bluuebunny/crossref_metadata_2025 huggingface dataset:
AN IMPROVED METHOD FOR THE SUPERFUSION OF DISPERSED RAT ADRENAL CELLS
Authors: McDOUGALL J. G. , WILLIAMS B. C.
Published: December 2008

Biophysical Endocrinology Unit, Department of Physics as Applied to Medicine, Middlesex Hospital Medical School, London, W1P 6DB

(Received 6 February 1978)

Steroid secretion by the zona glomerulosa is extremely sensitive to changes in the extracellular concentration of potassium ions ([K+]). The manner in which a change in [K+] is transmitted to the steroidogenic mechanism is not known, but recent data have shown that the flux of 45Ca2+ is altered during such stimulation (Mackie, Warren & Simpson, 1978). More detailed information concerning ion and hormone dynamics during stimulation may be obtained from studies involving the superfusion of dispersed cells.

The 'centrifuge' procedure (Schulster & Jenner, 1975) could not be applied successfully to zona glomerulosa cells; during the first 15 min 50% of the cells were lost, with a subsequent loss of 10% of the original number of cells/h. Thus the alternative 'cell-column' procedure (Lowry & McMartin, 1974) was evaluated and two
INHIBITORY ACTION OF HUMAN FOLLICULAR FLUID ON THE OVARIAN ACCUMULATION OF CYCLIC AMP
Authors: KRAIEM Z. , DRUKER B. , LUNENFELD B.
Published: December 2008

Institute of Endocrinology, Chaim Sheba Medical Center, Tel Hashomer, Israel

(Received 15 February 1978)

Porcine follicular fluid has been shown to inhibit the gonadotrophin-stimulated accumulation of cyclic AMP in vitro (Ledwitz-Rigby, Gay, Stetson, Young & Channing, 1977). The aim of the present investigation was to test for cyclic AMP inhibitory activity in human follicular fluid obtained during the periovulatory period.

Twelve normal, healthy subjects, aged 21-40 years, with regularovulatorycycles and requiring Iaparotomy for medical reasons, voluntarily consented to participate in the study. Laparotomy was scheduled as close as possible to the expected time of ovulation. With day 0 as the day of the operation, blood samples were taken daily on days −8 to −4 and three times/day on days −3 to 3 and the concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol-17β and progesterone in the plasma were determined by radioimmunoassay (Lunenfeld, Insler, Eshkol & Birnboim, 1974). During Iaparotomy,
ANNUAL VARIATIONS IN THE TOTAL LIPID AND PROTEIN CONTENT OF THE LIVER, FAT BODY, OVARY AND PLASMA OF THE FEMALE FROG (RANA ESCULENTA L.)
Authors: MILONE M. , IELA L. , ESPOSITO V. , RASTOGI R. K. , CHIEFFI G.
Published: December 2008

The concentrations of lipid and protein in the ovary, fat body, liver and plasma of the female frog (Rana esculenta L.) were found to exhibit marked seasonal variations. There was an interesting correspondence between the depletion of lipid in the plasma and fat body and an increased level of lipid in the ovary. It would appear that oestrogenic steroids stimulate and increase the concentrations of lipids in the plasma, whereas pituitary gonadotrophins influence the uptake of lipids by ovarian tissue for vitellogenesis.
EFFECT OF LUTEINIZING HORMONE ON THE LIPID COMPOSITION OF RAT OVARIES
Authors: SCHULER LINDA A. , FLICKINGER G. L. , STRAUSS J. F.
Published: December 2008

The lipid composition of immature rat ovaries was examined after induction of ovulation with pregnant mare serum gonadotrophin and human chorionic gonadotrophin and subsequent (7–8 days later) stimulation with 10 μg LH. Two hours after the administration of LH, there was a decrease of approximately 50% in the concentration of cholesteryl esters in the ovary. The percentages (by weight) of sterol esters containing stearate, linoleate, eicosatrienoate and arachidonate were reduced by LH treatment, whereas the percentage of the C24:4 acid increased. No changes were observed in either the concentrations or fatty acid composition of phospholipids and triglycerides. These observations suggest that the metabolism of cholesteryl esters is acutely affected by LH and that sterol esters bearing long-chain polyunsaturated fatty acids are preferentially mobilized. Liberation of these unsaturated fatty acyl moieties may have significant effects on metabolism in the ovarian cell.
ASSOCIATION BETWEEN 5-HYDROXYTRYPTAMINE RELEASE AND INSULIN SECRETION
Authors: GYLFE ERIK
Published: December 2008

The efflux of radioactivity after loading with trace amounts of tritiated 5-hydroxytryptamine ([3H]5-HT) or 5-hydroxytryptophan ([3H]5-HTP) was studied in perifused β-cellrich pancreatic islets from ob/ob mice. Analysis of the effluent revealed that more than 90% of the radioactivity was released as [3H]5-HT after loading with [3H]5-HTP. Increasing the concentration of glucose in the perifusion medium from 3 to 20 mmol/l enhanced the efflux when islets from fed mice were used and this effect was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Whereas 20 mm-glucose alone did not stimulate the efflux of 5-HT from islets isolated from mice starved for 3 days, a stimulatory effect was observed in the presence of IBMX. Stimulation of the efflux of radioactivity by glucose was inhibited if calcium was omitted from or adrenaline added to the medium. The results are consistent with the concept of exocytotic release of 5-HT occurring in response to stimulation of insulin secretion, although basal non-exocytotic transport must also be occurring across the β-cell membrane.
EFFECTS OF LOW CALCIUM AND LOW PHOSPHORUS DIETS ON THE DUODENAL ABSORPTION OF CALCIUM IN BETAMETHASONE-TREATED CHICKS
Authors: FOX J. , CARE A. D. , BLAHOS J.
Published: December 2008

The effect of oral administration of betamethasone (25 μg kg−1 day−1) on the duodenal absorption of calcium has been studied in chicks using the ligated loop technique in vivo. The chicks were fed normal calcium, normal phosphorus (NCaNP), low calcium, normal phosphorus (LCaNP) or normal calcium, low phosphorus (NCaLP) diets. Daily oral administration of betamethasone for 2–3 weeks markedly reduced the absorption of calcium in chicks fed the NCaNP diet, but did not significantly affect the adaptation in absorption when the NCaLP or LCaNP diets were fed for the same period of time. In one group of chicks, betamethasone was administered daily for 10 days before the birds were transferred to the NCaLP or LCaNP diets. Adaptation was again unaffected by betamethasone treatment. Administration of betamethasone caused a marked retardation in growth-rate, hypercalcaemia and an increased percentage of ash in the tibiae.
RELATIONSHIPS BETWEEN PROLACTIN AND FOLLICLE-STIMULATING HORMONE DURING EARLY PREGNANCY AND THE PUERPERIUM
Authors: KHATTAB T. Y. , JEQUIER ANNE M.
Published: December 2008

This investigation studies the relationship between the concentrations of prolactin and FSH in the serum during pregnancy and the puerperium. A single dose of 5 mg bromocriptine during early pregnancy induced a profound fall in the serum level of prolactin with a substantial rise 20 h later. During the initial reduction in the concentration of prolactin, no alteration was noted in the level of FSH but during the subsequent increase in the prolactin concentration, there was a significant (P<0·05) decrease in the concentration of FSH. During week 1 of the puerperium, the concentrations of FSH and prolactin were significantly lower in lactating women than in women who were not breast feeding, but there was no significant difference between the concentrations of FSH in women who had suppressed lactation with bromocriptine and in those whose lactation was suppressed by non-hormonal methods. When the concentration of FSH was measured every 10 min during a 30 min breast feed, there was a marked but short-lived rise in the serum concentration of prolactin but no change in the level of FSH. These results suggest that an increase in the serum level of prolactin in pregnancy can have a suppressive effect on the production of FSH. Although acute suckling-induced hyperprolactinaemia in the puerperium has no such effect, the maintenance of lactation in the long term does suppress the concentration of FSH in the serum.
FAILURE OF HISTAMINE TO INDUCE THE RELEASE OF LUTEINIZING HORMONE IN CASTRATED RATS PRIMED WITH SEX STEROIDS
Authors: DONOSO A. O. , BANZAN A. M.
Published: December 2008

Instituto de Investigaciones Cerebrales, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina

(Received 10 March 1978)

Injection of histamine into the third ventricle causes the release of luteinizing hormone (LH) in ovariectomized, steroid-primed and pro-oestrous rats (Donoso, Banzan & Borzino, 1976; Donoso, 1978). In oestrous rabbits, intraventricular injection of large doses of histamine or injection of histamine into the mediobasal hypothalamus induces ovulation and secretion of progesterone by the ovaries (Sawyer, 1955; Endröczi & Hilliard, 1965). However, histamine has no effect on the concentration of LH in the plasma of male rats (Donoso & Banzan, 1976). Together, these results suggest that histamine is able to induce the release of LH both before ovulation and in the presence of an adequate hormonal background.

The positive feedback effects of oestradiol and progesterone on the release of gonadotrophins are absent in male rats. Injection of oestradiol, progesterone or testosterone into steroid-primed
SIGNIFICANCE OF PROLACTIN IN SPONTANEOUSLY PERSISTENT OESTROUS RATS
Authors: GOSDEN R. G.
Published: December 2008

Department of Physiology, University Medical School, Teviot Place, Edinburgh, EH8 9AG

(Received 20 March 1978)

Ageing female rats maintained under standard laboratory lighting conditions (14 h light: 10 h darkness) frequently enter a state of persistent vaginal cornification because the pituitary gland fails to provide an ovulatory surge of gonadotrophic hormones. The ovaries of such animals become dominated by growing and cystic follicles as the corpora lutea disappear. The concentrations of prolactin in the pituitary gland and the circulation during persistent oestrus are known to be raised for at least part of the day (Clemens & Meites, 1971; Mallampati & Johnson, 1974; Shaar, Euker, Riegle & Meites, 1975; J. E. Beach, R. G. Gosden & J. W. Everett, unpublished observations). A possible antigonadotrophic role of prolactin in the aetiology of the persistent oestrous condition should be considered because of the known inverse relationship between the release of prolactin and gonadotrophins
CONCENTRATIONS OF OESTRADIOL-17β AND PROGESTERONE IN THE PERIPHERAL PLASMA OF THE CYNOMOLGUS MONKEY (MACACA FASCICULARIS) IN RELATION TO THE LENGTH OF THE MENSTRUAL CYCLE AND ITS COMPONENT PHASES
Authors: SHAIKH A. A. , NAQVI R. H. , SHAIKH S. A.
Published: December 2008

Ninety-three female cynomolgus monkeys were monitored throughout 647 menstrual cycles; 93·2% of these cycles were 22–37 days long and were normally distributed, with a mean of 29·2 days. Menstrual bleeding generally lasted for 3–5 days and was not related to the length of the cycle. The levels of progesterone and oestradiol-17β in the plasma were measured during the menstrual cycle in 30 monkeys. The concentration of oestradiol-17β reached a mid-cycle peak on day 11 or 12 of the cycle. The interval between the beginning of the cycle and the oestrogen peak was constant; the interval between the oestrogen peak and the end of the cycle increased or decreased with the cycle length. The level of progesterone began to rise at about the time of the oestrogen peak and remained raised for longer periods as the length of the cycle increased. The length of the menstrual cycle, therefore, appeared to be determined by the duration of the increase in the level of progesterone or by the life of the corpus luteum in the luteal phase. The relationship between the lengths of the cycle and the luteal phase can be defined by the expression: cycle length = 12·6+0·96 × length of luteal phase (correlation coefficient = 0·875).
EFFECTS OF PROSTAGLANDINS ON THE METABOLISM OF CHOLESTERYL ESTER IN RAT TESTES: CHANGES IN THE SYNTHESIS AND HYDROLYSIS OF CHOLESTERYL ESTER AND THE ACTIVITY OF CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME
Authors: TAKATORI T. , YAMAOKA A.
Published: December 2008

The effects of prostaglandins on testicular synthesis and hydrolysis of cholesteryl esters, the activity of the enzyme involved in cleavage of the cholesterol side-chain and on serum levels of testosterone and LH have been studied. Subcutaneous administration of prostaglandins to male rats caused an increase in the concentration of cholesteryl esters in the testes, a decrease in testicular synthesis and hydrolysis of cholesteryl esters but no change in the activity of the cholesterol side-chain cleavage enzyme. There was also a significant decrease in the serum level of testosterone, but the level of LH was raised. Prostaglandins also affected the fatty acid composition of lipids in rat testicular tissue; cholesteryl esters were found to contain greater amounts of arachidonic (C20:4) and docosapentaenoic (C22:5) acids. These findings suggest that prostaglandins are involved in the turnover of cholesteryl esters in rat testicular tissue and regulate the production of androgens.
INFLUENCE OF AUTONOMIC INNERVATION ON THE FOETAL RAT PANCREAS IN VITRO
Authors: DE GASPARO M. , KRINKE G. , MILNER G. R. , MILNER R. D. G.
Published: December 2008

Foetal rat pancreatic rudiments, explanted on day 14 of gestation and grown for 7 days in organ culture, were highly sensitive to the stimulatory effect of glucose on insulin secretion. The autonomic innervation of the cultivated explant was investigated as a possible explanation of this phenomenon. No sign of sympathetic innervation was detected in the pancreas explanted on day 14; the uptake of alpha-methyl-noradrenaline was not detectable by fluorescence microscopy, the concentration of noradrenaline/pancreatic rudiment was less than 7 pg and no nerve-endings containing granular vesicles were visible by electron microscopy. It was concluded that sympathetic innervation of the pancreas occurs after day 14 of gestation. Sympathetic receptors developed independently of innervation since phentolamine, and, to a lesser extent, phenoxybenzamine, potentiated the glucose-induced insulin release from cultured explants. The beta-agonists isoproterenol or salbutamol were inactive alone, but in combination with phentolamine, they potentiated the effect of glucose. Alpha-antagonists reversed the inhibitory effect of adrenaline in a dose-dependent manner. Intrapancreatic neurones were demonstrated microscopically as cholinesterase-positive cells; parasympathetic receptors were shown to be present after potentiation of glucose-stimulated insulin release by carbamylcholine and its reversal by atropine. The preservation of parasympathetic innervation and the absence of sympathetic innervation in the cultured pancreatic rudiment may explain in part the high sensitivity of the tissue to the stimulatory effect of glucose on the release of insulin.
EVIDENCE FOR PLEIOMORPHISM OF LUTEINIZING HORMONE IN PERIPUBERTAL FEMALE RATS
Authors: TER HAAR M. B. , WILSON CATHERINE A.
Published: December 2008

*A.R.C. Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT, and ‡Department of Physiology, Royal Veterinary College, London, NW1 OTU

(Received 28 March 1978)

Ovulation can be induced precociously in the prepubertal female rat by the administration of pregnant mare serum gonadotrophin (PMSG), provided that the animal weighs over 60 g (Wilson, Endersby & McDonald, 1974). The hormonal changes brought about by this treatment have been studied (J. C. Buckingham, M. B. ter Haar, A. S. McNeilly & C. A. Wilson, data to be published) and it has been found that the preovulatory concentrations of radioimmunoassayable luteinizing hormone (LH) varied according to the antiserum used. These findings are described in the present communication.

Female Sprague–Dawley rats (Tuck & Sons, Rayleigh, Essex) were brought into the department on day 21 of life, kept under conditions of controlled lighting (lights on 05.00–19.00 h) and provided with pelleted rat diet (No. 86, Dixon &
PLASMA CONCENTRATIONS OF LUTEINIZING HORMONE, TESTOSTERONE AND ANDROSTENEDIONE IN CASTRATED AND ADRENALECTOMIZED BULL CALVES
Authors: BASS J. J. , PETERSON A. J. , PAYNE E.
Published: December 2008

Ministry of Agriculture and Fisheries, Research Division, Ruakura Agricultural Research Centre, Hamilton, New Zealand

(Received 17 April 1978)

An increase in the plasma concentration of luteinizing hormone (LH) occurs in response to castration in bull calves aged 1–4 months; this response is of similar magnitude to that seen in cattle castrated as adults (Odell, Hescox & Kiddy, 1970). In bull calves castrated at birth, however, there is no increase in the plasma concentration of LH until after 28 days of age (Bass, Peterson, Payne & Jarnet, 1977). In other species a range of responses to castration has been reported. Gonadectomy of male guinea-pigs 0–35 days after birth produces an increase in the plasma concentration of LH similar to that observed in guineapigs castrated as adults (Donovan, ter Haar, Lockhart, MacKinnon, Mattock & Peddie, 1975). In contrast, the castration of young male macaques does not cause an immediate increase in the
PLASMA CONCENTRATIONS OF 25-HYDROXY VITAMIN D IN PREGNANT AND LACTATING EWES AND FOETAL AND NEWBORN LAMBS
Authors: BARLET J.-P. , ARGEMI B. , DAVICCO MARIE-JEANNE , LEFAIVRE J.
Published: December 2008

I.N.R.A., Theix, 63110 Beaumont, France and Groupe Hospitalier de la Timone, 13385 Marseille, France

(Received 31 May 1978)

Very little information is available concerning interrelationships between maternal and foetal concentrations of 25-hydroxy vitamin D3 (25-OHD3; Hillman & Haddad, 1974; Ross, Care, Pickard, Peacock & Robinson, 1976; Weisman, Sapir, Harell & Edelstein, 1976). This paper describes the concentrations of 25-OHD3 in the plasma of pregnant and lactating ewes and their foetal and newborn lambs.

Five ewes bearing single lambs were selected by radiography performed on day 100 of gestation in winter. The daily intakes of calcium, phosphate and magnesium for each animal were respectively, 11, 7 and 2 g. From day 26 pre partum until day 4 post partum, blood samples were collected through catheters implanted on day 115 of gestation in the left foetal and maternal carotid arteries (Mellor & Matheson, 1975). Plasma concentrations of 25-OHD3
HORMONAL REGULATION OF 5α-REDUCTASE ACTIVITY IN RAT EPIDIDYMIS
Authors: DE LARMINAT MARÍA ANA , MONSALVE A. , CHARREAU E. H. , CALANDRA R. S. , BLAQUIER J. A.
Published: December 2008

The specific activity of epididymal 5α-reductase (pmol 5α-reduced products mg protein−1 h−1) decreased by 17, 44, 58 and 83% of the initial value and its total activity (nmol 5α-reduced products organ−1 h−1) decreased by 66, 85, 94 and 98% 2, 4, 8 and 14 days respectively, after castration. The loss of total activity always exceeded the decrease in organ weight and protein content. The decline in enzymic activity could be prevented by implantation of testosterone at the time of castration. Administration of testosterone propionate (200 μg/day) for 12 days starting 1 month after castration was associated with the weights of the accessory organs returning to the control values and although the specific activity of 5α-reductase was almost completely restored by this treatment, the total activity of the nuclear fraction remained at 49% of the control value. Recombination experiments demonstrated that the effect of androgens is not mediated by a factor present in the soluble fraction and the concomitant administration of androgen and either cycloheximide or actinomycin D blocked the effect of androgen. These data suggest that androgens stimulate the synthesis of epididymal 5α-reductase.
DIURNAL VARIATIONS IN THE INFLUENCE OF THE ULTIMOBRANCHIAL GLANDS ON CALCIUM HOMEOSTASIS IN THE FROG (RANA PIPIENS)
Authors: ROBERTSON D. R.
Published: December 2008

The effect of the light–darkness cycle on the efficiency of the ultimobranchial and parathyroid glands in altering duodenal calcium transport and plasma and urinary concentrations of calcium was examined in the adult male frog (Rana pipiens). Frogs were unfed, but were allowed access to 0·05 m-CaCl2 in the surrounding medium after ultimobranchialectomy or parathyroidectomy. Calcium transport, as assayed by the everted gut-sac technique, was increased in ultimobranchialectomized frogs at sunrise, concomitant with acute hypercalcaemia and hypercalciuria. An opposite but chronic response was observed in parathyroidectomized frogs with intact ultimobranchial glands. The maximum response observed at sunrise occurred when the concentration of calcium in the plasma of control frogs was decreasing; the minimum response, which occurred 6 h after sunrise, was coincident with a diurnal peak in the concentration of calcium. Vitamin D3 (500 μg/frog) enhanced calcium transport in ultimobranchialectomized frogs, which resulted in chronic hypercalcaemia and hypercalciuria. The results suggest that diurnal variations in the plasma concentration of calcium do not initiate ultimobranchial activity, but are a response to endocrine control synchronized with the transition from darkness to light.
TRANSFER OF MILK PROLACTIN TO THE PLASMA OF NEONATAL RATS BY INTESTINAL ABSORPTION
Authors: WHITWORTH N. S. , GROSVENOR C. E.
Published: December 2008

Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. 131I-Labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with 131I-labelled rat prolactin and after the pups had received 131I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the 131I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10·5 or 21·0 μg B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46·2 μg B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13- to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of offspring suckled by mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn rat is permeable to prolactin and that milk may constitute an exogenous source of prolactin for the suckled offspring.
EFFECT OF CORTICOTROPHIN ON CORTISOL SECRETION IN CASTRATED RHESUS MONKEYS
Authors: FARVER C. F. , DE WIED D. , TOIVOLA P. T. K.
Published: December 2008

Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53706, U.S.A.

(Received 22 May 1978)

In a wide variety of species corticotrophin (ACTH) is known to stimulate the synthesis and secretion of adrenocortical steroids. Studies with rhesus monkeys have shown that these responses can be affected by a number of factors including the method of handling and the type of physical restraint (Mason, 1959). In addition, androgens may depress plasma levels of glucocorticoids in primates (Brown & Migeon, 1956; Huis in't Veld, Louwerens & van den Spek, 1960). It was therefore decided to study the response of plasma cortisol to ACTH without these neural or hormonal influences. This report describes the effects of ACTH on castrated rhesus monkeys adapted to chronic restraint.

Four chair-restrained, orchidectomized rhesus monkeys (Macaca mulatta) bearing chronic indwelling venous catheters were used as experimental subjects and were housed, maintained and subjected to blood sampling as
RADIOIMMUNOASSAY OF ARGININE-VASOPRESSIN IN HUMAN URINE AND ITS USE IN PHYSIOLOGICAL AND PATHOLOGICAL STATES
Authors: KHOKHAR A. M. , RAMAGE CHRISTINE M. , SLATER J. D. H.
Published: December 2008

A highly specific radioimmunoassay for arginine-vasopressin (AVP) in human urine has been developed, with a detection limit of 2·2 fmol/ml. The mean recovery of added AVP was 99·5 ± 3·1 (s.d.)% when correction was made for the fact that an inverse relationship was observed between the recovery of AVP and the osmolality of the urine. The intraand interassay coefficients of variation were 3·5–7 and 2·5–10% respectively. Arginine-vasopressin remains stable in urine after repeated freezing and thawing after storage at 4 or 20 °C for up to 7 days and at − 20 °C for more than 3 months. During unrestricted fluid intake in normal people, the mean rate of renal excretion of AVP was 95 ± 68 (s.d.) fmol/min. An isosmotic reduction of 9% in the plasma volume increased the excretion of AVP to 259 ± 147 (s.d.) fmol/min. At the height of water-induced diuresis the rate of excretion fell to 70 ± 28 (s.d.) fmol/min. Fluid deprivation for 18 h produced a moderate but significant increase in mean excretion of AVP, to a value of 116 ± 67 (s.d.) fmol/min. Patients with compulsive water drinking showed a normal relationship between urine osmolality and the rate of excretion of AVP. In pituitary diabetes insipidus, AVP was undetectable, whereas in hereditary nephrogenic diabetes insipidus a progressive increase in the rate of excretion of AVP was observed in response to dehydration. There was a wide variation in the rate of excretion of AVP (range 126–8704 fmol/min) in patients with unexplained hyponatraemia, presumed to be due to an inappropriate secretion of antidiuretic hormone. Despite this variation, the relationship between urine osmolality and the rate of excretion of AVP clearly differed from that observed in normal people.
UTILIZATION OF [26-14C]CHOLESTEROL BY HUMAN FOETAL ADRENAL GLANDS IN VITRO
Authors: GUNASEGARAM R. , PEH K. L. , CHEW P. C. T. , KARIM S. M. M. , RATNAM S. S.
Published: December 2008

Department of Obstetrics and Gynaecology, University of Singapore, Kandang Kerbau Hospitalfor Women, Singapore 8, Republic of Singapore

(Received 3 May 1978)

From the previous studies of Bloch & Benirschke (1959, 1962) and Plotz, Kabara, Davis, LeRoy & Gould (1968) it appears that at mid-term, human foetal adrenal glands are capable of synthesizing C21- and C19-steroids de novo from acetate and cholesterol. Villee, Engel, Loring & Villee (1961), however, incubated slices and homogenates of foetal adrenal gland with [2-14C]acetate or [4-14C]cholesterol and could not demonstrate the incorporation of radioactivity into these steroids. Moreover, perfusion studies by three groups of investigators indicated only minute conversions of the same radioactive substrates into neutral steroids in the foetal adrenal glands (Solomon, Bird, Ling, Iwamiya & Young, 1967; Telegdy, Weeks, Archer, Wiqvist & Diczfalusy, 1970a; Telegdy, Weeks, Lerner, Stakemann & Diczfalusy, 1970b). It is widely believed that steroid hormones are normally synthesized from acetate via
UTERINE TISSUES FROM PREGNANT GOATS PRODUCE 6-OXO-PROSTAGLANDIN F1α IN VITRO
Authors: MITCHELL M. D. , FLINT A. P. F. , HICKS B. R. , KINGSTON E. J. , THORBURN G. D. , ROBINSON J. S.
Published: December 2008

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU

(Received 21 July 1978)

It now seems likely that prostaglandins play an important role in the mechanisms of parturition in many species (Flint & Hillier, 1976; Thorburn, Challis & Robinson, 1977), including the goat (Thorburn, Nicol, Bassett, Shutt & Cox, 1972; Currie & Thorburn, 1977). This evidence has been further strengthened by the demonstration of the production of prostaglandins in vitro by uterine tissues from goats during late pregnancy (Mitchell, Flint, Robinson & Thorburn, 1978b). The recent discovery of prostacyclin (Moncada, Gryglewski, Bunting & Vane, 1976) has added a new dimension to prostaglandin research since in some biological systems it has a greater potency than other prostaglandins (Moncada et al. 1976; Omini, Moncada & Vane, 1977). Prostacyclin is highly unstable in aqueous media and degrades spontaneously to 6-oxo-prostaglandin F1α (6-oxo-PGF1α; Johnson, Morton, Kinner, Gorman,
HIGHLY SPECIFIC BINDING OF 1,25-DIHYDROXYCHOLECALCIFEROL IN BONE CYTOSOL
Authors: MANOLAGAS S. C. , TAYLOR C. M. , ANDERSON D. C.
Published: December 2008

A method developed initially for the detection of high-affinity binding of glucocorticoids in the cytosol from foetal rat calvaria has been adapted for metabolites of vitamin D. Consistent displacement of [3H]1,25-dihydroxycholecalciferol ([3H]1,25(OH)2D3) by unlabelled 1,25(OH)2D3 was obtained with an apparent dissociation constant (Kd) of 2·3 × 10−9 mol/l. The specificity of this binding was examined by competition experiments. Displacement of labelled 1,25(OH)2D3 by a 100-fold excess of unlabelled metabolites, expressing the fall with unlabelled 1,25(OH)2D3 as 100%, was as follows: 25-hydroxycholecalciferol (25(OH)D3), 61%; 24,25-dihydroxycholecalciferol, 29%; cholecalciferol, 3%. These are similar to results for the chick mucosa nuclear 1,25(OH)2D3 receptor. No displacement was obtained with corticosterone, testosterone, oestradiol or progesterone. When [3H]25(OH)D3 was used as ligand, a displacement curve with unlabelled 25(OH)D3 indicated only binding with a greater Kd (approximately 10−7 mol/l). These data suggest a direct action of 1,25(OH)2D3 on bone which is similar to that of steroid hormones on their target tissues.
VARIATIONS IN CONCENTRATIONS OF PROLACTIN, LUTEINIZING HORMONE, GROWTH HORMONE AND PROGESTERONE IN THE PLASMA OF BROODY BANTAMS (GALLUS DOMESTICUS)
Authors: SHARP P. J. , SCANES C. G. , WILLIAMS J. B. , HARVEY S. , CHADWICK A.
Published: December 2008

The concentrations of prolactin, LH, progesterone and GH were measured in the blood of broody bantam hens. The concentration of prolactin was at its highest when the birds began to incubate their eggs and in six out of nine hens it tended to remain raised until the eggs hatched. The increase in the concentration of prolactin was small: in incubating hens it was only 23% higher than in hens caring for their young and 14% higher than in laying hens (P < 0·05 for both comparisons). The concentration of GH tended to be depressed in hens caring for young but otherwise was not related to reproductive activity. The concentrations of LH and progesterone decreased at the onset of incubation and remained depressed while the hens sat on their eggs (P < 0·001 for both comparisons). After the chicks hatched, the level of LH began to increase slowly whereas the level of progesterone remained low. The hens stopped showing broody behaviour between 4 and 10 weeks after the chicks had hatched; this corresponded to the time when the concentration of LH had increased to values found in laying hens.

These observations provide some evidence that prolactin secretion increases at the onset of incubation and support the view that the hormone is not secreted at an increased rate while hens are caring for their young.
ACETYLCHOLINE STIMULATES GROWTH HORMONE SECRETION, PHOSPHATIDYL INOSITOL LABELLING, 45Ca2+ EFFLUX AND CYCLIC GMP ACCUMULATION IN BOVINE ANTERIOR PITUITARY GLANDS
Authors: YOUNG P. W. , BICKNELL R. J. , SCHOFIELD J. G.
Published: December 2008

Acetylcholine (25 μmol/l) in the presence of the choline esterase inhibitor physostigmine (67 μmol/l) increased the release of growth hormone and efflux of 45Ca2+ from perifused bovine pituitary slices; the time taken for the maximal response to occur was the same. In batch incubations, acetylcholine (1 μmol/l–1 mmol/l) increased pituitary cyclic GMP concentrations in the pituitary gland within 2 min, and increased incorporation of [3H]inositol and [32P]phosphate into pituitary phosphatidyl inositol within 15 min. Cyclic AMP concentrations were not significantly changed 2 or 5 min after acetylcholine addition. All the tissue responses were inhibited by prior exposure of the tissue to atropine (1 μmol/l) but not by tubocurarine (10 μmol/l–1 mmol/l), indicating that the responses were mediated by receptors of the muscarinic type. The similarities between these responses and those to known hypothalamic hypophysiotrophic hormones are discussed.
EVIDENCE THAT BOTH LONG-ACTING THYROID STIMULATOR AND LONG-ACTING THYROID STIMULATOR-PROTECTOR STIMULATE THE HUMAN THYROID GLAND
Authors: HOLMES S. D. , DIRMIKIS S. M. , MARTIN T. J. , MUNRO D. S.
Published: December 2008

Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay.

The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS–IgG; LATS-P–IgG was inactive. In contrast, both LATS–IgG and LATS-P–IgG were equally effective in slices of human thyroid.
EFFECTS OF CYPROTERONE AND CYPROTERONE ACETATE ON THE ADRENAL GLAND IN THE RAT: STUDIES IN VIVO AND IN VITRO
Authors: PANESAR N. S. , HERRIES D. G. , STITCH S. R.
Published: December 2008

Male Wistar rats were treated for three weeks with cyproterone (1·7 or 5·1 mg/day) or cyproterone acetate (2 or 6 mg/day). The adrenal weights of animals treated with either dose of cyproterone acetate were significantly less (P < 0·001) than those of untreated animals. In contrast, the adrenal weights of animals treated with cyproterone did not differ from those of the controls. The concentrations of corticosterone in the plasma were significantly less (P < 0·001) in both groups treated with cyproterone acetate compared with those of the controls; only the higher dose of cyproterone reduced the plasma concentration of corticosterone (P < 0·001).

Cyproterone acetate inhibited the rat adrenal 3β-hydroxysteroid dehydrogenase–5-ene,4-ene-isomerase complex in vitro, with both pregnenolone and dehydroepiandrosterone as substrates. Analysis of the reaction rates suggested an uncompetitive mode of inhibition.

These results suggest that in rats the antiandrogens cyproterone and cyproterone acetate may provoke adrenal insufficiency by inhibition of steroid biosynthesis. Furthermore, indirect evidence from the mass and morphology of the adrenal suggests that cyproterone acetate may also suppress production or secretion of ACTH by the pituitary gland.
ONTOGENY AND CONTROL OF PROLACTIN RECEPTORS IN THE MAMMARY GLAND AND LIVER OF VIRGIN, PREGNANT AND LACTATING RATS
Authors: HAYDEN T. J. , BONNEY ROSEMARY C. , FORSYTH ISABEL A.
Published: December 2008

Prolactin receptors were identified and partially characterized in the mammary gland of the rat. The binding of 125I-labelled ovine prolactin to a subcellular particulate fraction of rat mammary gland decreased between days 30 and 100 of age. Over the same period, binding to the liver increased and there was a significant negative correlation between prolactin binding in the two tissues. Binding to the mammary gland was low during pregnancy, increased in early lactation and declined after the litters were weaned. Binding to the liver was lower during lactation than during pregnancy or the period after weaning suggesting that tissue-specific factors may operate in the control of this receptor. In virgin rats, prolactin binding by the mammary gland was increased by oestrogen. This effect was blocked by hypophysectomy and partially restored by replacement therapy with prolactin. Hypothyroidism and treatment with progesterone also reduced the response to oestrogen. The maintenance of prolactin binding by the mammary gland of lactating rats depends on the presence of the ovaries and pituitary, thyroid and adrenal glands. Examination of the ratio epithelium: stroma suggests that prolactin acts by increasing the number of epithelial cells in the mammary gland and that thyroid, adrenal and ovarian hormones modulate the number of receptors per cell.
INCREASED RATIO OF 5α-REDUCTASE: 3α(β)-HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE HYPERPLASTIC HUMAN PROSTATE
Authors: BRUCHOVSKY NICHOLAS , LIESKOVSKY GARY
Published: December 2008

The activities of 5α-reductase and 3α(β)-hydroxysteroid dehydrogenase were assayed in homogenates of eight normal, 21 hyperplastic and four carcinomatous human prostates. Samples consisting of 300–500 μg tissue protein in Tris buffer, pH 7·0, were incubated at 37 °C for 30 min in the presence of 50 nm-[3H]androgen and an NADPH-generating system started with 5 × 10−4 m-NADP. The yield of 5α- and 3α-reduced metabolites, as established by using t.l.c. and g.l.c., gave an estimate of enzyme activity. The formation of metabolites denoting 5α-reductase activity in normal, hyperplastic and carcinomatous tissue respectively was 28·8 ± 47 (s.e.m.), 76·8 ± 8·9 and 3·5 ± 0·7 pmol 30 min−1 mg protein−1; similarly, that denoting 3α(β)-hydroxysteroid dehydrogenase activity was 69·3 ± 6·7, 46·6 ± 5·7 and 38·8 ± 22·1 pmol 30 min−1 mg protein−1. In all normal prostates 5α-reductase activity was lower than 3α(β)-hydroxysteroid dehydrogenase activity. Conversely, in 18 out of 21 hyperplastic prostates, 5α-reductase activity was higher than 3α(β)-hydroxysteroid dehydrogenase activity. The effect of the increase in 5α-reductase activity without a compensatory change in 3α(β)-hydroxysteroid dehydrogenase activity was to alter the mean ratio between 5α-reductase and 3α(β)-hydroxysteroid dehydrogenase activities from 0·47 ± 0·11 in the normal prostate to 1·84 ± 0·19 in hyperplastic tissue. It is inferred that this change may predispose the hyperplastic prostate to asymmetrical rates of androgen metabolism and thereby contribute to the abnormal accumulation of dihydrotestosterone.
SEPARATE ROLES OF ANDROGEN AND OESTROGEN IN THE MANIPULATION OF GROWTH AND EFFICIENCY OF FOOD UTILIZATION IN FEMALE RATS
Authors: PERRY B. N. , McCRACKEN A. , FURR B. J. A. , MACFIE H. J. H.
Published: December 2008

The roles of androgen and oestrogen in the perinatal and postpubertal stages of developmen on the masculinization of female patterns of growth have been investigated in several experi ments in rats.

A stimulatory effect of testosterone on subsequent growth and efficiency of food utilization was only observed when administered perinatally to intact females as the propionate ester. Thus females which were untreated (or androgenized) perinatally and ovariectomized at weaning failed to grow more rapidly or utilize food more efficiently when treated with mixed testosterone esters from 36 to 38 days of age. Also autoimmunity to luteinizing hormone releasing hormone (LH-RH) had little effect on the growth or efficiency of food utilization of male rats, although testicular development was grossly affected.

An inhibitory effect of oestrogen on subsequent growth and efficiency of food utilization was demonstrated by surgical ovariectomy and by autoimmunity to LH-RH. Also perinatal administration of oestradiol benzoate to intact female rats depressed growth below that of untreated intact litter-mate females until about 50 days of age. Then oestradiol benzoate-treated female rats grew to a larger size than untreated intact litter-mates but not to a heavier weight than untreated litter-mate females which like the oestradiol benzoate-treated females, were ovariectomized at 18–21 days of age. Both of these groups of female rats differed markedly in weight gain from females which were perinatally androgenized and ovariectomized at weaning. The effects of androgenization and ovariectomy on weight gain were comparable and additive in female rats fed restrictedly or ad libitum.

Nevertheless, androgenized + ovariectomized female rats fed restrictedly or ad libitum failed to grow as rapidly as male rats. Some additional factor(s) prevents complete masculinization of the female pattern of development. The stimulatory effects of androgenization and ovariectomy on the growth of females appear to be related to endocrine mechanisms controlling the onset of pubertal changes in somatic development.
ELECTROCHEMICAL DEPOSITION OF IRON ONTO RAT OXYTOCINERGIC NEURONES DOES NOT RESULT IN MILK-EJECTION
Authors: DYER R. G.
Published: December 2008

Exposure of the preoptic-tuberoinfundibular system to iron ions causes ovulation in the pro-oestrous rat. This electrochemical treatment has been used frequently to study the way that the hypothalamus triggers secretion of gonadotrophic hormone and most investigators have assumed that the effect is mediated by the direct excitation of those neurones exposed to the cation. The present paper reports experiments designed to confirm that iron directly excites hypothalamic neurones to the firing frequencies essential for ovulation.

Because of the difficulty of measuring input–output relationships in the diffuse preoptic-tuberoinfundibular system the experiments were performed on the anatomically distinct oxytocinergic neurones of the paraventricular-hypophysial tract in lactating rats. These neurones were stimulated electrically (from 10 to 50 Hz for between 1 and 300 s) and subjected to the electrochemical treatment by depositing iron ions from the tip of the stimulating electrode (up to 250 μA anodal current for between 60 and 180 s). Changes in intramammary pressure were used to indicate oxytocin release and mammary glands were calibrated for sensitivity by intravenous injection of oxytocin.

Electrical stimulation in excess of about 15 Hz invariably caused release of sufficient oxytocin to cause a rise in intramammary pressure. In contrast, no changes in pressure were observed during or after the electrochemical deposition of iron. The results suggest that the response of hypothalamic neurones to electrochemical treatment is not the same as their response to electrical stimulation.
PURIFICATION OF THE CYTOPLASMIC OESTROGEN RECEPTOR FROM MAMMARY TUMOURS INDUCED IN RATS WITH DIMETHYLBENZANTHRACENE
Authors: AL-NUAIMI N. , DAVIES P. , GRIFFITHS K.
Published: December 2008

The oestrogen receptor from mammary tumours induced in rats by dimethylbenz(a)-anthracene has been extensively purified by affinity chromatography and isoelectric focusing. The unpurified cytoplasmic 8 S oestrogen receptor had a molecular weight of 240 000, a Stokes radius of 5·4 nm and a frictional ratio of 1·32; the Km (dissociation constant) at 4 °C for [3H]oestradiol-17β was 0·184 nmol/l. At the end of affinity chromatography the molecular weight was still 240 000 but under the conditions of isoelectric focusing it was reduced to 110 000, with a Stokes radius of 4·0 nm, a frictional ratio of 1·26 and an isoelectric point of 6·4.
COMPARISON OF PROLACTIN LEVELS IN HUMAN SEMEN AND SEMINAL PLASMA
Authors: LUQMAN W. A. , MATEJ L. A. , SMITH M. L.
Published: December 2008

Semen samples were collected from 35 men and the levels of prolactin in semen and seminal plasma were measured. There was no significant difference in prolactin concentrations between the two fluids (t = 0·333, P > 0·7). There was also no correlation between the prolactin concentration and the kinematic viscosity of the semen (r = 0·065, P > 0·7).
SPECIFICITY OF RADIOIMMUNOASSAYS FOR RELAXIN
Authors: BRYANT-GREENWOOD GILLIAN D. , GREENWOOD F. C.
Published: December 2008

The specificities of two radioimmunoassays (RIA) for relaxin, based upon crude porcine relaxin (NIH-R-P1; RIA I) and a highly purified porcine relaxin (RIA II) have been studied concurrently using purified hormones and plasma samples. A labelled fraction, selected from radio-iodinated NIH-R-P1 and used in that RIA, was also bound to antiserum raised to the highly purified relaxin. Hence a third RIA was possible in which both the crude and the purified relaxins inhibited in the ng/ml range. Porcine insulin and the connecting peptide of porcine proinsulin did not inhibit any of the assay systems whereas porcine proinsulin did inhibit in each assay at the μg/ml range. Concurrent measurements by assays I and II have been made in sheep plasma obtained during both delivery of the lamb and suckling. The peak values obtained by assays I and II are 3 and 6 min out of phase during suckling and delivery respectively; the NIH-R-P1 relaxin immunoactivity appearing first. The plasma inhibition curves of both appear to be the sum of individual contributions from relaxin and relaxin-like peptides, such as prorelaxin and its fragments, as seen by different antisera. Both assays, however, give qualitatively similar indices of relaxin immunoactivity. The RIA developed for the more purified peptide would be expected to yield a better quantitative estimate of relaxin secretion but this, like specificity, cannot be shown absolutely.
SERUM LEVELS OF THE ACID-ETHANOL SOLUBLE COMPONENT OF NON-SUPPRESSIBLE INSULIN-LIKE ACTIVITY IN UNTREATED AND TREATED STREPTOZOTOCIN-DIABETIC RATS
Authors: FRANKLIN R. C. , RENNIE G. C. , CAMERON D. P.
Published: December 2008

Streptozotocin-diabetic rats suffered growth failure and had reduced serum levels of the acid–ethanol soluble component of non-suppressible insulin-like activity (NSILA-S) compared with normal rats. Chronic insulin substitution (6 weeks) resulted in a normalization of serum levels of NSILA-S; this was accompanied by a normal increase in weight. Insulin therapy for 3 days resulted in a partial recovery of serum levels of NSILA-S and a slight but significant accompanying gain in weight. Short-term administration of GH also resulted in a partial recovery of the serum level of NSILA-S, in spite of continued uncontrolled diabetes.

These results demonstrate that, in the rat, insulin as well as GH contributes to the regulation of serum levels of NSILA-S.
FOETAL-MATERNAL PRODUCTION AND TRANSFER OF CORTISOL DURING THE LAST DAYS OF GESTATION IN THE GUINEA-PIG
Authors: DALLE M. , DELOST P.
Published: December 2008

The metabolism and the rate of transfer of cortisol across the placenta in pregnant guinea-pigs and foetuses were studied by constant intravenous infusions of tritium-labelled cortisol. Estimates of endogenous and radioactive plasma cortisol levels were used to calculate the following parameters at four stages before parturition (days 62, 64, 66 and 67; parturition occurring at day 68): metabolic clearance rate; production rate; adrenal secretory rate; transfer rate from mother to foetus and from foetus to mother; irreversible removal rate; the fraction of cortisol derived from the other in the foetal and maternal vascular compartments; the fraction of secreted and recycled cortisol involved in the transfer. The metabolic clearance rate and the rates of production and secretion of cortisol were higher in the mother than in the foetus between days 62 and 67 of gestation. About 90% of the foetal cortisol was of maternal origin. The fraction of maternal cortisol of foetal origin increased in the last days of gestation.
GLUCOCORTICOID AND MINERALOCORTICOID PATHWAYS IN TWO ADRENOCORTICAL CARCINOMAS: COMPARISON OF THE EFFECTS OF o,p′-DICHLORODIPHENYLDICHLOROETHANE, AMINOGLUTETHIMIDE AND 2-p-AMINOPHENYL-2-PHENYLETHYLAMINE IN VITRO
Authors: TOUITOU YVAN , BOGDAN ANDRÉ , AUZEBY ANDRÉ , DOMMERGUES JEAN-PAUL
Published: December 2008

The synthesis of glucocorticoids and mineralocorticoids in vitro was studied in an adrenocortical carcinoma after ablation from an 11·5-year-old boy. This patient had been unsuccessfully treated with high doses of o,p′-dichlorodiphenyldichloroethane (o,p′-DDD) and aminoglutethimide. These in-vitro results were compared with those obtained with another adrenocortical carcinoma removed from a 26-year-old woman who had received no preoperative treatment. The sensitivity of these adrenocortical carcinomas to o,p′-DDD, aminoglutethimide and 2-(p-aminophenyl)-2-phenylethylamine (SKF 12185) was investigated. Synthesis of cortisol (47%) and corticosterone (45%) in control incubations showed that 11β-hydroxylase activity was not affected by the treatment. This explains the raised level of plasma cortisol in the treated child. All three compounds inhibited both 11β-hydroxylase and 18-hydroxylase activities up to 95%, depending on the inhibitor. This study shows (a) an inhibitory effect of o,p′-DDD on the steroidogenesis of an adrenocortical carcinoma in vitro, an effect not previously reported in man or laboratory animals, and (b) the in-vitro efficacy of o,p′-DDD and aminoglutethimide on corticosteroidogenesis by a carcinoma unresponsive to treatment in vivo. This discrepancy between data obtained in vivo and in vitro could possibly be explained by either an insufficient ratio of ingested dose: tumour mass, or a malabsorption of the drugs in this patient.