bluuebunny/crossref_metadata_2025 huggingface dataset:
SELF-LICKING AND MAMMARY DEVELOPMENT DURING PREGNANCY IN THE RAT
Authors: ROTH L. L. , ROSENBLATT J. S.
Published: December 2008

Stimulation of the nipple lines and genital and pelvic regions by self-licking, found previously to increase during pregnancy in the rat, was studied for its effect on mammary gland development. Licking was prevented by fitting wide rubber collars around the necks of rats for the entire period of pregnancy or for either the first half (days 1–12) or the second half (days 12–22) of pregnancy. The percentage of secretory tissue, and ratings of lobulo-alveolar (L-A) development and secretory (S) activity were used to measure the development of the gland on either the 22nd or the 12th day of pregnancy. Notched collars, which permitted licking, were used as a control for any stress effects that resulted from the collars, and injections of formalin were used as a control for any stress produced by the collar. Mammary development was reduced to only 50% of normal, and L-A development and S-activity ratings showed a corresponding retarded development in animals wearing a collar throughout pregnancy. Notched collars did not affect gland development and formalin injections accelerated it. There was no difference in the effects of wearing a collar during the first or second half of pregnancy: both groups were equal in gland development on the 22nd day and their glands were more developed than those of females wearing a collar throughout pregnancy. In animals that wore collars from the beginning of pregnancy, gland development was already retarded (28%) by mid-pregnancy. Rats whose glands were reduced in development during the first half of pregnancy showed less nipple-line licking during the second half of pregnancy. These findings indicate that stimulation provided by self-licking contributes significantly to mammary gland development during pregnancy and, therefore, the activity of the gland before parturition, like lactation post partum, is regulated in part by external stimulation.
ADRENAL FUNCTION IN BREAST CANCER: PRODUCTION AND METABOLIC CLEARANCE RATE OF CORTISOL IN PATIENTS WITH EARLY OR ADVANCED BREAST CANCER AND IN NORMAL WOMEN *
Authors: JENSEN V. , DESHPANDE N. , BULBROOK R. D. , DOOUSS T. W.
Published: December 2008

The production rate of cortisol in patients with early or advanced breast cancer was compared with that of controls of comparable age. The miscible pool of this hormone was raised in advanced breast-cancer patients due to a higher production rate. The plasma clearance of cortisol remained unaffected, resulting in a higher titre of cortisol (both total and unbound) in advanced breast-cancer patients. There was no significant difference in the production rate between the early breast-cancer cases and controls.

The binding of cortisol to transcortin was studied in all cases. The amount of unbound cortisol was raised in advanced breast-cancer cases. There was a significant correlation between both total and unbound cortisol and the production rate of this hormone. The latter correlation suggests that there is no abnormality in the hepatic extraction of cortisol in these patients.

The metabolic clearance rate was found to be of the order of the blood flow through the liver when unbound cortisol was used for its estimation, showing that it is the unbound cortisol which is removed by the liver.
TREATMENT OF EUNUCHOIDAL MEN WITH HUMAN CHORIONIC GONADOTROPHIN AND FOLLICLE-STIMULATING HORMONE
Authors: CROOKE A. C. , DAVIES A. G. , MORRIS R.
Published: December 2008

Large doses of human chorionic gonadotrophin and human pituitary follicle-stimulating hormone were given singly and in combination to six eunuchoidal men. None had an increased excretion of urinary gonadotrophin before treatment.

Histological examination of the testicles showed very immature germinal epithelium in five of the patients before treatment. Spermatozoa were found histologically in three patients, only after combined treatment with both gonadotrophins. Low concentrations of spermatozoa appeared in semen from two of these patients.

One patient was found to have histological evidence of spermatogenesis before treatment but was unable to produce semen. Treatment with chorionic gonadotrophin alone enabled him to produce semen containing up to 15,000,000 spermatozoa per ml.

Significant increases were found in the urinary levels of a variety of steroids and in total body potassium after treatment with chorionic gonadotrophin and a variable amount of somatic development took place.
THE ASSAY OF SECRETIN IN THE RAT
Authors: HEATLEY N. G.
Published: December 2008

Some characteristics of the pancreas of the rat relevant to the assay of secretin are described, including mean basal flow rate and output of bicarbonate, minute-by-minute changes in rate of flow after different doses of secretin, dose—response relationships, and quantitative differences between the sexes. The coefficient of variation for a single determination of secretin was found to be 15·6%.

Highly active secretin had no ecbolic effect, but pure cholecystokininpancreozymin (CCK-PZ) had a strong hydrelatic action. It is therefore formally impossible to assay secretin accurately in the presence of unknown amounts of CCK-PZ. This limitation applied to the cat also. Possible remedies are discussed.

Crude preparations of secretin hydrochloride of very low potency which have been used as standards since 1955 appear to have suffered no loss of activity over several years. The value of the Hammarsten Cat Unit and of the Clinical Unit which is based on it seems to be substantially different in 1967, compared with earlier values, when assayed in the rat.
DETERMINATION OF SOLVOLYSED SULPHATE ESTERS OF DEHYDROEPIANDROSTERONE AND ANDROSTERONE IN HUMAN PERIPHERAL PLASMA BY GAS-LIQUID CHROMATOGRAPHY
Authors: WANG D. Y. , BULBROOK R. D. , THOMAS B. S. , FRIEDMAN M.
Published: December 2008

A gas—liquid chromatographic method is described for the routine determination as the chloromethyldimethylsilyl ethers of plasma dehydroepiandrosterone and androsterone obtained after solvolysis of a steroid sulphate fraction. 5α-Dihydrotestosterone sulphate is used as an internal standard.

The levels of dehydroepiandrosterone sulphate and androsterone sulphate have been measured in 61 males and 66 females aged 20 days to 91 yr. The steroid levels show an abrupt rise at the age of about 7 yr. and reach a peak between the ages of 20 and 30 yr. Thereafter they fall with advancing age.

The mean level of dehydroepiandrosterone sulphate is significantly higher in adult men than in women but the mean level of androsterone sulphate is similar.
A BIOASSAY METHOD IN VITRO FOR PARATHYROID HORMONE
Authors: ZANELLI J. M. , LEA D. J. , NISBET J. A.
Published: December 2008

A parallel-line bioassay for parathyroid hormone in vitro, based on the release of calcium from 6-day-old mouse calvaria maintained in tissue culture has been developed. The method has been compared with the Munson assay, and it offers the advantages of increased sensitivity, a wider dose-range, greater precision, and symmetrical data suitable for easy statistical analysis. The log.-dose response is linear over the range 0·01–1·0 units, and the mean index of precision was 0·15.
THE EFFECT OF UTERINE ANASTOMOSIS ON THE ACTION OF AN INTRA-UTERINE DEVICE IN THE RAT
Authors: MARSTON J. H. , KELLY W. A.
Published: December 2008

In the rat, when luminal continuity was established between the two uterine horns, a unilateral intra-uterine device (IUD) exerted a complete, bilateral contraceptive effect. This was related to the elimination of blastocysts from both uterine horns and to the bilateral inhibition of the decidual cell reaction. Both uterine horns showed leucocytic infiltration into the endometrium, although infiltration was greater in the IUD horn than in the control horn.

When the uterine horns were united without the establishment of luminal continuity a unilateral IUD exerted a strictly unilateral effect, and leucocytic infiltration was only detected in the IUD endometrium and uterine lumen.

These results support the view that the environment within the separate or continuous uterine lumina was altered in the presence of an IUD so that the decidual cell response was inhibited and blastocysts were eliminated. The possibility that this change was related to leucocytic infiltration into the endometrium and uterine lumen cannot be eliminated.
THE ROLE OF THE PITUITARY GLAND IN IMPLANTATION IN THE MOUSE: DELAY OF IMPLANTATION BY HYPOPHYSECTOMY AND NEURODEPRESSIVE DRUGS
Authors: BINDON B. M.
Published: December 2008

The optimum conditions for delay of implantation by hypophysectomy and neurodepressive agents are described. Hypophysectomy on day 1 without hormone replacement was followed by retarded development and subsequent degeneration of zygotes. Viability of blastocysts was maintained under these conditions by a single injection of a long-acting progestagen on day 1. Hypophysectomy at intervals beginning late on day 3 indicated that implantation is initiated by pituitary activity in the several hours around midnight of this day. In animals induced to ovulate and copulate by exogenous gonadotrophin injections, the corresponding time of pituitary activity was delayed by approximately 8 hr. This delay could not be explained solely on the basis of altered times of ovulation. It is evident that the events of early pregnancy do not follow the normal physiological pattern under these conditions, and caution should be exercised in utilizing such animals.

Of five neurodepressive agents examined, only trifluoperazine effectively delayed implantation. The effect of this substance injected at various times on day 3 of pregnancy suggests that implantation in the mouse is initiated by neurally regulated pituitary activity between 16.00 and 24.00 hr. on this day. Comparison with the mechanism of ovulation indicates that ovulation and implantation are regulated by separate hypothalamic-pituitary events, one peculiar to the oestrous cycle, the other to early pregnancy.
THE EFFECT OF HYPERBARIC OXYGEN ON Δ5-3β-HYDROXYSTEROID DEHYDROGENASE, 11- AND 18-STEROID HYDROXYLASES, AND ON NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE-LINKED DEHYDROGENASES IN ORGAN CULTURES OF RAT ADRENAL GLANDS
Authors: COUPLAND R. E. , BISWAS S. , MacDOUGALL J. D. B.
Published: December 2008

When organ cultures of rat adrenal glands are exposed to gaseous phases of air and hyperbaric oxygen at 2 atm., Δ5-3β-hydroxysteroid dehydrogenase is inactivated in both gaseous phases. During the first 24 hr., inactivation is more rapid in air but after 24 hr. little or no difference in rate is observed and little or no activity remains after 72 hr.

Estimates of 11- and 18-steroid hydroxylases after various periods of culture in the two gaseous phases and in the absence of exogenous substrate showed similar rates of inactivation during the first 24 hr. When progesterone was used as an exogenous substrate more enzyme activity remained after 24 hr. culture in hyperbaric oxygen than in air. Little enzyme activity remained after 72 hr.

The activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase and iso-citric dehydrogenase fall markedly when organ cultures of rat adrenal glands are incubated for 24 hr. in air and in hyperbaric oxygen at 2 atm.

The enzymes were, however, no more sensitive to hyperbaric oxygen than to air.
EFFECT OF DEFICIENT DIETS ON CORTICOSTEROID SYNTHESIS BY RAT ADRENALS IN VITRO AND ITS RELATIONSHIP TO INFECTIONS WITH NIPPOSTRONGYLUS BRASILIENSIS
Authors: CLARKE KAREN R.
Published: December 2008

Rats were fed on a low protein (LP) and a glucose—filter paper (GFP) diet; they were then infected with 1000 larvae of the nematode worm Nippostrongylus brasiliensis (Travassos, 1914) and killed 5 or 10 days later.

The adrenals of male and female rats on the GFP diet for 21 days showed atrophy and so did those of female rats on the LP diet for 42 or 56 days. The adrenals of male rats on the LP diet for 21 days were hypertrophic.

Referred to body weight, the adrenal weights of male rats on both diets were higher than those of the controls, the weights of the adrenals of female rats on the deficient diets were lower.

Adrenal weight and adrenal weight as a percentage of body weight were shown to bear no relationship to corticosteroid production in vitro, since the capacity for corticosteroid synthesis in vitro was increased in rats on the GFP diet only.

Significantly more parasites were found in the intestine after 5, but not after 10 days on both deficient diets suggesting that the deficient diets increased the susceptibility of the rats on initial contact with the parasite and before the development of acquired resistance. Later more parasites were lost by the rats on the deficient diets than from controls. These findings were not related to changes in the rate of corticosteroid synthesis.

The effects of stress, and the administration of cortisone or corticotrophin on host—parasite relationships is discussed in relation to the results of the present experiments. It is concluded that though these factors can increase susceptibility and lower acquired resistance, the effect on susceptibility can also be produced independently by severe dietary deficiency.
THE EFFECTS OF OESTRADIOL AND PROGESTERONE ON THE INCORPORATION OF TRITIATED URIDINE INTO THE GENITAL TRACT OF THE MOUSE
Authors: MILLER B. G. , EMMENS C. W.
Published: December 2008

The pattern of changes in levels of uridine incorporation into uterine and vaginal RNA at different times after the commencement of daily injections of several dose combinations of oestradiol and progesterone has been determined. Progesterone does not antagonize the response to oestradiol in the uterus and vagina at 16 hr., but in the uterus augments the effects of lower doses of oestradiol. At 48 hr., progesterone eliminates the response to oestradiol in the vagina. The interaction in the uterus is more complex. At 47 hr., or later, relatively high levels of uridine incorporation into uterine RNA are maintained by the administration of either oestradiol alone, at doses of 27 ng. or more; or by oestradiol and progesterone together, at doses of about 6 ng. and 0·33 mg. respectively. In mice receiving intraluminal peanut oil as a decidual stimulus the sensitivity of the uterus to deciduoma formation is not well correlated with its ability to incorporate uridine into RNA.
ACCUMULATION OF [14C]5-HYDROXYTRYPTAMINE IN THE PREGNANT RAT UTERUS AFTER TREATMENT WITH A MONOAMINE OXIDASE INHIBITOR
Authors: KOREN Z. , PFEIFER Y. , SULMAN F. G.
Published: December 2008

Intra-aortic injection of [3-14C]5-hydroxytryptamine creatinine sulphate ([14C]5-HT) into oestrogen or oestrogen-progestogen treated rats showed a pattern of homogeneous uptake similar to that found in untreated normal rats. In pregnant rats the injection resulted in a preferential uptake by the myometrium. Injection of a MAO inhibitor (pargyline hydrochloride, Eutonyl) into the amniotic sac, preceding the [14C]5-HT injection by 30 min., changed this pattern to a preferential accumulation in the myometrium and the spleen, perhaps due to unhampered transport of preserved 5-HT by the thrombocytes to the spleen. When [14C]5-HT was injected i.p. into the foetuses they retained high amounts of exogenous 5-HT. Myometrium and placenta also showed increased 5-HT uptake.

This finding—taken together with the established fact that foetal 5-HT increases and placental monoamine oxidase decreases steadily up to term—suggests that at term the release of foetal 5-HT may enrich the maternal myometrium with 5-HT through the umbilical arteries without its entering the general blood circulation. It is also possible that additional maternal 5-HT may accumulate in the myometrium sensitized by the oestrogen surge at term. The importance of these mechanisms for the induction of labour is discussed.
A QUANTITATIVE IMMUNOLOGICAL ASSAY FOR PREGNANT MARE SERUM GONADOTROPHIN
Authors: ALLEN W. R.
Published: December 2008

Rabbits and turkeys were immunized against commercial preparations of pregnant mare serum gonadotrophin (PMSG). Ouchterlony double diffusion and haemagglutination-titration tests showed that the rabbit antisera contained non-specific antibodies against horse serum proteins, whereas the turkey antisera did not. Both types of antisera neutralized the effects of PMSG in vivo. One specific turkey anti-PMSG serum was used unabsorbed to establish a sensitive and accurate haemagglutination—inhibition assay for PMSG in equine serum and in saline. Pyruvic aldehyde-treated sheep red blood cells sensitized with PMSG were used in perspex haemagglutination trays. The reliability criteria of the assay is discussed. The smallest quantity of PMSG detectable in saline was 0·3 i.u./ml.

The turkey anti-PMSG serum showed a strong immunological cross-reaction with preparations of equine pituitary follicle-stimulating hormone (FSH) and equine pituitary luteinizing hormone (LH), a faint reaction with human pituitary gonadotrophin and no reaction against human chorionic gonadotrophin, ovine FSH, ovine LH, bovine LH or porcine FSH.
PROGESTERONE WITHDRAWAL AS THE LACTOGENIC TRIGGER IN THE RAT
Authors: KUHN N. J.
Published: December 2008

Lactogenesis, as indicated by the appearance of mammary lactose, follows ovariectomy and/or hysterectomy and the fall in the concentration of progesterone in the plasma preceding normal parturition in the pregnant rat. It is suppressed by administered progesterone in all cases, and by prolactin after hysterectomy.

The natural lactogenic signal may occur 30 hr. before parturition, due to conversion of progesterone to 20α-hydroxypregn-4-en-3-one in the ovaries. Changes in the concentration of corticosterone, oestrogen and prolactin in the plasma either do not occur or do not constitute a lactogenic signal.
THE EFFECT OF A HIGH-CARBOHYDRATE DIET ON GLUCOSE, INSULIN SENSITIVITY AND PLASMA INSULIN IN RATS
Authors: BLÁZQUEZ E. , QUIJADA CLEMENTE LOPEZ
Published: December 2008

When groups of rats were kept on control and high-carbohydrate diets from the end of lactation until their body weight reached 150 g. it was found that the animals fed on the high-carbohydrate diet gained weight more rapidly, with an increase in fat deposits.

Glucose and plasma insulin in both groups were compared with the amounts of hormone extracted from their pancreases. When the rats on the control diet were killed the insulin and glucose plasma levels were 40 ± 3 μu./ml. and 156·69 ± 13 mg./100 ml. respectively. After 17–20 hr. fasting these values decreased significantly (P < 0·01) to 18 ± 1·5 μu./ml. and 116 ± 13 mg./ml. The amount of insulin in the pancreas was not modified by fasting. In the rats fed on the high-carbohydrate diet the plasma insulin and glucose values were higher than those in the control rats (50 ± 3·8 μu./ml. and 187 ± 19 mg./100 ml.); after 17–20 hr. starvation the glucose levels were reduced and the plasma insulin concentration remained higher (44 ± 2·9 μu./ml.); the insulin content of the pancreas was higher than in the control rats. In vitro the epididymal fat and the diaphragm of the rats on the high-carbohydrate diet were less sensitive to insulin than the same tissues in the controls.
A STUDY OF THE HETEROGENEITY OF PARATHYROID HORMONE PREPARATIONS
Authors: LEA D. J. , ZANELLI J. M.
Published: December 2008

Bovine parathyroid glands, stored in several ways, have been extracted by published methods using urea and HCl, or phenol, and recent modifications of the latter method utilizing mercaptoethanol. The extracts were purified by gel filtration. Parathyroid hormone of high potency has been obtained only from rapidly frozen glands by the method using phenol and mercaptoethanol.

Purified hormone preparations were extremely heterogeneous, were indistinguishable from material of much lower potency by gel electrophoresis, and shared common antigenic determinants with components of fractions having insignificant biological activity. It is possible that parathyroid hormone which has been modified irreversibly at the biologically active site is commonly present in gland extracts.
ULTRASTRUCTURAL CHANGES IN THE ADENOHYPOPHYSIS OF HYPOTHYROID RABBITS
Authors: FOSTER C. L. , CAMERON E. , YOUNG B. A.
Published: December 2008

The ultrastructure of the adenohypophysis of the rabbit, after treatment with propylthiouracil, is described. All cells in the zona tuberalis and pars distalis proper, with the exception of the prolactin producing (type 1) and stellate cells (type 5), were affected. However, the only ones which presented some evidence of sequential changes were the type 4 cells. These became markedly degranulated and sometimes showed vesiculation of the cisternae of the granular endoplasmic reticulum, similar to that observed in the 'thyroidectomy' cells in some other species. Although changes occurred in the somatotrophs (type 2) and in the gonadotrophs (type 3) the evidence suggests that it is the type 4 cells which have a thyrotrophic function.
THE INFLUENCE OF SOME PROGESTOGENS ON THE MAMMARY GLAND OF THE FOETAL MOUSE DURING THE PERIOD OF INITIAL DIFFERENTIATION
Authors: CUPCEANCU B. , NEUMANN F. , ULLOA A.
Published: December 2008

Progestogens administered to pregnant mice during the initial period of differentiation of the mammary gland rudiment produced various morphological changes in the mammary rudiments of both male and female foetuses.

Norethisterone (17α-ethynyl-Δ4-oestrene-17β-ol-3-one) caused virilization of the rudiments in female foetuses. Medroxyprogesterone acetate (6α-methyl-Δ4-pregnene-17α-ol-3,20-dione-17α-acetate) produced virilization of the rudiments in female and feminization in male foetuses. Gestonorone caproate (19-nor-Δ4-pregnene-17α-ol-3,20-dione-17α-caproate) and allyloestrenol (17α-allyl-Δ4-oestren-17β-ol) tended to cause feminization of some of the mammary rudiments.

Androgenic, anti-androgenic or anti-gonadotrophic effects of the investigated substances are considered as possible mechanisms involved in the present findings.
THE OESTROGENIC POTENCY IN THE MOUSE OF SEVERAL SUBSTANCES CLOSELY RELATED TO DIETHYLSTILBOESTROL AND MESO-HEXOESTROL
Authors: MILLER B. G. , EMMENS C. W.
Published: December 2008

The effects of oestradiol, diethylstilboestrol, α,α′-dimethylstilbene-4,4′-diol (DMS), α-ethyl-α′-methylstilbene-4,4′-diol (MES), meso-hexoestrol, dl-hexoestrol, meso-butoestrol, dl-butoestroland erythro-α-ethyl-α′-methyl-4,4′-dihydroxybibenzyl (erythro-MEA) on the incorporation of tritiated uridine into uterine RNA were investigated. At 2 hr., valid relative potency estimates with oestradiol were obtained with all substances, and MES, erythro-MEA and meso-butoestrol were almost as potent as diethylstilboestrol and meso-hexoestrol. The time-course of the uridine response to the different substances varied markedly. Injections every 16 hr. of DMS, MES, dl-hexoestrol, meso-butoestrol and erythro-MEA elicited little uterine or vaginal growth, but small doses of these substances given every 4 hr. elicited considerable growth in both organs. It was concluded that the compounds tested were oestrogens and not pro-oestrogens.
HORMONE SECRETION DURING EARLY PREGNANCY IN THE MOUSE
Authors: FINN C. A. , MARTIN L.
Published: December 2008

The distribution of cell division in the tissues of the mouse uterus changes in a characteristic manner during the first few days of pregnancy due to changes in the secretion of ovarian hormones. Pregnant mice were ovariectomized at various times and attempts made to reproduce the pattern of cell division with exogenous hormones. The schedule of hormone injections producing a pattern of uterine mitoses which most closely approached that of pregnancy suggested that secretion of both oestrogen and progesterone started about 48 hours after mating and continued, possibly increasing, until after implantation had started. This conflicts with the oestrogen surge hypothesis. Further experiments were carried out to determine the optimum hormone treatment schedules for sensitivity to induction of the oil decidual cell reaction. Multiple small doses of oestradiol allowed the production of greater deciduomas than a single dose, thus again suggesting that the oestrogen surge hypothesis may not be correct.
FURTHER STUDIES ON THE RELATIONSHIP BETWEEN C19- AND C21-STEROID SYNTHESIS IN THE HUMAN ADRENAL GLAND
Authors: CAMERON E. H. D. , JONES T. , JONES D. , ANDERSON A. B. M. , GRIFFITHS K.
Published: December 2008

As part of a continuing study of adrenal steroids in relation to breast cancer, various experiments were performed in order to study relationships between androgen and corticosteroid biosynthesis. Chopped tumour tissue from a 'mixed cell' adrenal adenoma (7·4 g.) removed from a patient in Cardiff Royal Infirmary was incubated with [4-14C]pregnenolone and [7α3H]17α-hydroxypregnenolone for periods of time ranging from 30 to 120 min. The results of this work suggest that 17α-hydroxyprogesterone may not be an obligatory intermediate in androgen or cortisol synthesis. Evidence from further experiments with 'normal' human adrenal tissue removed from breast cancer patients using previously established ultramicrochemical techniques indicates that dehydroepiandrosterone (DHA) sulphokinase enzyme system is confined to the zona reticularis of the gland. The conversion of [7α-3H]DHA sulphate, [7α-3H]androstenedione and [7α-3H]testosterone to oestrogens and their conjugates by adrenal homogenates was also investigated. Conversions were extremely low from all precursors.
THE EFFECT OF VALINOMYCIN ON THE TOAD BLADDER: ANTAGONISM TO VASOPRESSIN AND ALDOSTERONE
Authors: BENTLEY P. J.
Published: December 2008

The macrolide antibiotic valinomycin decreased short-circuit current (SCC, Na transport) across the isolated bladder of the toad. This effect was not overcome by increasing the K+ levels in the bathing medium or by the action of amphotericin B.

The effects of vasopressin on both sodium and water transfer across the toad bladder were inhibited by valinomycin and the latter inhibition is non-competitive. The action of theophylline in increasing water transfer across the bladder was also inhibited. Cyclic AMP also increased water and Na+ transfer across the bladder but its action was not reduced by the macrolide. These results suggest that valinomycin inhibits adenyl cyclase.

Aldosterone increases sodium transport across the toad bladder and this action was abolished by previous incubation of the tissue with the macrolide. Once the steroid-induced effect had been established subsequent addition of valinomycin did not alter the sodium transfer.

Valinomycin thus appears to have several sites of action on the toad bladder.
STEROIDOGENESIS AND MORPHOLOGY OF HUMAN OVARIAN CELL TYPES IN TISSUE CULTURE
Authors: CHANNING CORNELIA P.
Published: December 2008

Human granulosa, thecal, and stromal cells were grown in tissue culture in a medium containing 15% pooled human male serum, 30% Parker's medium '199', and 55% Hanks's solution. Granulosa cells underwent hyperplasia until about 10–12 days of culture and stayed alive up to at least 100 days. However, from about 20 days onward some of the cells gradually became detached from the glass. Initially the cytoplasm became eosinophilic and granular and accumulated lipid droplets and maintained these characteristics for about 20 days. From day 0–3 of culture, cells from non-gonadotrophin-treated women secreted 10·7 μg. progesterone, 0·54 μg. pregnenolone, 0·52 μg. oestrone and 0·45 μg. oestradiol as determined by gas-liquid chromatography. They also converted pregnenolone to similar products.

A pool of thecal cells cultured for 3 days secreted 2·84 μg. progesterone, 0·36 μg. pregnenolone, 1·38 μg. 17-hydroxyprogesterone, 2·10 μg. androstenedione, 1·93 μg. oestrone and 1·44 μg. oestradiol. Stromal cells secreted less steroid per cell and no detectable oestrogens. Thecal cells grew in stellate colonies and had a lacy cytoplasm which contained vacuoles of various sizes which did not contain large amounts of lipid. Stromal cells resembled fibroblasts in morphology and growth characteristics.
OESTROGEN RESPONSES OF RATS NEONATALLY STERILIZED WITH STEROIDS
Authors: WRENN T. R. , WOOD JOAN R. , BITMAN J.
Published: December 2008

At 75 days of age, female rats neonatally sterilized with oestradiol benzoate or testosterone propionate were compared with normal and ovariectomized rats with regard to their 6-hr. response to 0·2 μg. oestradiol 17β. The greatest increases in uterine weight, glucose and glycogen concentrations and per cent uterine water occurred in the ovariectomized animals. A marked oestrogen response also occurred in the animals neonatally sterilized with oestradiol benzoate. The response of the normal rats was slight, and the testosterone propionate-treated rats were the least affected.

Adrenal, pituitary, and ovarian weights were found to be affected by the neonatal hormone treatments. Vaginal patency was completely inhibited in the rats injected with testosterone propionate. It is concluded that rats neonatally sterilized with steroids are much less suitable than ovariectomized animals for oestrogen assays.
OESTROGENIC AND ANTIOESTROGENIC ACTIVITIES OF A NUMBER OF STEROIDS IN BEHAVIOURAL OESTRUS AND VAGINAL SMEAR ASSAYS IN THE EWE
Authors: LINDSAY D. R. , SCARAMUZZI R. J.
Published: December 2008

Fourteen synthetic steroids and androstenedione were examined in ovariectomized ewes for oestrogenic activity when administered alone and with oestradiol benzoate by intramuscular injection. None of the compounds investigated was active when administered alone, as assessed by the vaginal smear assay, and only androstenedione produced a behavioural response. Androstenedione had a MED of 8·8 mg. but was less active when administered intravenously. Several steroids acted as anti-oestrogens when injected with oestradiol benzoate. Eight steroids inhibited the behavioural response and four the vaginal response. An additive response was found with androstenedione for behavioural response and with 17β-ethyl-17-hydroxy-19-nor-4-androsten-3-one (SC-5914) for vaginal response.

Vaginal and behavioural responses were not necessarily related, and responses obtained in the ewe to particular steroids were not identical with those obtained in laboratory animals by other workers using similar tests.
THE PINEAL ORGAN: PHOTOPERIOD AND REPRODUCTIVE CYCLES IN THE GOLDFISH, CARASSIUS AURATUS L.
Authors: FENWICK J. C.
Published: December 2008

The possible endocrine role of the pineal organ was studied in goldfish. Pinealectomized, sham-pinealectomized and intact goldfish were exposed to various artificially-maintained light regimens during different times of the year and the effects on gonad weight were observed. In addition, the thyroidal and interrenal tissues, the plasma osmotic concentration, and the plasma levels of Ca2+, Na+ and Cl− ions were studied in some of the experiments.

The mean gonosomatic index (GSI = gonad weight expressed as percentage of body weight) of goldfish varied throughout the year and was greatest during the month of May. Further, the response of the gonads to increased daily light exposure (e.g. 16 hr. of light and 8 hr. of darkness as opposed to 8 hr. of light and 16 hr. of darkness) was maximal during the 3 months immediately preceding May. These results indicate that whilst gonadal maturation in goldfish is influenced by photoperiod, the efficacy of an increased light—dark ratio in stimulating gonadal maturation is subject to the time of year that it is imposed.

An effect of pinealectomy on goldfish gonad size was restricted to those animals pinealectomized prior to, and held throughout the months of increased gonadal responsiveness to prolonged light (i.e. January, February, March, April and May). During these months, pinealectomized animals underwent greater gonadal development than sham-pinealectomized or intact goldfish when all experimental groups were exposed to 8 hr. light/day.

The thyroidal and interrenal tissues, plasma osmotic concentration, and the plasma levels of Ca2+, Na+, and Cl− ions were not affected by pinealectomy in any of the experiments in which these parameters were tested.

The pineal organ of the goldfish was found to be specifically related to gonadal size and this relationship was associated with the responsiveness of the gonads to light.
THE INTERFERENCE OF FREE AND ESTERIFIED CHOLESTEROL IN THE SPECTROFLUORIMETRIC MEASUREMENT OF PLASMA 11-HYDROXYSTEROIDS
Authors: STENLAKE J. B. , DAVIDSON A. G. , WILLIAMS W. D. , DOWNIE W. W.
Published: December 2008

Cholesterol and cholesterol esters have been identified on the basis of thin-layer and gas—liquid chromatographic data and fluorimetric characteristics as major interfering fluorogens in a simple fluorimetric method for determining plasma corticosteroids.

In a small series of normal subjects the average concentration of fluorogen, which was not 11-hydroxysteroid, was 3·4 μg. apparent cortisol/100 ml. plasma, equivalent to 22·4% of the total fluorogen present.
THE DEVELOPMENT OF A RADIOIMMUNOASSAY FOR OXYTOCIN: RADIO-IODINATION, ANTIBODY PRODUCTION AND SEPARATION TECHNIQUES
Authors: CHARD T. , KITAU M. J. , LANDON J.
Published: December 2008

A simple and rapid method is described for labelling oxytocin with 131I at a high specific activity. This method is compared with those of previous workers. A satisfactory antiserum has been raised by direct intra-lymph node injection of oxytocin adsorbed to carbon microparticles. A number of methods for separating antibody-bound from free oxytocin are described, and reasons given for preferring a procedure using ammonium sulphate precipitation. These data form the basis for developing a radioimmunoassay intended for the determination of oxytocin in human plasma.
CAUSE OF INCREASED PLASMA CONCENTRATION OF IODOTYROSINES IN GRAVES' DISEASE
Authors: FÖLDES J. , TAKÓ J. , BÁNOS C. , GESZTESI E. , VARGA I.
Published: December 2008

In most cases of Graves' disease the level of iodotyrosines in the plasma is above normal. With a view to ascertaining the cause of this phenomenon simultaneous determinations were made of the iodotyrosine and long-acting thyroid stimulator (LATS) levels in the plasma and of the titre of thyroid antibodies. It was found that high plasma concentrations of iodotyrosines in exophthalmic goitre were mainly due to auto-immune thyroiditis, but that LATS may also contribute to the phenomenon.
EFFECTS OF OVARIECTOMY AND OVARIAN HORMONES ON RNA BASE RATIOS IN SPECIFIC RABBIT BRAIN AREAS
Authors: ELEFTHERIOU B. E. , DESJARDINS C. , PATTISON M. L.
Published: December 2008

The ribonucleic acid (RNA) base percentages were estimated in the hypothalamus, amygdala, hippocampus, frontal cortex, cerebellum and spinal cord of adult intact female rabbits, and after ovariectomy followed by replacement therapy with oestradiol-17β, progesterone and oestradiol plus progesterone. The results indicate a lack of effect on the spinal cord, but a variable effect on all other brain regions examined. In response to the various treatments, all regions examined produced RNA very rich in guanosine monophosphate indicating synthesis of specific RNA. The hypothalamus showed the most significant overall changes. Progesterone injections resulted in the most persistent effects of the hormonal treatments employed. Hypotheses are proposed to explain the variable hormonal effects on brain RNA base composition. It is suggested that ovarian hormones produce specific molecular changes in nervous tissue related either to 'receptors' for the hormones or to neural functions related to behavioural phenomena which are mediated by these hormones.
HORMONAL REQUIREMENTS FOR THE MAINTENANCE OF OESTRADIOL-INDUCED INHIBITION OF UTERINE SENSITIVITY IN THE OVARIECTOMIZED RAT
Authors: MEYERS K. P.
Published: December 2008

Ovariectomized rats treated with 2·5 or 5·0 mg. progesterone daily received a single subcutaneous injection of 0·2 μg. oestradiol on the third day of the progesterone treatment. The deciduomal response to trauma by endometrial scratching was used to determine the degree of uterine sensitivity at various times after oestradiol. Uterine sensitivity was partially and then completely lost 36 and 48 hr. after oestradiol administration. The inhibition of uterine sensitivity persisted until 9 and 11 days after oestradiol when the animals received 2·5 and 5·0 mg. progesterone daily. Uterine sensitivity was completely inhibited on day 11 with doses of oestradiol from 0·2 to 0·05 μg. Withdrawal of progesterone treatment for 48 or 72 hr., but not for 24 hr., after oestradiol treatment restored uterine sensitivity. These results show that the oestradiol-induced inhibition of uterine sensitivity in the progestational endometrium is maintained by continuous progesterone treatment and that the duration of this effect is dependent on the dose of progesterone given.
THE RADIOAUTOGRAPHIC LOCALIZATION OF 125I-LABELLED BOVINE PARATHYROID HORMONE
Authors: DE KRETSER D. M. , MARTIN T. J. , MELICK R. A.
Published: December 2008

The distribution and localization of 125I-labelled bovine parathyroid hormone was studied by radioautography in adult rats. The principal site of localization was the proximal convoluted tubule of the kidney. Light and variable localization was present in the liver, but no significant amount of label was found in muscle, spleen, bone or articular cartilage. The localization of this labelled compound in the proximal convoluted tubule suggests that this region degrades 125I-labelled parathyroid hormone.
THE EFFECTS OF PROLONGED STARVATION AND REFEEDING ON 24-HR. URINARY INSULIN LEVELS IN OBESE SUBJECTS
Authors: HELLIER M. D.
Published: December 2008

Six obese patients, three men and three women, underwent a period of prolonged total starvation with subsequent refeeding. During starvation 24 hr. urinary insulin excretion fell in five of the six patients, and reached abnormally low values in four. On refeeding there was an immediate rise in urinary insulin excretion in all the patients and in four abnormally high levels were reached. After the initial rise the amounts of urinary insulin again fell despite continued and increasing calorie intake, and in three patients returned to the previously low levels. It is suggested that on refeeding there is preferential release of recently formed 'pro-insulin' from a pancreas depleted of normal insulin stores by starvation, and that restoration of a normal pattern of insulin secretion can occur only after normal pancreatic insulin stores have been repleted. A striking difference in response to starvation was observed between men and women.
PLASMA TESTOSTERONE LEVELS IN MALES WITH THE 47,XYY KARYOTYPE
Authors: PRICE W. H. , VAN DER MOLEN H. J.
Published: December 2008

No difference could be demonstrated between the plasma testosterone levels in 17 males with the 47,XYY karyotype and appropriately selected controls.

Significantly higher levels of testosterone were recorded in both 47,XYY and 46,XY males at the maximum security hospital than in males with both karyotypes in other hospitals and in the general population.
ACID PHOSPHATASE ACTIVITY IN VIABLE AND REGRESSING RAT CORPORA LUTEA
Authors: SMITH JEANNE A. , WAYNFORTH H. B.
Published: December 2008

Free and total acid phosphatase activity has been measured in individual corpora lutea from rat ovaries in various reproductive states (both natural and experimentally induced). Significant changes both in weight and enzymic activity were found, and an attempt has been made to correlate these with the growth and regression of the corpora lutea. A possible connexion between acid phosphatase activity, progesterone secretion and/or cellular composition of the corpus luteum is suggested.
AFFERENT PATHWAYS OF STRESSFUL STIMULI: CORTICOTROPHIN RELEASE AFTER HYPOTHALAMIC DEAFFERENTATION
Authors: MAKARA G. B. , STARK E. , PALKOVITS M.
Published: December 2008

Corticotrophin (ACTH) release induced by stressful stimuli has been studied in rats with completely deafferentated medial basal hypothalamus (MBH) pituitary islands or median eminence (ME)-stalk pituitary islands. The plasma corticosterone level was used as index of ACTH release.

In rats with MBH pituitary islands, capsaicin failed to raise the plasma corticosterone level, but the intraperitoneal administration of E. coli endotoxin, histamine, insulin or a large subcutaneous dose of formaldehyde caused ACTH release which could not be distinguished from that in the controls. Histamine and insulin induced ACTH release even in rats with a ME-stalk pituitary island.

It is suggested that E. coli endotoxin, histamine, insulin hypoglycaemia and large doses of formaldehyde may be classified as 'humoral' stimuli of ACTH release, since a neural afferent input to the MBH is not essential for their action. On the other hand, the integrity of some neural pathways to the MBH is essential for the ACTH-releasing effect of capsaicin.
INFLUENCE OF METHYLTESTOSTERONE AND CYPROTERONE ACETATE ON WOLFFIAN DUCT DIFFERENTIATION IN FEMALE RAT FOETUSES
Authors: ELGER W. , STEINBECK H. , CUPCEANCU B. , NEUMANN F.
Published: December 2008

In contrast to results in rabbit and dog foetuses, Wolffian duct stabilization in male rat foetuses was inhibited by cyproterone acetate. On the other hand, the stabilizing effect of methyltestosterone in female rat foetuses could be abolished even when excessive androgen doses were given. The hormonal factor(s) involved in normal Wolffian duct stabilization in male rat foetuses remains to be clarified.
THE MECHANISM OF ACTION OF GONADOTROPHIC HORMONES IN AMPHIBIANS: THE STIMULATION OF Δ5-3β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN TESTES OF XENOPUS LAEVIS DAUDIN
Authors: WIEBE J. P.
Published: December 2008

The effects of gonadotrophins on the Δ5-3β-hydroxysteroid dehydrogenase (3β-HSD) activity in testes of Xenopus laevis have been determined by histochemical and spectrophotometric methods. Methallibure was employed to inhibit the activity of endogenous pituitary gonadotrophins. Injections of pregnant mare serum gonadotrophin (PMS), human chorionic gonadotrophin (HCG), follicle stimulating hormone (FSH), or luteinizing hormone (LH) resulted in pronounced increases in 3β-HSD activity in the microsomal fraction. PMS was the most stimulatory; the injection of 250 i.u. resulted in an almost ten fold increase in activity. PMS and HCG were more effective than FSH and LH in stimulating 3β-HSD activity and PMS and FSH were more effective than HCG and LH respectively. The increases in activity were inhibited by concomitant injections of actinomycin. 3β-HSD activity was not stimulated directly by gonadotrophins in vitro, but another dehydrogenase or group of dehydrogenases appeared to be activated directly by HCG, FSH and LH but not by PMS. The results are discussed in relation to findings in mammals.
AN EVALUATION OF THE METHOD OF COX FOR THE RAPID ANALYSIS OF PREGNANEDIOL IN URINE BY GAS—LIQUID CHROMATOGRAPHY
Authors: BARRETT SUSAN A. , BROWN J. B.
Published: December 2008

Cox's method for the analysis of pregnanediol in human urine by gas—liquid chromatography (GLC) of the free steroid on neopentyl glycol adipate in conjunction with a semi-automatic extractor for processing the urine was evaluated. Without automation of the GLC, one worker could complete 24 assays/day. The reliability of Cox's method was confirmed. Results obtained throughout the menstrual cycle in 15 women, during the pregnancies of 480 patients, in 18 postmenopausal women and in 20 men are presented.
THE ROLE OF OESTROGENS IN SPONTANEOUS OVULATION: EVIDENCE FOR POSITIVE OESTROGEN FEEDBACK IN THE 4-DAY OESTROUS CYCLE
Authors: LABHSETWAR A. P.
Published: December 2008

A possible involvement of oestrogens in regulating the ovulatory release of luteinizing hormone (LH) has been explored by using an oestrogenantagonist, clomiphene. When given orally in the afternoon on the day before pro-oestrus to rats with a 4-day cycle, the compound prevented ovulation on the morning of oestrus. This was not associated with interference with vaginal cornification, uterine ballooning or mating. Similarly, clomiphene prevented ovulation in hamsters when given at a corresponding stage of the cycle. In adult rats ovulation could be fully restored by the intravenous administration of LH or LH releasing factor at 14.00 hr. on the day of pro-oestrus. Oestradiol benzoate given simultaneously with clomiphene on the day before pro-oestrus or the stimulus provided by mating on the night of pro-oestrus were also effective in this respect. It is implicit in these findings that clomiphene interferes with ovulation by virtue of its anti-oestrogenicity. This indicates that a positive feedback of oestrogen is an integral part of the chain of events culminating in the ovulatory release of LH in the reproductive cycle.
CORTISOL UTILIZATION BY SALIVARY GLAND, KIDNEY AND ADRENAL CORTEX
Authors: FERGUSON M. M. , GLEN J. B. , MASON D. K.
Published: December 2008

Cortisol utilization by salivary glands, kidneys and adrenals of various mammals has been compared by using a standard histochemical technique for the demonstration of hydroxysteroid dehydrogenases. 11β-Hydroxysteroid dehydrogenase activity was localized in salivary gland ducts, renal collecting and convoluted tubules and in the adrenal cortex of some species. There was no obvious relationship between the levels of enzyme activity in the salivary glands, kidneys and adrenals. Neither was the presence of 11β-hydroxysteroid dehydrogenase in salivary glands particularly associated with mucous or serous secretion, nor were sex differences in levels of activity evident.
THE SYNTHESIS OF DNA AND RNA IN NORMAL HUMAN ENDOMETRIUM IN SHORT-TERM INCUBATION IN VITRO AND ITS RESPONSE TO OESTRADIOL AND PROGESTERONE
Authors: NORDQVIST S.
Published: December 2008

A method is described for short-term incubations in vitro of normal endometrium for the study of nucleic acid synthesis. Tissue suspensions of specimens obtained at curettage were incubated with and without hormones in a medium consisting of Parker's 199 medium and 20% adult human serum; [3H]thymidine and [14C]uridine were added. The isotope uptake into the nucleic acids was determined and related to the total amount of DNA in each sample. Marked variation in DNA synthesis was noted in endometria obtained at different phases of the menstrual cycle. RNA synthesis varied less. After the addition of progesterone, synthesis of both nucleic acids was reduced. The magnitude of this response varied in different endometria. Thus DNA synthesis in endometria already under strong progesterone influence in vivo (midsecretory phase) was least affected when progesterone was added in vitro.
INTERACTIONS OF OESTRADIOL AND PROGESTINS IN THE MOUSE UTERUS
Authors: MARTIN L. , FINN C. A.
Published: December 2008

Progesterone and norgestrel did not inhibit uterine weight increases produced by single injections of oestradiol-17β but reduced those produced by three injections. Histological studies indicate that this anomaly is due to changes in uterine sensitivity to oestradiol, after the first injection of oestradiol.

In ovariectomized animals not receiving a progestin a second or third injection of oestradiol stimulated further increases in stromal and epithelial growth and produced final uterine weights which were large compared with those produced by a single injection.

After pretreatment with a progestin, the first injection of oestradiol produced stromal hypertrophy and hyperplasia but a second and third did not. This is due to a refractory state which develops in the stroma after the first injection, and which is prolonged by the second. Thus the final uterine weights were similar whether single or multiple injections of oestradiol were given.

It is suggested that the anti-oestrogenic effects of progestins in uterine weight assays result from the refractory state induced by oestrogen.