bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF PERINATAL OESTROGEN ON THE PRETREATMENT REQUIRED FOR MOUSE MAMMARY LOBULAR FORMATION IN VITRO
Authors: WARNER M. R.
Published: December 2008

Morphological differentiation was enhanced in mammary glands from mice injected with oestradiol as neonates both in vivo, after 9 days of pretreatment with oestrogen and progesterone, and in vitro, either after 6 or 9 days of pretreatment and on all hormone supplements, or after culture with oestradiol, progesterone, aldosterone, insulin and thyroxine with or without prolactin and growth hormone. These hormone combinations further enhanced development, whereas culture with insulin and thyroxine did not.

Differentiation in vitro was least on medium containing insulin + thyroxine, and was greatest on the complete medium (insulin, thyroxine, growth hormone, prolactin, aldosterone, progesterone and oestradiol). An intermediate degree of differentiation occurred when growth hormone and prolactin were omitted from the complete medium.

Differences in lobule formation between oestrogen-treated and control mice were probably ovary-dependent at the dose used (25 μg/day), since pretreatment with oestradiol and progesterone was necessary to reveal them.

Enhanced hormone sensitivity of murine mammary tissues exposed to oestradiol early in life may be related to subsequent enhanced dysplastic potential of the tissue and provides a further basis for caution in the administration of steroids to immature individuals.
STIMULATORY AND INHIBITORY EFFECTS OF OVARIAN STEROIDS ON GONADOTROPHIN SECRETION IN OVARIECTOMIZED RATS AFTER ANTERIOR HYPOTHALAMIC DEAFFERENTATION
Authors: TALEISNIK S. , CALIGARIS L. , BELTRAMINO C. , CÁCERES A.
Published: December 2008

The effect of frontal hypothalamic deafferentation on the release of LH and FSH was studied in ovariectomized rats. Frontal cuts were placed just in front of the arcuate nucleus, at the posterior border of the optic chiasma (RCS), at the level of the anterior commissure (POS) and in front of the optic chiasma (PCS). Animals with RCS and POS cuts showed vaginal smears with persistent cornification; the other groups had irregular cycles.

The concentrations of LH and FSH in the serum increased after ovariectomy in deafferentated animals, but after 4 weeks the levels were lower than in the animals without hypothalamic lesions except for the PCS group. The more caudally that the cuts were located, the lower were the concentrations of hormones in the serum. The injection of repeated doses of oestradiol benzoate resulted in a decrease in serum gonadotrophin of both rats without hypothalamic lesions and RCS rats. Although a greater decrease was observed in the lesioned than in the intact rats, it is believed that such an effect does not indicate an increased sensitivity of deafferentated animals to this steroid.

The stimulatory effect of progesterone on LH and FSH release was studied in ovariectomized rats primed with oestradiol benzoate. The responses were unchanged in PCS animals but failed to occur in POS and RCS rats. Measurement of the level of gonadotrophin-releasing hormone in frontal hypothalamic slices from RCS animals showed a decreased level behind the cut and an increased one in front of it, suggesting that perikarya located in front of the section were sending their axons to the mediobasal hypothalamus. It is believed that the blockade of the stimulatory effect on gonadotrophins by frontal hypothalamic deafferentation is due to the transection of these axons. Cuts placed immediately in front of the arcuate nucleus, however, permitted progesterone-induced gonadotrophin release because of incoming neurones containing gonadotrophin-releasing hormone, which end in structures immediately rostral to the cut. The results indicate that effects of both inhibitory and stimulatory ovarian steroid feedback are impaired by frontal hypothalamic deafferentation.
EARLY FATE OF SOMATOSTATIN IN THE CIRCULATION OF THE RAT AFTER INTRAVENOUS INJECTION
Authors: McMARTIN C. , PURDON GILLIAN E.
Published: December 2008

The products of somatostatin in the circulation have been investigated by high-pressure liquid chromatography. Plasma collected 1 min after intravenous injection of cyclic (oxidized) somatostatin showed a single ultraviolet absorbing peak. The total plasma content of this product was equivalent to 10–20% of the injected dose. Amino acid analysis showed that 80–90% of the material in the peak was [des-Ala1]-somatostatin and the remainder was unchanged peptide. [des-Ala1]-Somatostatin is rapidly formed in blood and plasma in vitro and according to other workers may be fully active. In contrast, 1 min after injection of linear (reduced) somatostatin, no products could be detected in the circulation. Incubations in vitro resulted in rapid conversion of the linear somatostatin to a product similar to the cyclic form. However, in vivo, very efficient clearance of linear somatostatin must occur even more rapidly than cyclization. In view of the very different clearance rates of the two forms of somatostatin, it is important to know whether endogenous somatostatin is released in the cyclic or the linear form. The absence of detectable concentrations of inactive peptide fragments in the circulation suggests that inactivation of somatostatin occurs in the tissues.
HISTOENZYMOLOGICAL STUDIES OF 3β- AND 17β-HYDROXYSTEROID DEHYDROGENASES IN THE PLACENTAE AND ADRENAL GLANDS OF BILATERALLY OVARIECTOMIZED RATS
Authors: EMMERICH ANNE , LEGRAND CHANTAL
Published: December 2008

The distribution and activities of 5-unsaturated-3β- and 17β-hydroxysteroid dehydrogenases (HSD) have been studied during the pregnancy of normal and ovariectomized rats on days 17, 19 and 21 post coitum. No hormonal substitution was provided after bilateral ovariectomy on day 15 post-coitum. 5-Unsaturated-3β-HSD was characterized with pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone as substrates; oestradiol-17β and testosterone were used for the investigation of 17β-HSD activity. With these substrates, it was found that the placental and adrenal activities and distribution of 5-unsaturated-3β-and 17β-HSD did not differ in ovariectomized and control rats and it is suggested that increased placental or adrenal steroidogenesis does not supplement deficient ovarian function in order to maintain pregnancy. In the pregnant rat, the ovaries do not control the activities of 5-unsaturated-3β- and 17β-HSD in the placenta.
INVESTIGATIONS INTO THE ROLE OF CALCIUM IONS IN THE CONTROL OF STEROID PRODUCTION BY ISOLATED ADRENAL ZONA GLOMERULOSA CELLS OF THE RAT
Authors: MACKIE CAROLINE , WARREN R. L. , SIMPSON E. R.
Published: December 2008

An increase in the concentration of extracellular potassium from 3·6 to 8·4 mmol/l had only a small delayed effect on the uptake of radioactive calcium by isolated adrenal glomerulosa cells. However, the same stimulus had a rapid and highly significant effect on the efflux of radioactive calcium from glomerulosa cells preloaded with 45Ca2+. Cells incubated in medium containing 8·4 mmol potassium/l had retained approximately 15% more radioactivity than control cells after 2·5 min and this difference was maintained for up to 90 min. There was an increase in the production of steroids by the glomerulosa cells in the presence of 8·4 mm-potassium. No effect on calcium efflux was observed in similar experiments with isolated fasciculata cells; it has been established that this concentration of potassium does not affect steroidogenesis in fasciculata cells, indicating that the effect on glomerulosa cells may be causally linked to steroidogenesis. There was no significant change in the total calcium content of glomerulosa cells in the presence of 8·4 mm-potassium. Exchangeable calcium in these cells was found to be 60% of the total calcium content.
URINARY CALCIUM EXCRETION IN HYPERPROLACTINAEMIA
Authors: HIPKIN L. J. , DAVIS J. C. , DIVER M. J.
Published: December 2008

Sub-department ofEndocrine Pathology, Alder Hey Hospital, Eaton Road, Liverpool, LI2 2AP

(Received 12 September 1977)

Injections of ovine prolactin into normal subjects and certain patients increases the urinary excretion of calcium (McCalister & Welbourn, 1962; Beck, Gonda, Hamid, Morgen, Rubinstein & McGarry, 1964) and hypercalcaemia as well as hypercalcinuria is produced after administration of prolactin to experimental animals (Mahajan, Robinson & Horrobin, 1974). The levels of calcium in the serum and urine of patients with hyperprolactinaemia have therefore been studied.

Fourteen patients (one man, 13 women) were selected on the basis of raised levels of prolactin in the plasma. Clinical details are shown in Table 1. None of the patients had primary hypothyroidism and none was taking drugs except the man (S.B.), who was on cortisone and thyroxine replacement therapy. During the study, patients had their normal diet either at home or in hospital. Plasma prolactin was estimated by radioimmunoassay
STEROIDOGENESIS BY CULTURED GRANULOSA CELLS ASPIRATED FROM HUMAN FOLLICLES USING PREGNENOLONE AND ANDROGENS AS PRECURSORS
Authors: FOWLER R. E. , FOX N. L. , EDWARDS R. G. , WALTERS D. E. , STEPTOE P. C.
Published: December 2008

Human granulosa cells from Graafian follicles aspirated 3–4 h before the expected time of ovulation were incubated with various steroid substrates, including pregnenolone, androstenedione, testosterone and dehydroepiandrosterone (DHA). Steroid production after 3 and 10 h of incubation was determined by radioimmunoassay.

Progesterone and 17α-hydroxyprogesterone were the major products of granulosa cells in control short-term cultures with endogenous substrates. The addition of pregnenolone increased the synthesis of progesterone and 17α-hydroxyprogesterone compared with the controls, although the response varied considerably between paired short-term cultures. Little or no oestradiol-17β was produced from endogenous precursors or short-term cultures to which pregnenolone had been added; one follicle, however, produced similar amounts of oestradiol-17β in the control cultures and after incubation with pregnenolone.

When granulosa cells were cultured with various amounts of androstenedione, DHA or testosterone, large amounts of oestradiol-17β were produced, especially in short-term cultures in which larger amounts of substrate were added. Progesterone production continued and progesterone was synthesized more rapidly or in greater amounts in some short-term test cultures than in the controls.

The results indicate that human granulosa cells are one source of oestradiol-17β during the preovulatory phase. The data support the two-cell theory for oestradiol synthesis, for granulosa cells do not appear to undertake steroid conversion via the 5-unsaturated pathway, but aromatize androgens known to be produced by thecal cells. It is also suggested that either androgens or oestradiol-17β stimulate progesterone production by granulosa cells, at least in vitro.
PARTIAL SYNCHRONY OF THE OESTROUS CYCLES OF RATS INTRODUCED TO A NEW ENVIRONMENT
Authors: SHIRLEY BARBARA
Published: December 2008

Partial synchronization of oestrous cycles was observed in Sprague–Dawley rats with both 4 and 5 day cycles. In groups of rats exhibiting a synchrony of cycles, the number of animals that came into oestrus 4 or 5 days (approximately one cycle) after they were placed in a new environment was significantly greater than the number expected to be in oestrus if cycling was random. An environmental influence was considered to be responsible for the synchrony of the oestrous cycles but a specific stimulus for their synchronization was not identified. Initiation of vaginal smearing was considered to be a factor contributing to cycle synchrony. The introduction of rats to light–darkness cycles and their removal from the presence of other female rats were stimuli tested for their effectiveness in initiating new cycles, and causing the cycles to be synchronized as a consequence, but, when tested, neither of these environmental changes was found to initiate the observed synchrony of cycles.
MEMBRANES FROM A TRANSPLANTABLE OSTEOGENIC SARCOMA RESPONSIVE TO PARATHYROID HORMONE AND PROSTAGLANDINS: REGULATION OF ADENYLATE CYCLASE AND OF HORMONE METABOLISM
Authors: CRAWFORD A. , HUNT N. H. , DAWBORN J. K. , MICHELANGELI V. P. , MARTIN T. J.
Published: December 2008

Adenylate cyclase activity in particulate fractions from a transplantable rat osteogenic sarcoma was stimulated in a dose-dependent manner by prostaglandins E1 and E2 (PGE1 and PGE2) and parathyroid hormone (PTH). Prostaglandin F2α was active at a high concentration (3 × 10− 4 mol/l). Pretreatment of membranes with collagenase plus hyaluronidase reduced the magnitude of the PTH effect but did not affect the size of the PGE1 effect.

Guanosine 5′-triphosphate and its synthetic analogue 5′-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase in particulate preparations from the osteogenic sarcoma. The latter agent produced much larger effects, although the concentrations required for half-maximal enzyme activation were the same for both agonists (approximately 2 × 10−6 mol/l). The effects of PTH and Gpp(NH)p were supra-additive at some concentrations of hormone. The effects of PGE1 and Gpp(NH)p were supra-additive at all hormone concentrations tested. Pre-incubation of membrane particles for 6 min with PTH produced an enzyme activation which was not reversed by dilution through washing; pre-incubation with PGE1 did not produce this effect. The response of membrane adenylate cyclase to Gpp(NH)p (10−4 mol/l) was 75% greater in preparations pre-incubated with PTH than in membranes pre-incubated in buffer alone or in buffer containing PGE1. The basal rate of cyclic AMP production in the adenylate cyclase assay system decreased over a 35 min incubation period. This decrease was prevented by addition of PTH or PGE1. Addition of NaF or Gpp(NH)p produced a steady increase in the rate of production of cyclic AMP with time.

Membrane preparations did not reduce the biological activity of PTH and did not degrade 125I-labelled PTH.

The results demonstrate that the PTH- and PGE-responsive adenylate cyclases of the osteogenic sarcoma have distinctly different properties and that particulate preparations of the tumour do not metabolize PTH.
A METHOD TO STUDY TEMPORAL CHANGES IN ADRENAL ACTIVITY IN RELATION TO SEXUAL STATUS IN THE FEMALE LABORATORY RAT
Authors: PHILLIPS J. G. , POOLSANGUAN W.
Published: December 2008

There is a temporal relationship between the secretory activity of the rat adrenal gland and the stage of the oestrous cycle. In previous studies, adrenal venous blood has been sampled, but because of the stress of a lengthy operation, the gland is subjected to maximum stimulation. A new surgical approach has been developed in which samples of adrenal venous blood are taken within 3 min of contact. A competitive binding radioassay was used to determine the level of corticosterone in samples of plasma of both adrenal venous and peripheral arterial origin obtained before (3 min) and after (15 min) the onset of (presumably) ACTH-induced secretion. A reassessment of adrenal function indicated that adrenal activity peaked in pro-oestrus with higher values in the afternoon than the morning and both values were significantly higher than at any other stage in the oestrous cycle. The variations in the concentration of corticosterone in adrenal venous plasma were reflected by a similar pattern of variation in the level of corticosterone in peripheral arterial plasma. In samples of adrenal venous plasma obtained at 15 min, the level of corticosterone was approximately 25 times higher than the basal value during pro-oestrus and approximately 140 times higher than the values during the other stages of the cycle; for peripheral arterial blood the values were eight and 22–30 times higher respectively, without any significant difference when samples of either type of blood were obtained under stress. This indicates maximum stimulation by endogenous ACTH.

Results obtained after treatment of ovariectomized rats with progesterone and/or oestradiol and the fact that LH, but not ACTH, plays a stimulatory role in the non-stressed metoestrous animal, suggest that the peak of adrenal activity at the time of pro-oestrus might be biphasic: in the morning it is influenced by a high level of oestrogen and a low level of progesterone; in the afternoon this balance is reversed. The effect is secondary to the surge of LH which may have a direct effect on the peak of adrenal activity at this critical period.
STEROID PRIMING OF THE LUTEINIZING HORMONE RESPONSE TO LUTEINIZING HORMONE RELEASING HORMONE
Authors: BECK L. V. , BAY M. , SMITH A. F. , KING D. , LONG R.
Published: December 2008

Perifusion experiments were performed to study the stimulatory effects of luteinizing hormone releasing hormone (LH-RH) on the release of LH from anterior pituitary tissue. Exposure of pituitary tissue from normal male rats to LH-RH (5 ng/ml for 5 min) induced a small release of LH; in tissue from ovariectomized rats receiving no pretreatment, the release was more than three times greater and in tissue from gonadectomized male or female rats pretreated with oestradiol benzoate and progesterone, the release was six times greater than that observed in normal rats. Further exposure of pituitary tissue from gonadectomized steroid-pretreated male and female rats to LH-RH (5 ng/ml) induced an increase in the level of LH even greater than that seen after the initial exposure (priming action of LH-RH); in tissue from ovariectomized rats receiving no pretreatment, less LH was released than after the first exposure to LH-RH and in tissue from normal male rats the response was unchanged.
PLASMA OESTRADIOL AND DELAYED OVULATION AFTER ADMINISTRATION OF SODIUM PENTOBARBITONE TO PRO-OESTROUS 5 DAY CYCLIC RATS
Authors: VAN DER SCHOOT P.
Published: December 2008

Injection of sodium pentobarbitone (Nembutal) into rats between 12.00 and 13.00 h on the day of pro-oestrus was fully effective in blocking the expected ovulation. In 75% of the rats, ovulation of the present generation of large follicles occurred 24 h later (delayed ovulation). Injection of Nembutal between 12.00 and 13.00 h on the day of pro-oestrus and at the same time on the subsequent day was fully effective in blocking the ovulation twice: in only two rats out of 13 did ovulation of the present generation of follicles still occur. When unilateral ovariectomy was performed immediately after injection of a single dose of Nembutal into pro-oestrous rats, delayed ovulation was significantly inhibited. However, after inhibition of ovulation by either two injections of Nembutal or one injection and unilateral ovariectomy, delayed ovulation could be induced by treatment with a small dose of oestradiol benzoate during the Nembutal-induced anaesthesia. It thus seemed that delayed ovulation failed because of disruption of oestrogen production after administration of Nembutal. The concentration of oestradiol-17β in the plasma of Nembutal-treated pro-oestrous rats decreased rapidly during the 24 h after treatment. It is concluded that this decrease in the concentration of oestradiol is due to the inherent ageing of preovulatory follicles manifesting itself when exposure to the ovulatory surge of LH is inhibited.
LABELLING OF THE THYROID CELL SURFACE WITH 125I
Authors: POVEY PAMELA M. , REES SMITH B. , HALL R.
Published: December 2008

The surface membrane proteins of cultured porcine thyroid cells have been labelled with 125I by the lactoperoxidase method. Evidence that the labelling was restricted to the cell surface was supported by the high viability of the cells in suspension, the high proportion of labelled material in the particulate fraction after homogenization and electronmicroscopic autoradiographic studies. The labelled proteins were analysed by electrophoresis on polyacrylamide gels containing sodium dodecyl sulphate and this indicated the presence of ten major labelled protein bands with approximate molecular weights of 175 000, 155 000, 135 000, 88 000, 80 000, 52 300, 39 000, 30 000, 21 000 and 14 300. Comparison of the electrophoretic patterns obtained with cultured human and porcine thyroid cells suggested that there were species differences in the proportions of lower-molecular-weight proteins.
PURIFICATION AND SOME PROPERTIES OF OVINE PLACENTAL LACTOGEN
Authors: REDDY S. , WATKINS W. B.
Published: December 2008

A method has been described for the purification of ovine placental lactogen (oPL) involving the use of freshly obtained sheep foetal cotyledons. Tissue was extracted with 0·1 m-ammonium bicarbonate and the supernatant fraction, adjusted to pH 7, was brought to 60% saturation with ammonium sulphate. The resulting precipitate was then subjected to a sequence of chromatographic steps using columns of Sephadex G-100 and carboxymethylcellulose. During each stage of the purification, the lactogenic activity was monitored with a pregnant rabbit mammary gland radioreceptor assay. The yield of oPL corresponded to 8 mg/kg wet foetal tissue and the oPL possessed lactogenic activity equivalent to 1 mg ovine prolactin/mg protein and GH-like activity equivalent to 0·8 mg human GH/mg protein. The biological activity of oPL was confirmed using a rabbit intraductal mammary gland assay in vivo.

After polyacrylamide gel electrophoresis at pH 8·9, oPL was resolved into one major band (isoelectric point 8·2–8·4) and four minor components, which were thought to be deamidation products of oPL. Microimmunoelectrophoresis and immunodiffusion studies confirmed that the preparation of oPL was free from serum protein contaminants.
RAT MYOMETRIAL ACTIVITY IN VIVO: EFFECTS OF OESTRADIOL-17β AND PROGESTERONE IN RELATION TO THE CONCENTRATIONS OF CYTOPLASMIC PROGESTERONE RECEPTORS
Authors: DOWNING SANDRA J. , LYE S. J. , BRADSHAW JANE M. C. , PORTER D. G.
Published: December 2008

The amplitude, frequency and rate of rise of intra-uterine pressure cycles in rats (postpartum, ovariectomized) were unaffected by treatment with progesterone. Amplitude was also unaffected by a combination of treatments with progesterone and oestradiol-17β, which was adequate to ensure the survival of 84% of foetuses in ovariectomized pregnant rats. The failure of progesterone to influence myometrial activity could not be attributed to a lack of 'true' progesterone receptors since these were present in the myometria of the test animals in concentrations exceeding those of oestrous animals. Evidence was obtained which suggested that a high-affinity binding protein, different from the 'true' receptor may predominate in the myometrium of the pregnant rat. Oestradiol-17β in single or repeated doses of from 0·25 to 5 μg, however, was found to reduce the frequency of pressure cycles but to increase significantly their rate of rise of pressure. There was a latency of 6–8 h in these effects of oestradiol. The possibility that inhibition of the myometrium by oestrogen may play a part in the preparation for parturition is discussed.
PROLONGED OESTROGENIC AND MITOGENIC ACTIVITY OF TAMOXIFEN IN THE OVARIECTOMIZED MOUSE
Authors: MARTIN L. , MIDDLETON E.
Published: December 2008

A dose of tamoxifen (ICI 46,474), which has been found to inhibit the vaginal smear response to oestrogens, exerted prolonged oestrogenic effects in mice and increased the rate of cell proliferation in both the vagina and uterus. The vaginal epithelium became multilayered with stratified or cornified surface layers and the uterus developed gross cystic glandular hyperplasia. This demonstrates that ICI 46,474 is simply a weak oestrogen in the mouse.
CIRCADIAN VARIATIONS IN CORTISOL CONCENTRATIONS IN THE PLASMA OF FEMALE RHESUS MONKEYS
Authors: LESHNER A. I. , TOIVOLA P. T. K. , TERASAWA E.
Published: December 2008

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

(Received 25 January 1978)

Diurnal variations in the adrenal secretion of glucocorticoids have been described in a wide range of species. Among primates, most attention has been devoted to man (e.g. Krieger, 1970; Rose, Kreuz, Holaday, Sulak & Johnson, 1972), although the secretion of cortisol in the male rhesus monkey has also been examined (e.g. Michael, Setchell & Plant, 1974; Holaday, Meyerhoff & Natelson, 1977). We present here a report of circadian variations in the concentration of cortisol in the plasma throughout the menstrual cycle of the female rhesus monkey.

Three intact female rhesus monkeys (Macaca mulatta) were adapted to chronic restraint in primate chairs for several months. After confirmation of normal menstrual cycles, a chronic indwelling catheter (Silastic Medical Grade Tubing, 20-gauge, Dow Corning) was inserted. The catheter was placed into the right atrium via the internal
EFFECTS OF AGE AND OVARIAN FUNCTION ON THE PITUITARY–THYROID SYSTEM IN FEMALE RATS
Authors: CHEN H. J. , WALFISH P. G.
Published: December 2008

The effects of ovariectomy and ovariectomy and treatment with oestradiol benzoate (OB) on the basal concentration of thyrotrophin (TSH), the total concentrations and concentrations of free tri-iodothyronine (T3) and thyroxine (T4), and the concentrations of TSH, T3 and T4 observed after treatment with thyrotrophin releasing hormone (TRH) were studied in old (16–17 months of age) constant oestrous and young (3–4 months of age) oestrous rats. The untreated old control rats had significantly (P< 0·001) lower basal total T4 concentrations and percentage and absolute concentrations of free T4 and lower percentage and absolute concentrations of free T3 than untreated young rats. The basal levels of TSH in these two groups were similar and the increases in TSH after injection of TRH were identical. Two weeks after ovariectomy, no significant additional differences in hormone concentrations between old and young rats were observed. However, release of TSH induced by TRH was increased by three- to fourfold in old rats after ovariectomy compared with nine- to tenfold in young ovariectomized rats (P<0·01). Basal T4 concentrations remained unchanged in old ovariectomized rats treated for 7 days with 2 μg OB/day compared with both intact and ovariectomized rats. However, T4 concentrations in OB-treated young rats were significantly (P<0·001) reduced. Treatment with OB significantly increased both basal and TRH-induced T3 and TSH levels in old and young rats although the young rats showed a greater response (P<0·001). Two hours after injection of TRH, serum T3 concentrations in old rats increased only after OB treatment and not after ovariectomy alone or in intact rats, whereas T3 concentrations rose in all three groups of young animals.

These results indicate that (1) older female rats have lower total T4, free T4 and free T3 concentrations and a lower TSH response to TRH, (2) OB treatment in young rats suppresses serum T4 but increases serum T3 and results in a greater TSH response to TRH and (3) at least one of the mechanisms accounting for the alterations in thyroid function observed in the older female rat, in addition to possible concomitant primary thyroid gland hypofunction, is a hyporesponsiveness of pituitary thyrotrophs to both endogenous negative feedback signals from low serum thyroid hormone concentrations and exogenous TRH stimulation.
SPECIFIC CHANGE IN THE DIRECTION OF PROSTAGLANDIN SYNTHESIS BY INTRA-UTERINE TISSUES OF THE RHESUS MONKEY (MACACA MULATTA) DURING LATE PREGNANCY
Authors: MITCHELL M. D. , CLOVER L. , THORBURN G. D. , ROBINSON J. S.
Published: December 2008

The rates of production of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-oxo-prostaglandin F (PGFM) by intra-uterine tissues from pregnant monkeys in vitro have been determined using a method of tissue superfusion. The amnion, chorion, placenta, decidua basalis, decidua parietalis and myometrium were obtained at Caesarean section during late pregnancy. Production of PGE by all tissues was significantly lower at term than during late pregnancy, whereas production of PGF by the amnion, chorion, decidua parietalis and myometrium was significantly greater. All tissues produced significantly more PGE than PGF and also, excepting the decidua basalis and decidua parietalis, more PGFM than PGF. Close to parturition the amnion was quantitatively (per unit weight) the major source of prostaglandins. It is suggested that a specific change in the direction of prostaglandin synthesis by intra-uterine tissues occurs near parturition in the rhesus monkey.
RECURRENT BREEDING SEASONS IN PINEALECTOMIZED OR OPTIC-NERVE-SECTIONED FERRETS
Authors: HERBERT J. , STACEY PAMELA M. , THORPE D. H.
Published: December 2008

The breeding seasons of two groups of pinealectomized ferrets and one group of blind ferrets, with appropriate controls, were observed for up to 5 years after the operations. All animals showed recurrent breeding seasons. Both pinealectomized and blind animals became increasingly asynchronous after the first season, but showed no evidence of a free-running, endogenous circannual periodicity nor of synchronization to light or other environmental cues.
UPTAKE AND BINDING OF GLUCOCORTICOIDS IN FISH TISSUES
Authors: PORTHÉ-NIBELLE JACQUELINE , LAHLOU BRAHIM
Published: December 2008

Cytosols prepared from the liver and various tissues of goldfish (intact or hypophysectomized) and trout (intact) were incubated at 2 °C in the presence of tritiated cortisol or dexamethasone (3 × 10−9 to 3 × 10−6 mol/l) with or without a 1000-fold excess of unlabelled steroid. In contrast to mammals, the specifically bound component represented a very low fraction of the total bound steroid retained on DEAE cellulose filters and did not show saturation over a large range of concentrations.

The subcellular distribution of [3H]dexamethasone was studied in trout liver after intravascular injection of the labelled steroid with and without an excess of unlabelled steroid.

The amount of protein-bound steroid in the cytosol again corresponded to a small (4%) proportion of the free steroid. The large reduction in the uptake of tritiated dexamethasone, which was induced in both the cytosol and nuclei by competing unlabelled dexamethasone, was interpreted as evidence for mediated entry across cellular and nuclear membranes.

These results indicate that high-affinity binding sites are absent, or present only in very small numbers in cytosol from teleost tissues. The entry of glucocorticoids into the nucleus may not require the hormone to be bound to high-affinity cytosolic receptors unless the binding, though quantitatively small, displays a high rate of turnover.
FAILURE OF SODIUM LOADING TO INFLUENCE THE CONCENTRATION OF ISO-RENIN IN RAT BRAIN
Authors: HUSAIN A. , JONES C. W. , DAY M. D.
Published: December 2008

Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Clifton Boulevard, Nottingham, NG7 2UH

(Received 23 February 1978)

In addition to its well-known peripheral actions, angiotensin II has been implicated in central nervous mechanisms concerned with the modulation of blood pressure, drinking, the release of antidiuretic hormone (ADH) and the secretion of adrenocorticotrophin (ACTH; see Severs & Daniels-Severs, 1973). The receptors responsible for mediating these central effects are both central and peripheral in relation to the blood–brain barrier. Because angiotensin II does not cross this barrier rapidly (Volicier & Loew, 1971), the physiological significance of the receptive sites for angiotensin II which lie on the central side of the barrier (e.g. in the mid-brain peri-aqueductal grey matter and the supraoptic nucleus of the hypothalamus) is unclear.

Recently, an independent iso-renin-angiotensin system has been demonstrated in the central nervous system (for review see Ganten, Hutchinson, Schelling, Ganten & Fisher, 1976)
MATURATIONAL CHANGES IN THE CHARACTERISTICS OF OESTROGEN-INDUCED SURGES OF LUTEINIZING HORMONE IN IMMATURE DOMESTIC GILTS
Authors: ELSAESSER F. , FOXCROFT G. R.
Published: December 2008

Institute für Tierzucht und Tierverhalten, FAL, Mariensee, 3057 Neustadt 1, Federal Republic of Germany and * PES-Animal Physiology, University of Nottingham, School of Agriculture, Sutton Bonington, Loughborough, LE12 5RD

(Received 19 April 1978)

Possible causes of the variability in oestrogen-induced surges of luteinizing hormone (LH) in prepubertal miniature (Elsaesser, Parvizi & Ellendorff, 1978) and domestic (Foxcroft, 1978) gilts have been investigated.

Four groups of six German Landrace gilts with indwelling jugular cannulae were kept under conditions of natural daylight. Groups A and C (60 and 161 days old respectively) received 60 μg oestradiol benzoate (OB)/kg body weight (Progynon Oleosum, Schering); groups and D (60 and 161 days) received 600 μg/kg body weight. Concentrations of OB (Elsaesser et al. 1978) and LH (Foxcroft, Pomerantz & Nalbandov, 1975) were determined in plasma samples taken at least every 12 and 4h, respectively, for 79·5 h after the i.m. injection of oil and for
INHIBITION OF GONADOTROPHIN SECRETION BY INDUCED HYPERPROLACTINAEMIA IN THE MALE RAT
Authors: McNEILLY A. S. , SHARPE R. M. , DAVIDSON D. W. , FRASER H. M.
Published: December 2008

Pituitary glands were transplanted under the kidney capsule to induce hyperprolactinaemia in both immature (41 days old) and adult (150 days old) intact male rats. Blood samples were taken for hormone analysis at regular intervals after transplantation and the animals were killed 42–45 days after the operation.

Serum levels of prolactin rose in all groups of rats with transplants except in those animals bearing only one pituitary gland. Increased adrenal weight in all transplanted groups suggested that effective hyperprolactinaemia was always achieved. Serum levels of LH and FSH were significantly suppressed in all animals with transplants; the pituitary LH content was as reduced in all animals except those bearing one pituitary transplant but reductions in the pituitary FSH content were inconsistent. Although the amount of luteinizing hormone releasing hormone (LH-RH) in the hypothalamus did not differ significantly between groups, the effects of hyperprolactinaemia on serum and pituitary levels of LH and FSH suggested a functional lack of LH-RH (possibly due to an increase in the sensitivity of the hypothalamus to the negative feedback effects of testicular steroids).

Serum levels of testosterone remained normal in spite of reductions in the serum concentrations of LH and FSH and, in immature animals, a reduction in testicular binding of LH/human chorionic gonadotrophin.

These results are discussed in the light of previous conflicting reports on the effects of induced hyperprolactinaemia on the regulation of secretion of LH and FSH.
FUNCTIONAL SIGNIFICANCE OF THE CELLS IN THE PARS ANTERIOR OF THE PITUITARY GLAND OF THE MUSK SHREW (SUNCUS MURINUS L.)
Authors: NAIK D. R. , DOMINIC C. J.
Published: December 2008

Seven morphologically and tinctorially distinct types of cell (types 1–) have been distinguished in the pars anterior of the pituitary gland of the musk shrew (Suncus murinus L.). On the basis of their responses to various experimental stimuli, these cell types were correlated with the secretion of various trophic hormones. Type 1 cells exhibited conspicuous changes after thyroidectomy or inactivation of the thyroid gland and hence appeared to be the source of TSH. Types 2 and 3 cells responded to gonadectomy and administration of androgens, which suggests that they were associated with gonadotrophin secretion. The granules of the type 2, but not the type 3 cells could be extracted with 10% trichloroacetic acid, which may indicate that type 2 and 3 cells secrete FSH and LH respectively. After the administration of either reserpine or oestrogen, the type 4 cells underwent hypertrophy and hyperplasia, which suggests that they were the likely source of prolactin. Type 6 cells, which are distinguishable from type 4 cells by their thinly dispersed erythrosinophilic granulation, showed conspicuous changes after unilateral adrenalectomy, administration of metyrapone or exposure to stress and may therefore be responsible for secretion of ACTH. Type 5 cells tinctorially resembled the somatotrophic cells of other mammalian species and did not respond to any of the experimental treatments used in the present study. It is therefore possible that these cells have a somatotrophic function. The possible significance of type 7 cells has been discussed previously.
SEXUAL DIFFERENCE IN THE EFFECT OF CYPROTERONE ACETATE AND GLUCOCORTICOIDS ON α2u-GLOBULIN IN GONADECTOMIZED RATS
Authors: VANDOREN G. , HEYNS W. , VERHOEVEN G. , DE MOOR P.
Published: December 2008

Laboratorium voor Experiméntele Geneeskunde, Katholieke Universiteit Leuven, Rega Instituut, Minderbroedersstraat 10, B-3000 Leuven, Belgium

(Received 28 March 1978)

The synthesis of α2u-globulin, the major protein found in the urine of adult male rats (Roy & Neuhaus, 1966; Roy, Neuhaus & Harmison, 1966), is controlled by several hormones. Androgens, growth hormone, thyroxine and glucocorticoids promote the synthesis of this protein, whereas oestrogens and a factor secreted by ectopically transplanted pituitary glands suppress it (Roy & Neuhaus, 1967; Roy, 1973; Kurtz, Sippel & Feigelson, 1976; Vandoren, Van Baelen, Verhoeven & De Moor, 1978). Cyproterone acetate (CA), a potent antiandrogen, inhibits the androgenic induction of α2u-globulin in ovariectomized rats, but does not suppress its synthesis in intact male rats (Roy, 1976). In the present experiments, the influence of CA on the induction of α2u-globulin by testosterone propionate (TP) in the serum of gonadectomized male and female rats was compared. Evidence is presented for
EFFECT OF RESERPINE ON PLASMA CONCENTRATIONS OF GROWTH HORMONE AND PROLACTIN IN THE DOMESTIC FOWL
Authors: HARVEY S. , SCANES C. G. , CHADWICK A. , BOLTON N. J.
Published: December 2008

Department of Zoology, University of Hull, Hull, HU6 7RX, * Department of Physiology, Rutgers University, New Brunswick, New Jersey 08903, U.S.A. and †Department of Pure and Applied Zoology, University of Leeds, Leeds, LS2 9JT

(Received 9 June 1978)

It has been established that biogenic amines are involved in control of the secretion of prolactin (MacLeod, 1976) and growth hormone (GH; Martin, 1976) in mammals. In birds there is very little evidence for this, although in the domestic fowl it has recently been demonstrated that sytemically administered catecholamines (adrenaline and noradrenaline) markedly lower the concentration of GH in the peripheral plasma (Harvey & Scanes, 1978) and that serotonin stimulates the release of prolactin from incubated hemipituitary glands (Border & Chadwick, 1977). Therefore, to elucidate further the possible involvement of biogenic amines in the regulation of GH and prolactin secretion, the effect of reserpine (a 5-hydroxytryptamine- and catecholamine-depleting agent) on the concentrations
STEROIDAL CONTROL OF THE RELEASE OF THE PREOVULATORY SURGE OF LUTEINIZING HORMONE IN THE RAT
Authors: WILSON CATHERINE A. , HADLEY J. C. , GILBERT D. , McNEILLY A. S.
Published: December 2008

Experiments were carried out on 4 day cyclic rats or immature rats induced to ovulate by administration of pregnant mare serum gonadotrophin. Removal of the ovaries and adrenal glands at 17.00 h of pro-oestrus, i.e. after the critical period, prevented the appearance of the surge of LH. Sham-operation or removal of only one of the sets of glands had no effect. This indicates that the preovulatory increase in the concentration of oestradiol is not solely responsible for the surge of LH; the presence of a steroid, secreted by the ovaries and adrenal glands in the late afternoon of pro-oestrus, is also required.

Attempts were made to reinstate the surge of LH in ovariectomized, adrenalectomized rats by administration of one of the steroids normally secreted in late pro-oestrus. Corticosterone, 20α- and 20β-hydroxy-4-pregnen-3-one and 17α-hydroxyprogesterone all had no effect. Progesterone injected at the time of the operation stimulated the release of LH but only after the plasma concentration had reached its maximum 3–5 h after injection. Testosterone also stimulated the release of LH some hours after administration.
POSSIBLE NEONATAL IMPRINTING OF LUTEINIZING HORMONE FEEDBACK BY TESTOSTERONE IN MALE RATS
Authors: BERAUD G. , AUDRAIN M.
Published: December 2008

Université de Rennes, Laboratoire de Physiologie des Régulations, UER des Sciences Biologiques, 35031 Rennes Cedex, France

(Received 3 May 1978)

The results described by Naftolin, Ryan, Davies, Reddy, Flores, Petro, White, Takaoka & Wolin (1975) and Moguilevsky, Scacchi & Rubinstein (1977) indicate that the aromatization of androgens to oestrogens during the neonatal period provides a probable route of action for the testicular androgens. It is also thought that during this critical period, the conversion of androgens to oestrogens is involved in regulation of the hepatic and adrenal enzymes that metabolize steroid hormones (De Moor, Verhoeven & Heyns, 1973; Goldman, Gustafsson & Stenberg, 1974; Gustafsson & Stenberg, 1974). There is considerable evidence that androgens inhibit the secretion of luteinizing hormone (LH) when administered to immature and mature male rats immediately after castration (Mahesh, Muldoon, Eldridge & Korach, 1975; Moger, 1976; Shin & Howitt, 1976). The purpose of the present investigation was
DIRECT ANTIPROLIFERATIVE EFFECT OF DOPAMINE AGONISTS ON THE ANTERIOR PITUITARY GLAND IN ORGAN CULTURE
Authors: PAWLIKOWSKI M. , KUNERT-RADEK J. , STĘPIEŃ H.
Published: December 2008

Department of Experimental Endocrinology, Institute of Endocrinology, Medical Academy of Łódź, Dr Sterling sir. 3, 91–425 Łódź, Poland

(Received 22 May 1978)

Lloyd, Meares & Jacobi (1975) observed inhibition of mitotic activity in the anterior pituitary gland by the dopamine receptor agonist, bromocriptine, in oestrogen-treated male rats. This observation has been confirmed in our laboratory (Stępień, Wolaniuk & Pawlikowski, 1978). Suppression of mitotic activity in the pars intermedia of the rat pituitary gland by bromocriptine has also been observed (Rychter & Stępień, 1977). Furthermore, it has been found that the dopamine receptor blocker, pimozide, enhances mitotic activity in the rat anterior pituitary gland (Stępień et al. 1978). By the use of various ergot alkaloids, MacLeod & Lehmeyer (1973) succeeded in inhibiting the growth of transplantable rat pituitary tumours. There have also been observations suggesting an antiproliferative effect of bromocriptine on human pituitary tumours (Wass, Thorner, Morris, Rees, Mason, Jones &
EFFECT OF LUTEINIZING HORMONE ON THE CONCENTRATION OF CYCLIC GMP IN RABBIT OVARIES
Authors: PATWARDHAN V. V. , LANTHIER A.
Published: December 2008

Laboratoire d'Endocrinologie, Hôpital Notre-Dame et Département de Medicine, Université de Montréal, Montréal, Canada

(Received 28 June 1978)

Cyclic AMP has been implicated as an intermediate in some of the actions of luteinizing hormone (LH) on ovarian tissues, such as stimulation of steroidogenesis (LeMaire & Marsh, 1975). Both in vitro (Marsh, Butcher, Savard & Sutherland, 1966) and in vivo (Armstrong, Dorrington & Robinson, 1976), stimulation with LH results in a rapid increase in the amount of cyclic AMP in ovarian tissues, which precedes the LH-induced increase in steroidogenesis. Recently, studies on rat ovaries (Grinwich, Ham, Hichens & Behrman, 1976; Ratner, 1976; Ratner & Sanborn, 1976) have indicated that the ovarian tissue content of cyclic GMP may also be regulated by LH, but in a direction opposite to that of cyclic AMP. In the rabbit, Goff & Major (1975) have shown that administration of human chorionic gonadotrophin (HCG) causes a biphasic increase
DEPENDENCE OF GLUTAMINE METABOLISM AND AMMONIA SYNTHESIS ON SEX IN RAT KIDNEY SLICES
Authors: GEORGE J. P. , SOLOMON S.
Published: December 2008

The uptake and metabolism of glutamine, production of ammonia and consumption of O2 were studied in kidney slices isolated from mature, gonadectomized and newborn male and female rats in the presence of 0·05, 0·5, 2 and 5 mm-glutamine. Slices isolated from mature intact female rats showed significantly greater conversion of glutamine into CO2 and NH3 without any change in the total uptake of glutamine when compared with all other experimental groups. No difference in O2 consumption was found between mature male and female animals. Ovariectomy reduced glutamine metabolism, NH3 production and O2 consumption without any effect on the total uptake of glutamine. In contrast, castration did not significantly affect glutamine metabolism and production of NH3 but did reduce O2 consumption. Newborn (20- to 21-day-old) rats showed no sex-dependent differences in glutamine uptake and metabolism, production of NH3 and consumption of O2, but values for all these parameters were lower in kidney slices from newborn animals than in kidney slices from mature, intact or gonadectomized male and female rats. It is concluded that in female rats, metabolism of glutamine and production of NH3 may be influenced by ovarian sex hormones.
EFFECTS OF ACTIVE IMMUNIZATION OF FEMALE RABBITS AGAINST TESTOSTERONE
Authors: ARMSTRONG R. W. , GAULDIE J. , YOUNGLAI E. V.
Published: December 2008

Prepubertal (immature) and mature female rabbits were actively immunized against testosterone-3-oxime-bovine serum albumin over a period of 11 weeks. The antibody titre was significant in all animals by 5 weeks. The concentration of FSH in prepubertal animals decreased significantly (P< 0·001) between weeks 1 and 5, but no significant changes were observed in the concentration of LH at any time. After immunization for 8 weeks, there was a significant (P< 0·05) increase in the serum concentration of androgen and the percentage of bound testosterone also increased (P< 0·05). The serum concentration of oestradiol increased after immunization for 11 weeks, compared with values at 8 weeks (P<0·05) and oestradiol binding also rose by week 5 (P<0·01). Libido was not affected and significantly (P< 0·005) increased numbers of ovulations were noted in immunized animals. These results suggest that immunization of the female rabbit against testosterone may disrupt the normal regulation of follicular maturation.
EFFECT OF NEONATAL ANDROGEN TREATMENT AND ORCHIDECTOMY ON PITUITARY LEVELS OF GROWTH HORMONE IN THE RAT
Authors: SOMANA REON , VISESSUWAN SERMSRI , SAMRIDTONG AYUDHYA , HOLLAND R. C.
Published: December 2008

Department of Anatomy, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, Thailand

(Received 19 July 1978)

Sex hormones have been shown to influence the levels of growth hormone (GH) in rats and mice (Birge, Peake, Mariz & Daughaday, 1967; Callahan, Somana & Srikhao, 1972; Sinha, Selby, Lewis & VanderLaan, 1972). Since treatment of neonatal female rats with androgens changes the pattern of gonadotrophin secretion from the cyclic female type to the non-cyclic male type (Gorski, 1971; Dorner, 1977), it was thought to be of interest to discover whether this treatment alters the pituitary GH content in female rats to levels similar to those found in male rats before and after puberty and whether after neonatal orchidectomy there is a reduction in the pituitary GH content to levels found in normal female rats.

Newborn rats of a Fisher strain were divided into four groups: normal male, orchidectomized male and normal