in ovariectomized, oestrogen-treated rats after administration of ether, sodium pentobarbitone, urethane, chloral hydrate or ketamine. These anaesthetics, when administered alone, induced sustained increases in the plasma level of prolactin (continuous ether inhalation), no change in prolactin secretion (urethane), or depressions in the level of prolactin (sodium pentobarbitone, chloral hydrate and ketamine). These same anaesthetics when given before perphenazine failed to alter the stimulatory effect of this phenothiazine on prolactin secretion. Sodium pentobarbitone did not alter the normal increase in prolactin concentration after intra-arterial administration of synthetic thyrotrophin releasing hormone (TRH). These results indicated that anaesthetics do not affect the response of either the central nervous system or the anterior pituitary to perphenazine or TRH although they affect prolactin secretion when administered alone. The site of action of anaesthetics must, therefore, be different from that of perphenazine or perphenazine must be capable of overcoming their influence by direct action on the pituitary.
MAINTENANCE OF MALE SEXUAL BEHAVIOUR BY COMBINED TREATMENT WITH OESTROGEN AND DIHYDROTESTOSTERONE IN CD-1 MICE
Authors: WALLIS C. J. , LUTTGE W. G.
Published: December 2008

After castration, adult male sexually experienced CD-1 strain mice were treated with dihydrotestosterone (200 μg/day, DHT), oestradiol benzoate (1 μg/day, OB) or DHT (200 μg/ day) plus OB (1 μg/day). Oestradiol benzoate and the combined treatment DHT+OB maintained male sexual behaviour at levels comparable to a group of intact control mice, while DHT maintained behaviour at a lower level. Halving all hormone dosages resulted in a decrease in the number of OB-treated animals mating and a complete loss of mating in the DHT-treated animals. The decrease in dosage did not result in any change in the behaviour of the mice receiving both hormones. Adrenalectomy was found to have no effect on the mating behaviour of the OB-treated and untreated animals, but it did reduce the number of DHT+OB-treated animals mating. Thus, both OB alone and combined DHT+OB treatment can maintain male mating behaviour in castrated CD-1 strain mice and these effects do not appear to be due to the effects of oestradiol on the adrenal.
EFFECT OF IONIC STRENGTH AND IONIC COMPOSITION OF ASSAY BUFFERS ON THE INTERACTION OF THYROXINE WITH PLASMA PROTEINS
Authors: SUTHERLAND R. L. , BRANDON M. R. , SIMPSON-MORGAN M. W.
Published: December 2008

When plasma proteins are diluted with buffer the ionic strength and ionic composition of that buffer affects the interactions between thyroxine (T4) and its plasma protein-binding sites. Increases in phosphate, chloride or barbiturate ion concentration from 50 to 200 mmol/l caused a significant decrease in the affinity of plasma proteins for T4, and a concurrent increase in the concentration of unbound T4. These results cannot be completely accounted for by changes in ionic strength since at the same ionic strength different anions caused quantitatively different effects on unbound T4 concentration. The degree of depression of T4 binding by the three anions studied was in the order barbiturate > chloride > phosphate.

The results of a systematic study on the composition of diluent buffer systems indicated that when a 50 mm-sodium phosphate–100 mm-NaCl buffer (pH 7·4) was used as a plasma diluent, there were unlikely to be gross changes in the T4-binding properties of plasma proteins with dilution.
THE EFFECTS OF HYPOPHYSECTOMY AND OF BOVINE GROWTH HORMONE ON THE RESPONSES TO TESTOSTERONE OF PROSTATE, PREPUTIAL, HARDERIAN AND LACHRYMAL GLANDS AND OF BROWN ADIPOSE TISSUE IN THE RAT
Authors: EBLING F. J. , EBLING ERIKA , RANDALL VALERIE , SKINNER J.
Published: December 2008

The relative responses to testosterone of the prostate, preputial, Harderian, and lachrymal glands, the seminal vesicles and the brown adipose tissue, have been compared in litter-mate, castrated and hypophysectomized–castrated rats, with or without treatment with bovine GH. The responses of both prostate and preputial glands, though not the seminal vesicles, were reduced by hypophysectomy, and restored by GH. Growth hormone had some independent action on the preputial glands, but most of its effect was synergistic with testosterone. The response of brown adipose tissue to testosterone was similarly reduced by hypophysectomy, but was not restored by the GH. The weights of the Harderian and lachrymal glands were not affected by castration, but they were considerably reduced by hypophysectomy. Growth hormone had a slight restorative effect on the Harderian glands, but none on the lachrymal glands.
DIFFERENCES IN SERUM CORTICOSTERONE PATTERNS IN INDIVIDUAL RATS: RELATIONSHIP TO OVULATORY CYCLES
Authors: RAMALEY JUDITH A.
Published: December 2008

Blood samples were collected on several occasions from Sprague–Dawley–derived rats by means of cardiac puncture at 8 h intervals over a 24 h period. Rats were sampled four times before ovariectomy, after ovariectomy and after replacement therapy with oestradiol benzoate. It was discovered that each rat tended to maintain a distinct pattern of serum corticosterone. While some rats developed hormonal rhythms, other rats showed no evidence of such rhythms as indicated by patterns of serum corticosterone concentration. The majority of rats that did not show daily corticosterone rhythms were found to have irregular ovulatory cycles as indicated by vaginal smears. Each characteristic hormonal pattern remained after ovariectomy and subsequent oestrogen replacement although resting levels of corticosterone were lower after ovariectomy and higher after oestrogen treatment than before the operation. It is concluded that the presence of an adrenal rhythm is usually associated with regular vaginal smear cycles.
EFFECTS OF OVARIAN STEROIDS AND PROLACTIN ON THE SEQUENTIAL DEVELOPMENT OF NESTING BEHAVIOUR IN FEMALE BUDGERIGARS
Authors: HUTCHISON R. E.
Published: December 2008

As intact, breeding female budgerigars approach egg-laying, they spend an increasing amount of time in the nestbox and nest hollow. The brood patch area begins to defeather and becomes vascular and the oviduct increases in weight. Precursory albumen forms in the tubular glands of the oviduct.

Oestradiol (OB) treatment in combination with prolactin (OB + PL) induced ovariectomized budgerigars to display nesting behaviour which did not differ from that shown by intact females in the 3 days immediately preceding egg-laying. In contrast, OB induced only the initial phase of the nesting sequence and the effects of OB in combination with progesterone (OB + PR) were intermediate between treatments with OB alone and OB + PL. Incubation of artificial eggs occurred only in the OB + PL group and the latency to display of the incubation posture was shorter in the OB + PL group than in the OB + PR group.

No incubation posture was displayed by the OB-treated group.

Oviduct development was not influenced by prolactin, but progesterone induced precocious development of tubular glands in the magnum region of the oviduct. Treatment with OB + PR induced uniform development of precursor albumen in the tubular glands. Development of the brood patch occurred with both OB + PL and OB + PR treatment. However, OB + PR resulted in defeathering which was advanced in relation to vascularity when compared with intact breeding females, whereas defeathering and vascularity of the OB + PL group did not differ from that of intact females at egg-laying.

These results indicate that prolactin in combination with oestradiol was more effective than progesterone not only in inducing the later phases of nesting behaviour but also in initiating incubation behaviour and defeathering of the brood patch area.
EFFECTS OF TESTOSTERONE MEDIATED OR MODULATED BY PITUITARY FACTORS
Authors: DE MOOR P. , ADAM-HEYLEN M. , VAN BAELEN H. , VERHOEVEN G.
Published: December 2008

Adult rats of both sexes were either gonadectomized or hypophysectomized and gonadectomized. Three to eight weeks later they were treated for 14 consecutive days with oil or with 75 or 200 μg testosterone propionate (TP) per 100 g body weight. The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3α-hydroxysteroid dehydrogenases (3α-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned. For two of the latter, i.e. the relative kidney and prostatic weights, no significant differences were found.

Transcortin levels, relative adrenal weights and renal NADPH-dependent 3α-HSD activities were higher in oil-treated gonadectomized animals than in oil-treated hypophysectomized-gonadectomized animals. The opposite was found for the relative weights of uterus and seminal vesicles and renal NADH-dependent 3α-HSD activities. These differences between gonadectomized and hypophysectomized-gonadectomized animals disappeared after TP treatment as far as transcortin levels were concerned but remained for the five other parameters.

After gonadectomy sexual differences subsisted for all parameters studied. But whereas intact male rats had higher NADH-dependent 3α-HSD activities than female rats the opposite was found after gonadectomy. After gonadectomy plus hypophysectomy the between sex differences disappeared as far as transcortin levels were concerned but remained in the other parameters studied.
INCREASED CONCENTRATIONS OF 17α,20α-DIHYDROXYPREGN-4-EN-3-ONE IN MATERNAL AND FOETAL PLASMA NEAR PARTURITION IN SHEEP
Authors: FLINT A. P. F. , GOODSON JANE D. , TURNBULL A. C.
Published: December 2008

Using specific radioimmunoassays, 17α,20α-dihydroxypregn-4-en-3-one and progesterone were measured in maternal utero-ovarian venous plasma from four sheep during parturition induced with dexamethasone and two sheep at spontaneous delivery. 17α,20α-Dinydroxypregn-4-en-3-one was also measured in maternal jugular venous and foetal posterior vena caval plasma from one dexamethasone-induced animal over the same period. Basal utero-ovarian venous levels of 17α,20α-dihydroxypregn-4-en-3-one were in the range 3– 7 ng/ml; at the time of the pre-labour fall in maternal progesterone, the concentration of 17α,20α-dihydroxypregn-4-en-3-one increased, reaching 17–76 ng/ml at delivery. Maternal levels fell rapidly after delivery. In contrast to foetal progesterone concentrations, which are low, foetal 17α,20α-dihydroxypregn-4-en-3-one levels were approximately the same as those in the maternal utero-ovarian vein. Maternal jugular venous levels in one animal were 50–80% of those in the utero-ovarian vein. These findings confirm earlier results obtained in vitro which indicated that exposure to glucocorticoid results in increased activity of a steroid 17α-hydroxylase in the ovine foetal placenta.
A COMPARISON OF VARIATIONS IN PLASMA LUTEINIZING HORMONE CONCENTRATIONS IN MALE AND FEMALE DOMESTIC CHICKENS (GALLUS DOMESTICUS) FROM HATCH TO SEXUAL MATURITY
Authors: SHARP P. J.
Published: December 2008

Changes in plasma LH concentrations were followed in chickens of both sexes from hatch to sexual maturity using a radioimmunoassay. Mean levels of LH were lower in the females than in the males at all stages of development. These levels rose rapidly in both sexes during the first week after hatch to maxima of 6·5 ± 1·2 (s.e.m.) ng/ml (n = 6) in the males and 4·6 ± 0·6 ng/ml (n = 6) in the females. Thereafter levels of the hormone in the circulation stabilized in the males but fell over a period of 1 or 2 weeks in the females to 2·5–3 ng/ml.

Plasma LH levels started to rise steeply in both sexes when they were between 16 and 19 weeks old at the same time as there was an increase in the rate of comb growth. Afterwards in six of the males studied in detail the mean plasma LH level rose significantly (P < 0·01) over a period of 5–8 weeks from 8·1 ± 1·2 to 13·2 ± 1·9 ng/ml. In a parallel study on six females the rate of LH secretion increased for approximately 3 weeks and then decreased for about the same period forming a prepubertal LH peak. The first eggs were laid between 22 and 25 weeks of age when mean plasma LH levels had fallen to about 1·8 ng/ml. The mean plasma LH level in these hens when they were laying (1·8 ± 0·3 ng/ml) was significantly lower (P < 0·01) than when they were sexually immature (2·7 ± 0·3 ng/ml). The duration of the period of rapid comb growth in each bird was closely related in the males to the time during which prepubertal LH levels were rising rapidly, and in the females to the duration of the prepubertal LH peak.

Differences in mean plasma LH concentrations in individual birds of either sex before the onset of puberty appeared to be related to subsequent reproductive performance.
SPECIFIC RELEASE OF BOVINE NEUROPHYSIN II DURING ARTERIAL OR VENOUS HAEMORRHAGE IN THE COW
Authors: LEGROS J. J. , REYNAERT R. , PEETERS G.
Published: December 2008

An almost specific release of neurophysin II with only minor release of neurophysin I was found during venous or arterial haemorrhage in five cows. Our data confirm the results of experiments in vitro in which vasopressin has been found to be associated with neurophysin II within neurosecretory granules.
SEXUAL BEHAVIOUR IN CASTRATED RABBITS TREATED WITH TESTOSTERONE, OESTRADIOL, DIHYDROTESTOSTERONE OR OESTRADIOL IN COMBINATION WITH DIHYDROTESTOSTERONE
Authors: ÅGMO A. , SÖDERSTEN P.
Published: December 2008

Sexual behaviour and the function of the accessory sexual glands were studied in castrated rabbits injected with testosterone benzoate (TB), oestradiol benzoate (OEB), dihydrotestosterone benzoate (DHTB) or OEB in combination with DHTB. Testosterone benzoate (1 mg daily for 90 days) stimulated the sexual behaviour more than any of the other steroids. The combination of OEB (0·33 mg) and DHTB (1 mg) was no more effective than either of these steroids given alone. The function of the accessory sexual glands was stimulated to a level comparable to that of intact animals given TB. Dihydrotestosterone benzoate was, however, not very effective in this respect. Oestradiol benzoate alone or in combination with DHTB caused hypertrophy and very low secretory activity of the seminal vesicles. These results suggest that testosterone itself is active both in the brain and in the accessory sexual glands in rabbits. This is in contrast to the rat, in which aromatization to oestradiol in the brain and reduction to DHT in the periphery seems to be important.