bluuebunny/crossref_metadata_2025 huggingface dataset:
THE KINETICS OF OESTRADIOL-17β METABOLISM IN THE SHEEP
Authors: CHALLIS J. R. G. , HARRISON F. A. , HEAP R. B.
Published: December 2008

The metabolic clearance rate of oestradiol-17β from whole blood and its conversion to oestrone and oestradiol-17α were measured in pregnant and non-pregnant (cyclic, lactating and anoestrous) sheep using tracer kinetic techniques. The metabolic clearance rate was much the same in sheep in different reproductive states (mean in all animals (±s.e.m.) = 2·449 ± 0·155 1/min). The highest values were reached on days 143–145 of pregnancy (3·287 ± 0·3351/min). The mean conversion ratio of oestradiol-17β to oestrone was 17·0 ± 2·2%, and that of oestradiol-17β to oestradiol-17α was 14·1 ± 1·1%. The production rate of oestradiol-17β increased from 0·007 to 0·103 μg/min up to 3 days before parturition to 0·035–1·257 μg/min during the last 12 h of pregnancy.

During the continuous infusion of [3H]oestradiol-17β and when a steady state had been reached, approximately 20–30% of the radioactivity in whole blood could be extracted with ether. Of this radioactivity more than 90% was attributable to labelled oestradiol-17β, oestrone and oestradiol-17α in jugular blood, though only about 70% could be accounted for as these oestrogens in uterine venous blood.
IDENTIFICATION AND MEASUREMENT OF SULPHATE-CONJUGATED NEUTRAL STEROIDS IN THE INTESTINAL CONTENTS OF EARLY AND MID-TERM FOETUSES
Authors: HUHTANIEMI I. , VIHKO R.
Published: December 2008

Sulphate-conjugated neutral steroids in the intestinal contents of early and mid-term human foetuses (14–20 weeks of gestation) were investigated by gas—liquid chromatography and gas chromatography—mass spectrometry. Twenty-four neutral steroids were found in the monosulphate fraction and 21 in the disulphate fraction. The total concentration of these steroids varied between 9·6 and 15·3 mg/100 g meconium wet weight, about half being monosulphates and half disulphates. Steroids with a 3β-hydroxy-5-ene structure were found and also saturated steroids which carried hydroxyl groups at carbons 3, 11, 15, 16, 17, 18, 19, 20 or 21. Among them were steroids not previously detected in human foetal compartments. Thus, the foetal meconium is both qualitatively and quantitatively the richest foetal source of neutral steroid sulphates so far investigated.

The present results together with those reported in the literature show that in the course of pregnancy there is a many-fold increase in the steroid concentration of the foetal intestinal contents. This is most obvious in the case of saturated C19 steroids and polar pregnane derivatives. Reduction of the 20-ones to 20β-ols seems to be more extensive towards the end of pregnancy. 5, 16-Pregnadienes and 3β-hydroxy-5β-pregnanes are present in higher concentrations in early pregnancy.
EFFECT OF OVARIAN HORMONES AND SYNTHETIC PROGESTINS ON VAGINAL SIALIC ACID IN THE RAT
Authors: GALLETTI F. , GARDI R.
Published: December 2008

Total amount and concentration of vaginal sialic acid were determined in rats after ovariectomy and treatment with oestradiol, progesterone, norethindrone acetate and quingestanol acetate. Sialic acid concentration increased after ovariectomy and decreased after subsequent treatment with oestradiol. Progesterone had no effect on sialic acid concentration in spayed rats. The synthetic progestins norethindrone acetate and quingestanol acetate, given orally, showed a diphasic effect, increasing vaginal sialic acid concentration at low doses and decreasing it at higher doses. These results are discussed in the light of the oestrogenic properties of progestins derived from 19-nortestosterone.
PROLACTIN PRODUCTION AND LACTOGENESIS IN RATS AFTER OVARIECTOMY IN LATE PREGNANCY
Authors: SIMPSON A. A. , SIMPSON M. H. W. , KULKARNI P. N.
Published: December 2008

Ovariectomy on day 17 of pregnancy in rats that normally give birth on day 23 induced lactogenesis and foetal resorption but did not alter the pattern of change in pituitary or plasma prolactin concentration. Plasma prolactin levels increased significantly in both ovariectomized and sham-operated animals from days 18–22 of pregnancy. This suggests that factors other than ovarian products control the rise in late pregnancy of plasma prolactin in the rat. The results support earlier reports that progesterone withdrawal may be the lactogenic trigger in the rat.
EFFECT OF PERPHENAZINE DURING LATE PREGNANCY ON PROLACTIN PRODUCTION AND LACTOGENESIS IN THE RAT
Authors: SIMPSON A. A. , SIMPSON M. H. W. , KULKARNI P. N.
Published: December 2008

Perphenazine given on day 18 of pregnancy and each day following caused large increases in plasma prolactin levels in rats as measured on days 19–23. Pituitary prolactin was depleted on day 19, but subsequently returned to slightly above control values. Adrenal weight was significantly increased by perphenazine treatment suggesting increased production of adrenocorticotrophin and glucocorticoids. The increased prolactin levels caused no significant change on any day in either mammary lactose, glucose, RNA or DNA concentrations or the RNA:DNA ratio. The findings support earlier reports that an increased level of plasma prolactin during pregnancy does not by itself induce lactogenesis in the rat.
OESTRONE METABOLISM IN PREGNANT AND LACTATING GOATS
Authors: CHALLIS J. R. G. , LINZELL J. L.
Published: December 2008

Since blood oestrogen levels are much higher during pregnancy in the goat than in the sheep a continuous isotope infusion technique was used to study oestrone metabolism in five experiments on two goats during late pregnancy and early lactation. The metabolic clearance rate was similar to that in the sheep in all experiments (mean value ± s.e.m., 4·02 ± 0·25 1/min); therefore the high blood oestrone concentrations in late pregnancy (851–2043 pg/ml) were due to high oestrone production rates (4·22–7·54 μg/min). There was some conversion of oestrone to oestradiol-17β by the mammary glands and other tissues (mean conversion ratio 17·1%) and a little (< 10%) binding of oestrone to erythrocytes. The uptake of oestrone by the mammary gland corresponded to < 3% of the total production rate. These results are compared with those obtained for other steroid hormones (progesterone, cortisol) in the goat and sheep.
THE EFFECT OF HYPOTHALAMIC DEAFFERENTATION UPON THE ULTRASTRUCTURE AND HORMONE CONTENT OF THE PARAVENTRICULAR NUCLEUS
Authors: DYER R. G. , DYBALL R. E. J. , MORRIS J. F.
Published: December 2008

The ultrastructure and hormone content of the paraventricular nucleus was studied in female rats after surgical isolation of the hypothalamus (by preparation of hypothalamic islands) from the rest of the brain for 48 h. When compared with control animals no quantitative changes were observed in the proportion of cytoplasm occupied by endoplasmic reticulum, Golgi apparatus and mitochondria or in the number of lysosomes/100 μm2 of cytoplasm. However, there was a very significant (P < 0·001) increase in the number of neurosecretory granules observed in the perikarya of paraventricular cells in the deafferentated preparations.

Bioassay of hypothalamic extracts for milk ejection and antidiuretic activities showed that there was a significant increase (P < 0·05) of the former in hypothalamic islands. The increase was greatest in the paraventricular region (P < 0·01). The hypothalamic content of antidiuretic activity was not changed significantly by deafferentation.

The results demonstrate that the amount of milk-ejection activity in the paraventricular nucleus is related to the number of neurosecretory granules and raises the intriguing question of why deafferentation of the hypothalamus influences its milk-ejection activity more than its antidiuretic activity.
EFFECT OF CYSTEINE ON THE BIOLOGICAL AND IMMUNOLOGICAL ACTIVITY OF HUMAN AND BOVINE PARATHYROID HORMONE
Authors: ZANELLI JOAN M. , ATKINS D. , PEACOCK M.
Published: December 2008

Human parathyroid hormone extracted from adenomata was assayed biologically by the release of calcium from mouse calvaria in organ culture and immunologically by immunoassay. The human hormone gave a logdose-response curve for calcium release and assayed at 12 units/mg in terms of the M.R.C. Bovine Research Standard A.

Reduction with hot cysteine hydrochloride increased the biological activity of human hormone threefold, and the bovine hormone 4½-fold. An increase in immunological activity could only be shown with bovine hormone, and the purer the preparation the less was the activation of both biological and immunological potencies.

Oxidation with hydrogen peroxide destroyed the biological activity of the bovine hormone but some residual immunological activity of the bovine and human hormones could always be detected. Back reduction with hot cysteine hydrochloride restored the biological and immunological activities of the bovine hormone and the immunological activity of the human hormone but never to the levels of the untreated hormones.

It is suggested that these changes in potency can be induced by changes in the chemistry of the molecule rather than in its metabolism and that the immunological differences between bovine and human hormone represent minor differences in the amino acid sequence of these two hormones.
ACCUMULATION OF NICOTINE IN PANCREATIC ISLETS AND CALCITONIN-PRODUCING CELLS IN MICE AND CHICKS DEMONSTRATED BY MICRO- AND WHOLE-BODY AUTORADIOGRAPHY
Authors: SLANINA PREMYSL , TJÄLVE HANS
Published: December 2008

By autoradiographic methods, nicotine was shown to be specifically accumulated in the pancreatic islets in mice. The results also indicated a high accumulation of nicotine in the parafollicular cells of the thyroid in mice and an accumulation was also shown in the ultimobranchial glands in chicks. Like the parafollicular cells of the thyroid in mammals, the ultimobranchial glands of birds are known to produce calcitonin. Metabolic studies with nicotine in vitro and autoradiographic studies with the main nicotine-metabolite cotinine, indicated an accumulation of unchanged nicotine (not metabolites) in the cells.

The results are discussed in view of the fact that biogenic amines have been shown to be operative in these endocrine organs. It is suggested that nicotine can share common transport and/or storage mechanisms with biogenic amines in the cells. An effect of nicotine on hormone storage and/or release may take place via an interference with aminergic mechanisms in the cells.
REFLEX RELEASE OF MILK-EJECTION ACTIVITY BY STIMULATION OF ORGANS IN THE PELVIC REGION IN SHEEP AS STUDIED BY CROSS-CIRCULATION EXPERIMENTS
Authors: PEETERS G. , HOUVENAGHEL A.
Published: December 2008

Cross-circulation experiments were performed on sheep by joining the jugular veins of two animals by anastomoses. One of the two animals (B) was a lactating ewe, and the release of hormones from the neurohypophysis in the other animal A (ewe, ram or wether) was investigated by recording the intramammary pressure in B.

The following types of stimulation were carried out on A: (1) distension of vagina or anus; (2) massage of seminal vesicles (SV) or cervix via the rectum; (3) deep massage of the rectal walls, SV or cervix excluded; (4) direct massage of cervix, SV or uterine horns through the abdomen; (5) manipulations in the deep pelvic cavity; (6) distension of the urinary bladder in rams and wethers and pressure upon the filled bladder.

Direct massage of cervix and uterine horns through the abdomen was ineffective. Stimulation of the urinary bladder by distension and pressure induced milk-ejection responses in some animals. Massage of the SV through the abdomen was hardly effective in rams but was effective in two out of seven wethers. The most efficient stimuli, classified according to their ability to induce milk ejection in B, were: distension of the vagina, stimulation of receptors in the retroperitoneal part of the rectum, manipulation in the deep pelvic cavity.

The hypothesis is advanced that reflex release of neurohormones is induced by stimulation of receptors of the afferent pelvic nerves wherever they are situated in the pelvic region. The release of neurohypophysial hormones, provoked by massage of the cervix or SV via the rectum in sheep, is to be attributed primarily to stimulation of receptors in the rectal wall. Reflex hormone release can be elicited just as well in wethers as in rams.
CORTICOSTEROID RELEASE BY ADRENAL TISSUE FROM FOETAL AND NEWBORN LAMBS IN RESPONSE TO CORTICOTROPHIN STIMULATION IN A PERIFUSION SYSTEM IN VITRO
Authors: MADILL DENISE , BASSETT J. M.
Published: December 2008

Adrenal glands from 24 foetal lambs (100–145 days gestation) and eight postnatal lambs (birth to 25 days of age) were used to study developmental changes in the responsiveness of the lamb adrenal to stimulation by synthetic adrenocorticotrophin (ACTH). A continuous flow incubation system in vitro (perifusion) was used in these studies. Addition of ACTH to the perifusion medium (0·3 μg Synacthen/ml) significantly increased the rate of corticosteroid release (as measured by a protein-binding assay) by adrenal tissue from foetuses of all ages studied. With tissue from foetuses of 137 days gestation or less, corticosteroid release during ACTH stimulation was < 2 μg/100 mg tissue in the 3 h following addition of ACTH to the perifusion medium. With tissue from foetuses older than this, the rate of corticosteroid release stimulated by ACTH increased as foetal age increased. At 145 days gestation (just before birth) release was 6·8 μg/100 mg tissue and in postnatal lambs less than 1 day old it was 12·3 μg/100 mg tissue during the 3 h following the start of stimulation. This increase in the response of the foetal adrenal to ACTH stimulation paralleled the increases in adrenal weight and plasma corticosteroid concentration which occurred before birth. With tissue from older lambs ACTH-stimulated corticosteroid release was 5·5 μg/100 mg tissue/3 h, a value comparable to that of 5·6 μg/100 mg tissue/3 h obtained with adrenal tissue from adult sheep.

Separation of corticosteroids in the perifusion medium by chromatography on LH 20 Sephadex indicated that adrenals from younger foetuses (< 137 days gestation) released approximately equal amounts of cortisol and corticosterone, whereas adrenals from older foetuses and postnatal lambs released mainly cortisol. Pituitary tissue from all foetuses stimulated corticosteroid release from adrenal tissue of adult sheep, implying that foetal pituitary stores of ACTH do not limit development of foetal adrenal cortex function during the last third of gestation. The results indicate that there is a marked increase during the last week of gestation in the responsiveness of the foetal adrenal to ACTH stimulation and that this increase is related to maturation of corticosteroid biosynthetic pathways during this period.
REGULATION OF GROWTH HORMONE SECRETION IN THE OVINE FOETUS
Authors: WALLACE A. L. C. , STACY B. D. , THORBURN G. D.
Published: December 2008

The rate of removal of immunoreactive, intravenously injected 125I-labelled sheep growth hormone (GH) was used to calculate metabolic clearance rates (MCR) in two foetal lambs at 130 days of gestation and in two 6-day-old lambs. The mean MCR calculated for the foetuses was 2·9 ml/min/kg and for the lambs 3·1 ml/min/kg. The concentration of GH in plasma sampled before injection was determined immunologically and the values were used to calculate production rates. A production rate of 924 ng GH/min was calculated for the foetuses and 85 ng GH/min for the lambs. The effect of sectioning the pituitary stalk was studied in two foetuses; after the operation there was a rapid decrease in the circulating levels of GH. Hypophysectomy in two other foetuses also caused an abrupt decrease in plasma GH concentration.

It was concluded from these experiments that the exceptionally high concentrations of GH in the plasma of foetal lambs could not be attributed to impaired removal of the hormone from the circulation. The direct cause of the increased hormone concentrations was a high rate of GH secretion resulting from active stimulation of the foetal pituitary by the hypothalamus.
THE EFFECT OF METABOLITES OF TESTOSTERONE ON THE VIABILITY OF HAMSTER EPIDIDYMAL SPERMATOZOA
Authors: LUBICZ-NAWROCKI C. M.
Published: December 2008

The effects of testosterone, dihydrotestosterone, 3α- and 3β-androstanediol on the fertilizing capacity of mature epididymal spermatozoa and on the production of fructose by the seminal vesicles were compared in golden hamsters. When injected subcutaneously into castrated animals, 100 μg testosterone, 75 μg dihydrotestosterone but only 12·5 μg 3α-androstanediol per day were required to maintain the fertilizing capacity at the control level for 12 days; 3β-androstanediol failed to maintain the fertilizing capacity of epididymal spermatozoa for 12 days.

Although testosterone and dihydrotestosterone were equipotent in stimulating production of fructose by the seminal vesicles, 3α- and 3β-androstanediol were much less effective. The discrepancy in the response of the cauda epididymidis and seminal vesicles to 3α-androstanediol suggests that the hormonal requirements for sperm survival in the cauda epididymidis differ from those for the production of fructose in seminal vesicles.

The results suggest that circulating testosterone may be relatively inactive in the cauda epididymidis and that the maintenance of fertilizing capacity of epididymal spermatozoa might be correlated with the reduction of dihydrotestosterone to the more potent androgen 3α-androstanediol by mature spermatozoa.
A SOLID-PHASE RADIOIMMUNOASSAY FOR OVINE FOLLICLE-STIMULATING HORMONE
Authors: CUNNINGHAM N. F. , HEBERT C. NANCY
Published: December 2008

A radioimmunoassay using antibody-coated polystyrene tubes is described, which is suitable for the estimation of follicle-stimulating hormone (FSH) levels in sheep blood plasma. Ovine FSH was labelled with 125I by an enzymic method employing lactoperoxidase and H2O2, and was stable for several months at −15 °C. Antisera to ovine FSH were raised in rabbits. Standard curves for unlabelled FSH obtained by this method with different preparations of labelled FSH showed reproducible slopes from day to day.

Ovine luteinizing hormone (LH) and thyroid-stimulating hormone (TSH) showed about 17% cross-reaction in the assay, necessitating the application of a correction to the FSH values for samples of plasma containing more than 15 ng of LH or TSH/ml.

The FSH content of plasma from wethers and anoestrous ewes ranged from 20 to 120 ng/ml.
A RADIOIMMUNOASSAY FOR β-MELANOCYTE-STIMULATING HORMONE IN HUMAN PLASMA
Authors: THODY A. J. , PLUMMER N. A.
Published: December 2008

A method is described for the radioimmunoassay of β-melanocyte-stimulating hormone (β-MSH) in human plasma. It was capable of detecting 20–30 pg β-MSH and was unaffected by the presence of α-MSH and human adrenocorticotrophic hormone. However, cross-reactivity did occur with β-glutamyl MSH (porcine).

A simple technique employing porous glass (Florisil) was used to extract β-MSH from plasma. In normal male subjects plasma β-MSH levels ranged from 21 to 133 pg/ml. In patients receiving cortisol therapy for Addison's disease slightly elevated levels were found. Much higher levels were found in patients who had undergone bilateral adrenalectomy as treatment for Cushing's disease.
THE EFFECT OF INTRAHYPOTHALAMIC INFUSIONS OF DOPAMINE AND NORADRENALINE ON OVULATION IN RESERPINE-TREATED FEMALE RATS
Authors: CRAVEN R. P. , McDONALD P. G.
Published: December 2008

Cyclic female rats were treated with reserpine (5 mg/kg) on the 2nd day of dioestrus (15.00 h) or on the day of pro-oestrus (11.30 h) to produce a total or partial depletion of brain amines. Ovulation was inhibited in 18 out of 21 rats. Intrahypothalamic infusions of 0·4–80 μg dopamine or noradrenaline on the afternoon of pro-oestrus did not restore ovulation in reserpine-treated rats. In normal pro-oestrous rats, 80 μg dopamine significantly inhibited ovulation, whereas 80 μg noradrenaline had no significant effect. Electrochemical stimulation of the basal hypothalamus or the administration of luteinizing hormone induced ovulation only in those animals treated with reserpine at pro-oestrus. The results indicate that reserpine exerts a marked peripheral effect when given on the 2nd day of dioestrus and has a partial effect on the ovaries when administered at pro-oestrus. The failure of monoamines to induce ovulation suggests that some aminergic synapses involved in gonadotrophin release may lie outside the medial basal hypothalamus. In addition, high levels of dopamine appear to exert an inhibitory action on the release of pituitary gonadotrophins.
THE UPTAKE OF TESTOSTERONE AND ZINC IN VITRO BY THE HUMAN BENIGN HYPERTROPHIC PROSTATE
Authors: REED M. JOAN , STITCH S. R.
Published: December 2008

The uptake of 65Zn and [1,2-3H]testosterone by minced tissue of human benign hypertrophic prostates and the subcellular distribution of radioactivity were examined. The nature of steroid and 65Zn binding by the cytosol (105000 g supernatant) fraction was investigated by gel filtration, ion-exchange chromatography and electrophoresis.

It was found that steroid binding after incubation at 4°C was specific. One or two regions of steroid binding were observed after gel filtration of the cytosol using Sephadex G-200, depending upon incubation conditions. Binding of 65Zn was found in the low molecular weight peak after G-200 gel filtration. Equimolar CdCl2 and 65ZnCl2 were incubated with [1,2-3H]testosterone and minced tissue and the cytosol was subjected to gel filtration. Compared with control values, without CdCl2, reduction of 65Zn binding by about 50% occurred, while binding of 3H-labelled steroid was unaffected. Electrophoresis and ion-exchange chromatography showed that 65Zn and 3H-labelled steroid were bound to different proteins. A sample of the zinc-binding protein was prepared by ion-exchange chromatography and the homogeneity was checked by electrophoresis.
ROLE OF THE KIDNEY IN THE METABOLISM OF LUTEINIZING HORMONE
Authors: de KRETSER D. M. , ATKINS R. C. , PAULSEN C. A.
Published: December 2008

Autoradiographic localization of 125I-labelled luteinizing hormone (LH) in the renal proximal convoluted tubule of rats initiated a study of the role of the kidney in the metabolism of LH. Incubation of 131I-labelled LH with rat renal homogenates for 90 min failed to destroy its immunological reactivity.

The plasma half-life of 131I-labelled LH injected i.v. was investigated in normal ewes and rams. Preliminary studies indicated that the use of a preparation containing a high proportion of 'damaged' iodinated hormone could erroneously prolong the plasma half-life. Before use, 131I-labelled LH was purified by gel filtration and column chromatography using DEAE-cellulose. The mean plasma half-life of 131I-labelled LH in normal ewes was 26·7 min and was not significantly altered after oophorectomy (31·1 min). After bilateral oophorectomy and nephrectomy, marked prolongation of the plasma half-life was observed (mean 70·7 min). In normal rams, mean plasma half-life of 131I-labelled LH was 32·0 min, after orchidectomy 44·0 min and after orchidectomy and nephrectomy 82·0 min. The plasma half-life of 131I-labelled LH in a nephrectomized ewe maintained on haemodialysis was also prolonged (67·5 min), the determination being performed 24 h after the last haemodialysis. Although the kidney does not degrade LH, the plasma half-life was significantly increased after nephrectomy. This suggests that the localization of 125I-labelled LH in the proximal convoluted tubule may represent a secretory mechanism allowing renal excretion of LH.
THE METABOLIC CLEARANCE RATE, PRODUCTION RATE AND CONVERSION RATIOS OF OESTRONE IN THE SHEEP
Authors: CHALLIS J. R. G. , HARRISON F. A. , HEAP R. B.
Published: December 2008

The metabolic clearance rate of oestrone from whole blood and its conversion to oestradiol-17β and oestradiol-17α were measured in pregnant and non-pregnant sheep using tracer kinetic techniques. The clearance rate of oestrone for all animals (3·435 ± 0·212 (s.e.m.) 1/min) was significantly greater than that of oestradiol-17β (2·449 ± 0·155 1/min). The mean conversion ratio of oestrone to oestradiol-17β was 23·8±1·6%, and that of oestrone to oestradiol-17α was 17·7 ± 2·5%. The transfer constant of oestrone to oestradiol-17β was estimated to be 17·5 ± 1·6% compared with that of oestradiol-17β to oestrone which was 23·2 ± 2·5%. The production of oestrone increased from values of 0·141 and 0·240 μg/min up to 2 days before parturition, to between 0·660 and 1·881 μg/min during the last 24 h of pregnancy; these values were appreciably greater than those of oestradiol-17β.

During the continuous infusion of [3H]oestrone or [3H]oestradiol-17β and when a steady state had been reached, the uptake by erythrocytes of [3H]oestrone was 22·3%, that of [3H]oestradiol-17β, 6·6%, and that of [3H]oestradiol-17α, 22·0%. In three experiments on one sheep, the uptake of [3H]oestrone across the head was 11–16%.
STEROID METABOLISM BY ADULT RAT ADRENOCORTICAL CELLS IN MONOLAYER CULTURE
Authors: O'HARE M. J. , NEVILLE A. MUNRO
Published: December 2008

The patterns of exogenous steroid metabolism by rat adrenocortical zona fasciculata and zona reticularis cells cultured together as a monolayer have been examined. In the continued presence of corticotrophin (ACTH), the cultured cells synthesized corticosterone, 18-hydroxydeoxycorticosterone and deoxycorticosterone from [3H]pregnenolone. In the prolonged absence of ACTH, however, [3H]pregnenolone was metabolized mainly to progesterone, 20α-dihydroprogesterone, 20α-hydroxy-5α-pregnan-3-one and 5α-pregnane-3β,20α-diol with small amounts of 5α-pregnane-3,20-dione, 11β-hydroxyprogesterone and 11β-hydroxy-20α-dihydroprogesterone, while virtually no corticosterone, 18-hydroxydeoxycorticosterone or deoxycorticosterone were produced. While 5-ene-3β-hydroxysteroid dehydrogenase-isomerase activity persisted at a substantial level in unstimulated cells and the 11β- and 18-hydroxylases were reduced but still present, 21-hydroxylase activity was almost completely lost when ACTH was omitted from the culture medium. These changes in enzyme activities were completely reversed by the addition of ACTH, cyclic AMP or dibutyryl cyclic AMP to unstimulated cultures for 4–5 days, during which time no proliferation of adrenal cells was observed.
METABOLISM OF [4-14C]17α-HYDROXYPROGESTERONE TO UNCONJUGATED METABOLITES IN THE HUMAN FOETO-PLACENTAL UNIT AT MID-PREGNANCY
Authors: LING W. , COUTTS J. R. T. , MACNAUGHTON M. C. , SOLOMON S.
Published: December 2008

Labelled 17α-hydroxyprogesterone was injected into the umbilical vein of each of two male previable human foetuses at the time of laparotomy. The umbilical circulation remained intact for 3 min after which time the tissues of the foetuses, placentae and cords were removed, extracted and the labelled unconjugated metabolites formed were identified. The mid-pregnancy human foetus has a high capacity for metabolizing 17α-hydroxyprogesterone, forming corticosteroids, C-19 steroids and a variety of reduced and hydroxylated metabolites. Androstenedione and testosterone were isolated from both the foetal adrenals and testes but the older of the two foetuses studied contributed in major part to this synthesis. All the foetal tissues examined showed a remarkable capacity to metabolize 17α-hydroxyprogesterone.
FORMATION OF CONJUGATED METABOLITES AFTER INJECTION OF [4-14C]17α-HYDROXYPROGESTERONE INTO THE UMBILICAL VEIN OF THE HUMAN FOETUS AT MID-PREGNANCY
Authors: LING W. , COUTTS J. R. T. , MACNAUGHTON M. C. , SOLOMON S.
Published: December 2008

After injection of [4-14C]17α-hydroxyprogesterone into the umbilical vein of two male human foetuses at mid-pregnancy a number of steroid conjugates were isolated from the foetal adrenals, liver, intestines and residual tissues, confirming the capacity of the human foetus to conjugate an extensive range of steroid substrates. The conjugated steroids isolated were 17α-hydroxypregnanolone sulphate (liver, intestine), 3β,17α-dihydroxy-5α-pregnan-20-one sulphate (residue), pregnanetriol sulphate (liver, residue), cortisol sulphate (adrenal), pregnanetriol glucosiduronate (liver, residue) and 17α-hydroxypregnanolone glucosiduronate (liver).
MECHANISM OF OESTRADIOL ACTION ON THE RAT UTERUS: INDEPENDENCE OF CYCLIC AMP, PROSTAGLANDIN E2 AND β-ADRENERGIC MEDIATION
Authors: ZOR U. , KOCH Y. , LAMPRECHT S. A. , AUSHER J. , LINDNER H. R.
Published: December 2008

The hypothesis that cyclic AMP plays an essential role in mediating the biological action of oestradiol on the uterus, was tested by determining the tissue concentration of the cyclic nucleotide after incubation of uteri of immature rats with oestradiol or after injection of this steroid into immature or ovariectomized rats. The effect of known stimulants of uterine adenyl cyclase, namely β-adrenergic drugs and prostaglandin E2 (PGE2), on the level of cyclic AMP in the uterus was also examined both in vitro and in vivo.

In either system, oestradiol failed to enhance the concentration of cyclic AMP in the uterine tissue, whereas adrenaline or the almost purely β-adrenergic agonist isoprenaline (isoproterenol) caused cyclic AMP accumulation that was susceptible to inhibition by the β-adrenergic blocking agent propranolol. Prostaglandin E2, and to a much lesser degree prostaglandin F2α, increased cyclic AMP concentration in the uterus, but the effect of PGE2 was not inhibited by propranolol. It may be concluded that oestradiol does not cause appreciable stimulation of PGE2 synthesis or activation of β-adrenergic receptors in the rat uterus since, otherwise, increased cyclic AMP production should have been observed after the treatment with oestradiol.

Isoprenaline mimicked the stimulatory action of oestradiol on uterine ornithine decarboxylase. However, this action of isoprenaline was abolished by propranolol, whereas that of oestradiol was only slightly, though significantly, inhibited.

The present findings do not support the view that the action of oestradiol on the uterus is mediated by cyclic AMP, and also suggest that β-adrenergic receptors and PGE2 can have only a minor role, if any, in the mechanism of action of this hormone.
EFFECT OF HYPOPHYSECTOMY ON THE GROWTH HORMONE RESPONSE TO INSULIN-INDUCED HYPOGLYCAEMIA
Authors: ROBERTS M. MAUREEN , FORREST A. P. M. , RICHARDS S. , STEWART H. J. , BOYNS A. R.
Published: December 2008

Plasma growth hormone (GH) levels were measured in 55 patients with advanced breast cancer, before and 3 months after pituitary ablation either by yttrium-90 implantation or by transethmoidal hypophysectomy. It was found that four of the 46 patients tested before ablation had an 'absent' GH response to insulin-induced hypoglycaemia. A comparison of the GH response to insulin-induced hypoglycaemia after yttrium implantation and transethmoidal hypophysectomy revealed no difference between the two procedures in the degree of pituitary ablation achieved. A partial GH deficiency occurred in 30% of patients after yttrium implantation but in only 4% after transethmoidal hypophysectomy.
THE ISOLATION AND BIOCHEMICAL CHARACTERIZATION OF THREE NEUROPHYSINS OF THE SHEEP
Authors: WATKINS W. B.
Published: December 2008

Three neurophysins have been isolated from acetone-dried sheep posterior lobe powder and have been named neurophysins I, II and III. Neurophysins I, II and III account for approximately 15, 15 and 70%, respectively of the total neurohypophysial hormone-binding proteins present in the sheep posterior pituitary lobe. All the neurophysins bind oxytocin and [8-arginine]-vasopressin. Neurophysins I and II each were found to contain one molecule of histidine/molecule of protein but to lack methionine, whereas neurophysin III contained no histidine but had one molecule of methionine/molecule of protein. The molecular weights of sheep neurophysins I, II and III were 11348, 9803 and 10377, respectively, as determined by amino acid analysis. An approximate value of 10000 was estimated for the apparent molecular weight of the neurophysins by gel exclusion chromatography on Sephadex G-75. Solid amorphous complexes were formed between the neurophysins and oxytocin as well as with [8-arginine]-vasopressin. In each case one molecule of neurophysin complexed with one molecule of hormone. The stoichiometry of the sheep neurophysins relative to the neurohypophysial hormones is discussed.
THE DESIGNATION OF THE MAJOR GUINEA-PIG NEURAL LOBE PROTEIN AS A NEUROPHYSIN
Authors: WATKINS W. B. , ELLIS H. K.
Published: December 2008

[35S]Cysteine was injected intracisternally into guinea-pigs and 5 h later the soluble proteins of the neural lobe were subjected to electrophoresis on starch and polyacrylamide. In both systems approximately 80% of the total radioactivity was recovered in a single peak with an electrophoretic mobility corresponding to the position of the major protein component. The proteins present in the guinea-pig neural lobe were extracted in 0·1 m-HCl. Fractionation of the protein—neurohypophysial hormone complex on Sephadex G-75 resulted in the isolation of a protein which cross-reacted immunologically with an antiserum raised against porcine neurophysin II. The protein designated a neurophysin contained one molecule of lysine, isoleucine and tyrosine per molecule of protein. It contained no histidine or methionine and its minimum molecular weight was estimated as 8436 by amino acid analysis.
EFFECT OF CORTISOL TREATMENT ON FREE AMINO ACID LEVELS IN RATS
Authors: DE LOECKER W. , STAS M. L.
Published: December 2008

Changes in the concentrations of free amino acids in intracellular fluids and blood plasma were measured in rats treated with cortisol. Increasing age raised the concentrations of free amino acids in plasma, while in liver, with the exception of glycine and alanine, decreased concentrations were observed. Cortisol treatment reduced free amino acid levels in plasma and liver which suggested a progressive catabolism of body proteins and increased protein synthesis in the liver. In skeletal muscle of control rats the free amino acid concentrations increased during the experimental period. Cortisol increased the concentration of certain amino acids and decreased that of others due to an increased protein turnover in muscle.
THE EFFECTS OF AGE AND OESTRONE TREATMENT ON DNA POLYMERASE ACTIVITY IN ANTERIOR PITUITARY GLANDS OF MALE RATS
Authors: MASTRO ANDREA , HYMER W. C.
Published: December 2008

DNA polymerase activity was found in the cytoplasmic fraction and in isolated nuclei from anterior pituitary glands of male rats. The enzyme activity was assayed by measuring the incorporation of [3H]dTTP into DNA in a medium containing Tris-HCl buffer (pH 8·5), the four deoxyribonucleoside triphosphates, Mg2 +, ATP and activated calf thymus DNA. The DNA polymerase activity decreased with age in glands from animals aged 25 days to over a year but increased after oestrone treatment in vivo. These changes in activity, more pronounced in the cytoplasmic fraction than in the isolated nuclei, were similar to changes in DNA synthesis measured in anterior pituitary glands under the same physiological conditions.

Isolated nuclei also retained endogenous DNA synthetic activity in the absence of added template. Addition of a cytoplasmic fraction to the reaction medium stimulated activity by as much as 1·9-fold but the degree of stimulation was the same whether the cytoplasm was from young, old or oestrone-treated animals.
THE INFLUENCE OF PHOTOPERIOD ON NEST BUILDING, OVARIAN DEVELOPMENT AND LUTEINIZING HORMONE SECRETION IN CANARIES (SERINUS CANARIUS)
Authors: FOLLETT B. K. , HINDE R. A. , STEEL ELIZABETH , NICHOLLS T. J.
Published: December 2008

Female canaries were exposed to various lighting schedules in January—February to assess the photoperiod necessary for reproductive development. Nest building was not increased with lighting schedules of 8 h light: 16 h darkness per day (8L: 16D) and 10L: 14D but was increased after 4 weeks of 12L: 12D or 14L: 10D. Placing of nest material was greatest with a lighting schedule of 14L: 10D. Plasma and pituitary luteinizing hormone (LH) levels were low when 8L: 16D was used and the ovaries and oviducts remained undeveloped. There was a significant rise in the weights of the ovaries and oviducts with 10L: 14D per day. This change was not reflected in the plasma LH level but the amount of LH in the pituitary was increased. Exposure to 12L: 12D or 14L: 10D caused substantial development of ovaries and oviduct growth, and significantly increased levels of plasma and pituitary LH. These two groups were indistinguishable in all these parameters.

Oestrogen treatment of a group exposed to 8L: 16D decreased plasma and pituitary LH in four out of six birds. Behaviourally, some of these birds showed an increase in gathering and placing of nest material. In an oestrogen-treated group exposed to 14L: 10D no effect was seen on plasma LH concentration, but the group showed significantly more gathering and placing behaviour than untreated birds. Oviduct weight was increased in both oestrogen-treated groups.
CHANGES IN THE COMPOSITION AND YIELD OF THE MAMMARY SECRETION OF COWS DURING THE INITIATION OF LACTATION
Authors: HARTMANN P. E.
Published: December 2008

Mammary secretion (1·2–2·0 ml) was collected from the milk sinus of each mammary gland (quarter) of two pregnant heifers and eight pregnant cows (dry period 49–229 days), first at weekly intervals from 40 days before parturition, then with increasing frequency as parturition approached. The progressive changes in the concentration of lactose, glucose, casein, non-casein protein and fat in the mammary secretion were determined. Calves were separated from the cows immediately after birth and the yield and composition of milk from individual quarters were determined for 5 days after parturition. Two quarters (milked quarters) of each of a further five cows were milked throughout pregnancy, while the other two quarters (unmilked quarters) of each cow were allowed to involute (dry off) 63– 104 days before parturition. Small samples (5–10 ml) of secretion were collected from the unmilked quarters, first at weekly intervals after drying off and then every second day from 10 to 15 days before parturition. On the days that the unmilked quarters were sampled, corresponding composite milk samples were collected from the milked quarters and the progressive changes in the yield of milk, lactose and fat were determined. The changes in the concentration of lactose and glucose in the mammary secretion, during drying off in late lactation, were determined in an additional five cows.

In most cows allowed a usual dry period, and in the unmilked quarters of cows in which two quarters were milked throughout pregnancy, the concentration of lactose gradually increased from about 8 to 12 days before parturition to reach levels of about half those found in normal milk just before parturition. However, in some cows the concentration of lactose was low until 1–2 days before parturition and then increased abruptly, whereas in others the concentration of lactose increased slowly from as early as 32 days before parturition. A further rapid increase in the concentration of lactose in the mammary secretion occurred between 0 and 4 days before parturition in all cows. This latter increase was accompanied by an abrupt increase in the yield of milk, lactose and fat in the milked quarters of the cows in which two quarters were milked throughout pregnancy. These observations suggest that the initiation of lactation in the cow develops in two phases, a limited secretion of milk constituents occurs in late pregnancy and then 0–4 days before parturition copious secretion (lactogenesis) occurs.
STIMULATION OF GROWTH HORMONE RELEASE FROM SUPERFUSED RAT PITUITARY BY EXTRACTS OF HYPOTHALAMUS AND OF HUMAN LUNG TUMOURS
Authors: BECK CHRISTINE , LARKINS R. G. , MARTIN T. J. , BURGER H. G.
Published: December 2008

The paradoxical plasma growth hormone (GH) responses to oral glucose in certain patients with lung cancer prompted an examination of tumour extracts for GH releasing activity. Exposure of superfused rat pituitary to pulses (30 s) of aminophylline and to extracts from rat, sheep and human hypothalami resulted in a rapid and short-lived release of immunoreactive rat GH into the medium. Fresh extracts from five lung tumours, and from the surrounding lung tissue of four of these tumours significantly stimulated the release of GH, while extracts of a metastatic chondrosarcoma and normal rat lung were inactive. Gel filtration experiments suggested that the releasing activity in rat, sheep and human hypothalamic tissue and in human lung tumour extracts was present in at least two molecular species of different sizes.
THE METABOLISM OF TESTOSTERONE BY HUMAN SKIN IN DISORDERS OF HAIR GROWTH
Authors: JENKINS J. S. , ASH S.
Published: December 2008

The metabolism of testosterone by skin from patients with disorders of hair growth in the presence of normal testosterone levels has been studied in vitro and compared with the metabolic activity of normal skin. The main metabolites formed were dihydrotestosterone, androstenedione, androsterone and androstanedione. In four out of six females with hirsutism, the skin produced increased amounts of dihydrotestosterone and also androstenedione. A patient with the rare condition of unilateral hirsutism showed no difference in metabolic activity between the hirsute and non-hirsute sides. In localized failure of androgenically determined hair growth, seen in three beardless males, the metabolism of the hairless area was greater than that of the normally hairy abdomen. Four patients with testicular feminization and complete absence of body hair were studied and the formation of dihydrotestosterone ranged from low to high normal levels.
INTERSTRAIN DIFFERENCES IN NUMBER, SIZE AND MORPHOLOGY OF VESICULAR GLAND CELL NUCLEOLI IN INTACT, CASTRATED AND TESTOSTERONE-TREATED MICE
Authors: IVÁNYI DAGMAR
Published: December 2008

The nucleoli of vesicular gland cells from intact, castrated and testosterone-treated mice of strains A and C57Bl/10 were studied in smears specifically stained for the demonstration of RNA-containing structures using the light microscope. The size, number and morphology of vesicular gland cell nucleoli were found to be influenced by testosterone. After castration the size of the nucleoli and the percentage of nucleoli actively engaged in RNA synthesis decreased and the nucleolar coefficient (NC) increased. After testosterone treatment of intact as well as castrated animals the size of the nucleoli and the percentage of active nucleoli increased and the NC diminished. Interstrain differences were calculated for all values obtained. In C57Bl/10 animals the NC was always higher and the size of nucleoli, as well as the percentage of active nucleoli, were always lower than in strain A mice.
PROGESTERONE CONCENTRATIONS IN THE PERIPHERAL PLASMA OF THE BLUE FOX (ALOPEX LAGOPUS) DURING PREGNANCY AND THE OESTROUS CYCLE
Authors: MØLLER O. M.
Published: December 2008

A competitive protein-binding assay was evaluated and employed in the measurement of progesterone in serial plasma samples obtained from pregnant, non-pregnant and non-receptive blue-fox vixens.

At the beginning of the period of pro-oestrous vulval swelling, the plasma progesterone concentration was always found to be below 2 ng/ml. Towards the end of pro-oestrus and during the period of oestrus (sexual receptivity) the concentration increased rather quickly. On the 3rd and the 4th days of oestrus, i.e. when most of the vixens were mated, the plasma progesterone concentrations were about 30 ng/ml (range: 18–36 ng/ml). During gestation (53 or 54 days) the plasma progesterone level rose very steeply and attained a maximum plateau (> 80 ng/ml) between days 5 and 8 post coitum, remained high until about day 20, but thereafter fell rather quickly to below 30 ng/ml between days 35 and 40. Later on the progesterone level fell gradually to below 5 ng/ml at the day of parturition, and, 4 days post partum and later, the levels were below the limit of the sensitivity of the assay used (< 2 ng/ml).

The progesterone values and profiles obtained from the non-pregnant vixens (mated vixens which failed to whelp) corresponded clearly to those obtained in the pregnant vixens. Indeed, even in two non-receptive vixens (unwilling to mate during the mating season) typical progesterone profiles were obtained during a period of about 70 days.
THE ROLE OF ELECTROLYTES OF THE ENDOMETRIUM AND UTERINE FLUID DURING DELAYED IMPLANTATION IN RATS
Authors: SETTY B. S. , SINGH MAN MOHAN , CHOWDHURY S. R. , KAR AMIYA B.
Published: December 2008

Sodium and potassium levels were determined in the rat endometrium and uterine washings during normal and 'delayed' implantation. Both endometrium and uterine washings of normal rats differed from those of 'delayed' animals in their electrolyte concentrations. A dose of oestradiol dipropionate (1 μg/rat) capable of inducing implantation in 'delayed' rats (ovariectomized and maintained on progesterone) did not evoke any significant changes in electrolyte concentration of either the endometrium or uterine washings. These findings are discussed in the light of a hypothesis regarding delayed implantation in rats.
ENDOGENOUS STEROID SULPHATES AND GLUCURONIDES IN THE GALLBLADDER BILE FROM EARLY AND MID-TERM HUMAN FOETUSES
Authors: HUHTANIEMI I.
Published: December 2008

The neutral steroids derived from their conjugates present in a pool of bile from 20 human foetuses were analysed by gas—liquid chromatography and gas chromatography— mass spectrometry. Ten monosulphates, twelve disulphates and seven glucuronides were detected, but no free steroids were found. Both saturated and unsaturated steroids of the C19- and C21-series were detected. The glucuronides of 5β-pregnane-3α,20α-diol, 5α-pregnane-3β,16α,20α-triol and 3α-hydroxy-5β-pregnan-20-one as well as the monosulphate of 16α-hydroxydehydroepiandrosterone were present in the highest concentrations. Other major components were the monosulphates of dehydroepiandrosterone, pregnenolone and 16α-hydroxypregnenolone and the disulphates of 5-androstene-3β,17α-diol, 3β, 17β-dihydroxy-5-androsten-16-one and 5β-prenane-3ξ,20α,21-triol. The total concentration of the monosulphate conjugates was 435 μg/100 g sample (wet weight), of the disulphates 363 μg/100 g and of the glucuronides 815 μg/100 g.

Many of the compounds detected have previously been found in the foetal liver and intestinal contents. It is therefore concluded that during early and mid-gestation the foetal liver is already excreting many steroid conjugates through the biliary tract into the intestinal canal. As in other foetal compartments, considerable amounts of steroid sulphates were detected. However, the presence of steroid glucuronides in the bile suggests that the formation of hepatic glucuronides already occurs during the foetal period.
ABNORMAL INSULIN SECRETION IN PARKINSON'S DISEASE BEFORE AND DURING l-DIHYDROXYPHENYLALANINE (l-DOPA) THERAPY
Authors: VAN WOERT M. H. , MUELLER P. S. , AMBANI L. M. , RATHEY U.
Published: December 2008

Insulin and glucose metabolism were studied in parkinsonian patients before and during treatment with l-DOPA and in a chronically ill, elderly, control group of patients. The parkinsonian patients had a low absolute glucose disappearance rate and a low serum insulin response to intravenous glucose compared with controls, which was not altered by l-DOPA therapy. The serum glucose and insulin responses to the oral glucose tolerance tests in parkinsonian patients were similar to those of the control group. Normal immediate insulin responses were observed after infusions of tolbutamide and glucagon.

l-DOPA decreased serum insulin and glucose levels during the first 90 min of the oral glucose tolerance test and produced an increase in concentration of human growth hormone in serum of some parkinsonian patients. l-DOPA therapy had no effect on intravenous tolbutamide and glucagon tolerance tests. Our results indicate a selective defect in the mechanism of intravenous glucose-induced insulin release in patients with Parkinson's disease.