bluuebunny/crossref_metadata_2025 huggingface dataset:
THYROCALCITONIN AND ITS ROLE IN CALCIUM HOMEOSTASIS
Authors: CARE A. D. , DUNCAN T. , WEBSTER D.
Published: December 2008

In pigs, the control of hypercalcaemia was significantly impaired by thyroidectomy.

Hypercalcaemic perfusion of the pig thyroid (which contains no parathyroids) in situ produced a systemic hypocalcaemic response which reached its maximum after about 2 hr. perfusion and which persisted for as long as the hypercalcaemic stimulus was applied. Thyroid venous plasma from a gland so perfused, when cross-transfused into a second pig, caused a hypocalcaemic reaction similar to that produced by the intravenous injection of porcine thyrocalcitonin preparations.

Hypermagnesaemia did not appear to influence the release of thyrocalcitonin.

A hypocalcaemic response to hypercalcaemic perfusion of the thyroid, similar to that seen in intact pigs, occurred in parathyroidectomized pigs, provided that the initial plasma calcium level was maintained by suitable calcium supplement to the diet.

Hypocalcaemic perfusion of the thyroid, in either intact or parathyroidectomized pigs, resulted in a rise in the systemic plasma calcium concentration, although this rise was only consistently observed when the systemic plasma calcium level was already low as a result of thyrocalcitonin secretion.

It is suggested that the secretion of thyrocalcitonin is controlled by a negative feedback mechanism operating through the plasma calcium concentration, and that because of the rapidity of its release, action and elimination, relative to parathyroid hormone, thyrocalcitonin acts as a fine regulator of calcium homeostasis.
OXIDATIVE PHOSPHORYLATION AND HEPATIC CHANGES IN RELATION TO PROLONGED ALDOSTERONE ADMINISTRATION
Authors: BEDRAK E. , SAMOILOFF V. , GOLDBERG G. M.
Published: December 2008

Prolonged aldosterone administration to mice was investigated in relation to liver function. Daily injections of 2 μg. d-aldosterone monoacetate/g. body weight for 60 days adversely affected oxidative phosphorylation of liver mitochondria. The value for the P:O ratio of controls, 3·21, dropped to 2·01, 2·86, 2·45 and 2·79 for mice treated with aldosterone for 20, 30, 50 and 60 days, respectively. The impaired oxidative phosphorylation was neither accompanied by an increase in adenosine triphosphatase activity of liver mitochondria nor by a change in plasma transaminases. Corresponding morphological changes were observed in liver parenchyma starting with hydropic degenerations in early lesions, and single cell necrosis accompanied by mitotic activity (regeneration) in advanced lesions. It seems therefore that hyperaldosteronism might be noxious to liver parenchyma and hepatic function.
THE INDUCTION OF WITHDRAWAL BLEEDING WITH QUINESTRADOL (PENTOVIS) IN SPAYED MONKEYS, AND SOME OBSERVATIONS ON ITS EXCRETION AND THAT OF OESTRIOL IN THE URINE
Authors: ECKSTEIN P. , GREIG MARION , BUTT W. R.
Published: December 2008

1. Daily oral administration of between 0·1 and 0·5 mg. quinestradol (3-cyclopentyl ether of oestriol) for 14 days to four spayed monkeys induced macroscopic uterine haemorrhage in three and microscopic bleeding in the fourth. This is in marked contrast to the finding that in women this compound seems to act only on the lower genital tract and does not cause uterine withdrawal bleeding.

Oestriol, given in the same way at a daily dosage of 0·82 mg., also induced withdrawal bleeding in one monkey.

2. The urinary excretion of quinestradol and oestriol was studied in two of the monkeys and that of quinestradol alone in a post-menopausal woman. The findings indicate that some quinestradol is excreted as oestriol, which in monkeys, unlike women, appears to be unconjugated.

3. Possible reasons for the observed differences in the biological effects of quinestradol in the two species are briefly discussed.
BLASTOCYST IMPLANTATION DURING POST-PARTUM PSEUDOPREGNANCY IN THE RAT
Authors: MANTALENAKIS S. J. , KETCHEL M. M.
Published: December 2008

Five-day blastocysts were transferred to the uteri of rats during post-partum pseudopregnancy. Low implantation rates were observed when blastocysts were transferred on days 5 to 11 of lactation pseudopregnancy to recipients which were suckling their litters. Two incidents of asynchronous implantation occurred. If the suckling young were removed at the time of blastocyst transfer, high rates of implantation were obtained. If the cervix of the recipients was electrically stimulated at the time of the post-partum oestrus, implantation, while delayed, occurred at a high rate even though the recipients were suckling their litters. These results suggest that the cervical stimulation which occurs at copulation is a requirement for implantation in normally mated lactating rats.
UTERINE CHANGES AFTER INTRALUMINAL ADMINISTRATION OF HISTAMINE AND OESTROGEN
Authors: CECIL HELENE C. , BITMAN J. , HANNUM J. A. , TREZISE LOIS
Published: December 2008

Uterine vascular permeability changes, measured quantitatively by trypan blue accumulation, and measurements of uterine water content, were used to study the postulated role of histamine as a mediator of oestrogen action. Histamine (H), oestradiol (E), 1·3% NaCl solution, an antihistamine (AH—diphenhydramine hydrochloride—Benadryl) or xylene (X), was injected intraluminally into each uterine horn of ovariectomized rats. At intervals of 1/4–24 hr. after treatment uterine vascular changes were determined by comparing the trypan blue concentration of treated uteri with the concentration in ovariectomized controls. In the 1/4–1 hr. time periods 1·0 mg. H and 0·5–2·5 mg. AH showed increases 2 to 6 times greater than the slight permeability change induced by 0·04 μg. E or 1·3% NaCl, and were similar to that evoked by the inflammatory tissue irritant xylene. The characteristic uterine permeability effect of oestrogen was evident at 4 hr. at which time H and AH produced similar responses. However, histological examination showed a complete loss of epithelium of the uterine lumen caused by 1·0 mg. H, 0·5–2·5 mg. AH, and X during the first 4 hr. but only a partial loss with NaCl or E. When lower doses of histamine were administered, epithelial loss was reduced, and with 0·1 mg. histamine epithelial loss, uterine permeability, and water content approached those of rats treated with the 1·3% NaCl solution.
BIOCHEMISTRY OF HISTOLOGICALLY DEFINED ZONES IN THE ADRENAL CORTEX: CORTISOL SYNTHESIS IN THE HORSE
Authors: CAMERON E. H. D. , GRANT J. K.
Published: December 2008

The ability of cells from the zona fasciculata and zona reticularis of the horse adrenal cortex to transform [7α-3H]pregnenolone, [4-14C]progesterone, [7α-3H]17α-hydroxypregnenolone and [4-14C]17α-hydroxyprogesterone to cortisol in vitro was investigated.

It was found that: (1) Both types of cell form cortisol from these steroids. (2) The transformation is greater in fascicular cells. (3) The formation of 17α-hydroxyprogesterone from pregnenolone (via either progesterone or 17α-hydroxypregnenolone) is slower that the subsequent formation of cortisol from 17α-hydroxyprogesterone. (4) The formation of 17α-hydroxyprogesterone from 17α-hydroxypregnenolone is rate-limiting in cortisol formation, but is about 2·4 times faster in fascicular than in reticular cells. (5) 17α-Hydroxylation of progesterone is also faster in fascicular than in reticular cells.
THE ACUTE PANCREATIC EFFECT OF ALLOXAN IN THE RABBIT
Authors: HOWELL S. L. , TAYLOR K. W.
Published: December 2008

The origin of the pronounced hypoglycaemic phase during the onset of alloxan diabetes in the rabbit has been investigated.

Blood sugar and serum insulin levels were recorded 6, 12 and 24 hr. after alloxan administration and were related to changes in the insulin content of the pancreas and to the rate of insulin release from pancreas slices in vitro at similar time intervals. During the phase of hypoglycaemia, serum insulin levels were elevated, and insulin release from the pancreas slices was markedly increased, but a decrease in the quantity of insulin extractable from the pancreas occurred during the same 6 hr. period.

These results indicate that the hypoglycaemia may result from an unregulated release of preformed insulin from the β cells, during their destruction after the administration of alloxan.
GAS CHROMATOGRAPHIC IDENTIFICATION OF THE URINARY OXOPREGNANE DERIVATIVES IN THE PREGNANT RABBIT
Authors: ALLEN J. G. , THOMAS G. H. , WRIGHT A. A.
Published: December 2008

The oxosteroid metabolites of the pregnant rabbit were identified by gas chromatography using a combination of chromatographic runs involving examination of the free and acetylated material on QF-1, the alcohols on SE-30 and the trimethylsilyl ethers on neopentyl glycol adipate (NGA). The oxidized material was run on QF-1 and NGA. The ketonic fraction consisted mainly of pregnanes, some of which were 20-oxosteroids (3α-hydroxy-5β-pregnan-20-one, 3α,6α-dihydroxy-5α-pregnan-20-one and its 5β-epimer, and 3α-hydroxy-5β-pregnane-11,20-dione), and two of which were 20α-ol-3-ones (20α-hydroxypregn-4-en-3-one and 20α-hydroxy-5β-pregnan-3-one). The detection of the latter two compounds directs attention to the catabolic pathway for pregnanediol which involves initially reduction of the 20-ketone.
SERUM AND URINE INSULIN IN LATE PREGNANCY AND IN A FEW PREGNANT LATENT DIABETICS
Authors: TRAYNER IRIS M. , WELBORN T. A. , RUBENSTEIN A. H. , FRASER T. RUSSELL
Published: December 2008

As measured both by immunoassay and bioassay during a glucose tolerance test (50 g.) on ten subjects in the third trimester of pregnancy, the serum insulin levels fasting, 1 and 2 hr. after glucose were raised at least threefold compared with the levels in 23 non-pregnant women.

The renal clearance of immunoassayable insulin was lower than that in the non-pregnant state (the mean in the pregnant subjects was 0·18 ml./min. compared with 0·45 ml./min. in the normal non-pregnant subjects).

In the same subjects the mean serum non-suppressible insulin-like activity, which is unaltered by oral glucose, was 1·5 times higher than the non-pregnant mean level, but this difference was not significant.

Four pregnant latent diabetics, tested similarly in the latter part of pregnancy, showed even higher fasting serum insulin levels than the normal pregnant subjects, but a lessened response to the same glucose load.
HORMONAL REQUIREMENTS FOR THE SURVIVAL OF BLASTOCYSTS IN THE UTERUS OF THE RAT
Authors: DICKMANN Z.
Published: December 2008

It is shown that the uterus of the cyclic rat can be transformed into a 'delayed-implantation' uterus (i.e. a uterus in which blastocysts are maintained in a dormant condition) by ovariectomizing females and then injecting them with 2 mg. progesterone/day, for several days. Blastocysts transferred into the uteri of females so treated remained dormant for as long as the progesterone treatment was continued. Upon injecting 1 μg. oestrone together with 2 mg. progesterone, the blastocysts implanted and developed into normal foetuses.

When blastocysts were transferred on the day of ovariectomy without previous progesterone treatment, they did not survive. Apparently ovariectomy followed by progesterone injections neutralized a uterine factor detrimental to blastocysts. The number of daily progesterone injections required to neutralize this factor depended on the day of the cycle on which ovariectomy was done. Based on the latter finding, it is postulated that the endogenous oestrogen (which fluctuates during the cycle) is the factor which renders the uterus inimical to blastocysts.
GLYCOGEN SYNTHETASE ACTIVITY IN THE RAT UTERUS
Authors: BO W. J. , MARASPIN L. E. , SMITH MAVIS S.
Published: December 2008

Glycogen synthetase, phosphorylase and glycogen were determined biochemically in the smooth muscle of the rat uterus following a single s.c. injection (10 μg.) of oestradiol dipropionate. The ovariectomized animals were killed 6, 12, 24, 48, 72 and 96 hr. after the hormone treatment. From 12 to 96 hr. glycogen synthetase activity was significantly greater than in the untreated control rats. Phosphorylase activity was significantly less than in the controls at 12 hr. and greater from 48 to 96 hr. After the initial drop, control phosphorylase values were obtained between 24 and 48 hr. From 12 to 96 hr. the glycogen concentration was greater than in the control animals.

The results show that oestrogen increased glycogen synthetase activity in the smooth muscle of the uterus soon after the hormone treatment, and with the increase in enzymic activity the glycogen concentration was also increased. They indicate that, during the early phase of glycogen synthesis, oestrogen stimulates glycogenesis by increasing glycogen synthetase activity and suppresses glycogenolysis by inhibiting phosphorylase activity. The glycogen concentration at later stages did not alter significantly, and this may have been due to the build-up and breakdown of the carbohydrate by the action of glycogen synthetase and phosphorylase, respectively.
STEROID METABOLISM OF A SERTOLI CELL TUMOUR OF THE TESTIS OF A DOG WITH FEMINIZATION AND ALOPECIA AND OF THE NORMAL CANINE TESTIS
Authors: PIERREPOINT C. G. , GALLEY JEAN McI. , GRIFFITHS K. , GRANT J. K.
Published: December 2008

The metabolism of [7α-3H]pregnenolone and [4-14C]dehydroepiandrosterone (DHA) by a Sertoli cell tumour of the testis from a dog with signs of feminization has been studied in vitro and compared with the metabolism of the normal canine testis.

The tumour formed oestrone and oestradiol-17β from DHA thus providing direct evidence for the synthesis of oestrogen by this type of neoplasm.

Relative or complete inactivity of several enzyme systems involved in the synthesis of testosterone was found in the tumour tissue, and the conversion of either precursor to testosterone was considerably less than in the normal testis.

Suggestive evidence is presented for the occurrence of steroid-specific 17α-hydroxylase and 3β-hydroxysteroid dehydrogenase-isomerase systems in canine testicular tissue.

The formation of sulphates of pregnenolone and DHA was shown both in normal and in neoplastic tissues and, in addition, the tumour either formed the sulphate of 17α-hydroxypregnenolone or caused the 17α-hydroxylation of pregnenolone sulphate.
DISTRIBUTION OF HYDROXYSTEROID DEHYDROGENASES IN THE PLACENTAE AND FOETAL MEMBRANES OF VARIOUS MAMMALS
Authors: FERGUSON M. M. , CHRISTIE G. A.
Published: December 2008

The distribution of dehydrogenases acting on 3α-, Δ5-3β-, 3β-, 11β-, 16β(androgen)-, 16β(oestrogen)-, 17β-, and 20β-hydroxysteroids in the placentae and foetal membranes of the horse, sheep, goat, cat, dog, ferret, rat, rabbit, guinea-pig and man at various stages of pregnancy is described, and some attempt is made to relate their presence in the tissues with their function.

Δ5-3β-Hydroxysteroid dehydrogenase, of particular interest in view of its important function in steroid biosynthesis, was found in the trophoblast of the horse, cat, dog and man, in the thickened maternal endothelium of the ferret placenta, in the trophoblastic giant cells of the rat, and in isolated cells in the uterine lumen of the guinea-pig in early pregnancy. The enzyme was absent from all other sites examined. Correlation is sought between the distribution of this enzyme, the steroid hormone requirements for the maintenance of pregnancy after ovariectomy, and the chemical processes of steroid production by the placentae of the species examined.
THE METABOLIC CLEARANCE RATES OF DEHYDROEPIANDROSTERONE, TESTOSTERONE AND THEIR SULPHATE ESTERS IN MAN, RAT AND RABBIT
Authors: WANG D. Y. , BULBROOK R. D. , SNEDDON A. , HAMILTON T.
Published: December 2008

The disappearance of isotopically labelled dehydroepiandrosterone, testosterone and their sulphates from the peripheral circulation of man, rabbit and rat has been investigated.

Metabolic clearance rates, distribution volumes and half-lives have been determined for these compounds in the above species.

In man, the steroid sulphates have a much lower metabolic clearance rate than the corresponding free steroids. This large difference stems from longer half-lives and lower distribution volumes of the former.

In the rabbit or rat the steroid sulphates and the appropriate free steroids do not show such marked differences in their metabolic clearance rates: the half-lives and distribution volumes are comparable.
FORMATION OF STEROIDS BY THE EQUINE FOETAL TESTIS
Authors: MacARTHUR ELIZABETH , SHORT R. V. , O'DONNELL V. J.
Published: December 2008

The testes were removed from a 9-month horse foetus and incubated with sodium [1–14C]acetate. After the addition of unlabelled steroids, the following radiochemically pure compounds were obtained: cholesterol, dehydroepiandrosterone, testosterone, androst-4-ene-3,17-dione, 17α-hydroxyprogesterone and oestrone. There was no radioactivity associated with the carrier equilenin. The yield of labelled dehydroepiandrosterone greatly exceeded that of testosterone and androst-4-ene-3,17-dione.
CONCENTRATION OF BROMINE-82 IN THE THYROID GLAND OF RATS
Authors: PAPADOPOULOS S. , MacFARLANE S. , HARDEN R. McG.
Published: December 2008

The concentration of 82Br in the thyroid gland, muscle and blood was studied in rats. In untreated animals the radioactivity per unit weight of thyroid was greater than that of muscle but less than that of blood. This radioactivity in the thyroid remained constant with time and was unaffected by perchlorate. After stimulation by endogenous thyroid-stimulating hormone (TSH) the thyroidal concentration increased to a level slightly greater than that in blood. This effect was inhibited by perchlorate. It is concluded that, while under normal conditions bromine is not concentrated by the thyroid, after stimulation by TSH there is an increased uptake by the gland. There is no evidence that bromine is metabolized further in the thyroid gland.
A COMPARISON BETWEEN THE HANDLING OF IODINE AND TECHNETIUM BY THE THYROID GLAND OF THE RAT
Authors: PAPADOPOULOS S. , MacFARLANE S. , HARDEN R. McG.
Published: December 2008

The relative affinities of the thyroid gland for 131I and 99mTcO4 and the further metabolism of these isotopes were studied in rats. 99mTcO4 is trapped to an extent almost identical to 131I in the thyroid. This process is inhibited by KClO4 and stimulated by thyroid-stimulating hormone. 99mTcO4 having been trapped is further metabolized in the thyroid gland.
THE QUANTITATIVE RELATIONSHIP OF OESTROGEN-3-GLUCOSIDURONATES AND OESTROGEN-16 (OR 17)-GLUCOSIDURONATES IN HUMAN LATE PREGNANCY URINE
Authors: HÄHNEL R.
Published: December 2008

After the separation of the conjugates on DEAE-Sephadex columns, oestrone-3-glucosiduronate, oestriol-3-glucosiduronate, oestriol-16-glucosiduronate and two 'oestradiol glucosiduronates' were determined in the urines of 20 healthy women in late pregnancy.

Oestriol-16-glucosiduronate represented on average 60%, oestriol-3-glucosiduronate 26%, oestrone-3-glucosiduronate 10% and the two 'oestradiol glucosiduronates' 2% each of the total.
THE RELATIONSHIP BETWEEN NUTRITION AND ANDROGENIC ACTIVITY IN PUBESCENT TWIN CALVES, AND THE EFFECT OF ORCHITIS
Authors: MANN T. , ROWSON L. E. A. , SHORT R. V. , SKINNER J. D.
Published: December 2008

The inhibitory effect of underfeeding on the process of male pubescence was studied in three pairs of bovine identical twin calves by feeding one twin on a normal and the other on a low plane of nutrition. As a result of malnutrition the development of the androgenic function of the testes was retarded much more markedly than spermatogenesis.

In the undernourished twin the testes contained and secreted less testosterone, and showed a lower testosterone: androstenedione ratio, than in the control animal. This nutritionally conditioned androgen deficiency was clearly reflected in a markedly retarded onset of production of fructose and citric acid by the seminal vesicles.

After castration the underfed twin responded to testosterone injections much more sluggishly than the control twin, as shown by the delayed appearance of fructose and citric acid in electrically-induced ejaculates.

Observations were also made on the effects of orchitis and cryptorchidism. Both these conditions lowered markedly the androgenic activity in the calves.
METABOLIC EFFECTS OF MONOAMINE OXIDASE INHIBITORS ON THE RAT PITUITARY
Authors: ZOR U. , SHORE J. , LOCKER D. , SULMAN F. G.
Published: December 2008

Five monoamine oxidase inhibitors (MAOI) were tested for a correlation between MAO blocking potency, the effect on somatotrophic hormone (STH) production and metabolic effects on the pituitary.

Mebanazine, N-acetyl-mebanazine and pargyline inhibited STH production, body weight gain and glucose-6-phosphate (G-6-P) dehydrogenase activity. MAOI which contain a hydrazine group (mebanazine and N-acetyl-mebanazine) also inhibited alkaline phosphatase activity as well as DNA and RNA formation in the pituitary, while pargyline, which contains an amino group, was inactive in these respects.

Iproniazid and norpargyline were inactive with regard to STH production, body-weight gain and metabolic activities of the pituitary: alkaline phosphatase activity, G-6-P dehydrogenase activity, and DNA and RNA content. This suggests a relation between the ability of an MAOI to inhibit STH production and inhibition of the phosphogluconate oxidative pathway.
THE STUDY OF OVARIAN FUNCTION IN THE EWE BY MEANS OF A VASCULAR AUTOTRANSPLANTATION TECHNIQUE
Authors: GODING J. R. , McCRACKEN J. A. , BAIRD D. T.
Published: December 2008

In order to obtain exclusive long-term access to both the arterial and venous sides of the ovarian circulation in the ewe, a technique was evolved for vascular autotransplantation of the ovary. The first stage consisted of the preparation of a carotid artery—jugular vein skin tube, with a pouch to receive the ovary and its pedicle. In the second stage, performed at least 2 months later, the left ovary and its pedicle were removed together with an aortic patch which included the orifice of the ovarian artery. The aortic patch was inlaid into the carotid artery to provide the arterial supply to the transplanted ovary; venous drainage was achieved by end-to-side anastomosis of the termination of the middle uterine vein to the jugular vein. The right ovary was removed. The transplanted ovary was shown to have an unimpaired circulation. Ovarian function was demonstrated by histological and behavioural evidence, and by demonstration of a cyclical secretion of progesterone. The rate of progesterone secretion was < 5 μg./hr. at oestrus and rose to approximately 200 μg./hr. in the luteal phase of the cycle which is within the range reported for the ovary in situ.
MODE OF ACTION OF THYROCALCITONIN
Authors: ROBINSON C. J. , MARTIN T. J. , MATTHEWS E. W. , MacINTYRE I.
Published: December 2008

The effect of nephrectomy on the response to thyrocalcitonin was studied in three groups of rats: intact animals on stock diet; parathyroidectomized rats on stock diet; and parathyroidectomized rats on high calcium, low phosphorus diet.

In intact rats and in parathyroidectomized rats on a high calcium, low phosphorus diet, nephrectomy did not alter the fall in plasma calcium and phosphate produced by thyrocalcitonin. In parathyroidectomized rats on stock diet, however, plasma calcium was not changed by the hormone, but there was an isolated fall in phosphate which was prevented by previous nephrectomy.

Experiments with 45Ca showed that when plasma calcium was lowered by thyrocalcitonin this was caused by inhibition of bone resorption.

Since the hormone also causes phosphaturia, it was concluded that there are two sites of action: bone and kidney. The skeletal effect is usually dominant and the renal effect is the major one only when the rate of bone resorption is low.
RADIOACTIVE METABOLITES IN THE LIVER AND ADRENALS OF THE HUMAN FOETUS AFTER ADMINISTRATION OF [4-14C]PROGESTERONE
Authors: GREIG MARION , MACNAUGHTON M. C.
Published: December 2008

[4-14C]Progesterone was injected into the umbilical vein of two pre-viable human foetuses. The first was dissected 14 min. after injection and the second perfused for 45 min. and then dissected. All tissues of the second foetus and the liver and adrenals of the first were examined for the presence of radioactive metabolites. Most of the steroids were present in free form, 91% and 92·5% in the liver, and 81·5% and 77% in the adrenals of the first and second foetuses, respectively. The main free steroid in the liver at 14 min. was 20α-hydroxypregn-4-en-3-one (36% of the total free steroid extracted from the liver), whereas at 45 min. it was 5β-pregnane-3α,20α-diol (69%). In the adrenals in both experiments radioactivity was present in polar compounds, 47% at 14 min. and 60% at 45 min.
THE SIGNIFICANCE OF STEROID HORMONES FOR THE DEVELOPMENT OF HYPERBILIRUBINAEMIA AND ICTERUS IN THE NEWBORN INFANT
Authors: LAURITZEN CH. , LEHMANN W.-D.
Published: December 2008

Administration of oestriol, pregnanediol or cortisone to newborn infants increased the level of unconjugated bilirubin in the blood serum. Progesterone had no such effect. Administration of oestriol, progesterone, pregnanediol and cortisone to the nursing mother also raises the bilirubinaemia of the suckling infant, presumably by the excretion of metabolites in the milk. However, in therapeutic doses, anabolic steroids, tri-iodothyronine, prednisolone and dexamethasone, which are metabolized differently, do not increase serum bilirubin. The increase of bilirubin levels by naturally occurring steroids can be explained as an effect of competition between these compounds and bilirubin for the conjugating enzyme glucuronosyl transferase in the liver of the newborn. It is suggested that the large quantities of placental and foetal steroid hormones, which have to be conjugated and excreted by the newborn in the first days of life, are the cause of hyperbilirubinaemia and icterus neonatorum. The need to conjugate these steroids and bilirubin at the same time exceeds the capacity of the immature liver to produce sufficient amounts of the conjugating enzyme during the first 3 weeks of life. The finding that administration of conjugated steroids does not elevate serum bilirubin is in favour of this hypothesis.
NATRIFERIC AND HYDRO-OSMOTIC EFFECTS ON THE TOAD BLADDER OF VASOPRESSIN ANALOGUES WITH SELECTIVE ANTIDIURETIC ACTIVITY
Authors: BENTLEY P. J.
Published: December 2008

The effects of vasopressin analogues with selective antidiuretic activity have been tested on the isolated toad bladder.

Analogues of oxytocin and 8-Arg vasopressin lacking the terminal amino group had reduced effects on water (hydro-osmotic effect) and sodium (natriferic effect) transfer across the bladder. The natriferic effect of deamino-8-Arg vasopressin was reduced 3·5 times more than its hydro-osmotic effect.

Deamino-2-Phe, 8-Arg vasopressin had a reduced hydro-osmotic action compared with deamino-8-Arg vasopressin (6 times less) while the reduction of the natriferic effect was far more pronounced (68 times).

The selective antidiuretic, compared to pressor, potency of these analogues is discussed in relation to their selective hydro-osmotic compared to natriferic potency.
THE EFFECT OF GROWTH HORMONE ON MAMMALIAN CELLS IN TISSUE CULTURE
Authors: MACA R. D. , FOLEY J. F.
Published: December 2008

The effects of human growth hormone on carbohydrate and protein metabolism have been studied in monolayer tissue cultures of mouse strain L cells and human dermal fibroblasts. In strain L cell cultures, the hormone consistently caused an increase in cell number, protein synthesis, glucose consumption, and lactic acid and keto acid accumulation in the medium; in human fibroblast cultures it increased only glucose consumption and lactic acid accumulation. It affected none of these parameters in HeLa cells.

Ovine growth hormone had no consistent effect on strain L cells but caused a striking increase in glucose consumption and lactic acid accumulation in the medium of human fibroblasts without changing cell number or protein synthesis.
THE ROLE OF THE THYROID IN THE CONTROL OF THE SLOUGHING CYCLE IN THE TOKAY (GEKKO GECKO, LACERTILIA)
Authors: CHIU K. W. , PHILLIPS J. G. , MADERSON P. F. A.
Published: December 2008

The effects of thyroidectomy, and administration of thyroxine on the skin-shedding periodicity of the normal intact, and the thyroidectomized lizard (Gekko gecko) have been studied. Thyroidectomy decreased the frequency of sloughing, whereas the injection of thyroxine into thyroidectomized (8 μg. every second day) and intact (4 μg./day) animals increased the frequency. Only the resting phase of the sloughing cycle was affected, while the proliferation-keratinization phase remained unaltered. The rôle of the thyroid in the control of sloughing is discussed.
CORTISOL BINDING TO PLASMA PROTEINS IN MAN IN HEALTH, STRESS AND AT DEATH
Authors: MURRAY D.
Published: December 2008

A method is described for determining the degree of binding by plasma proteins of cortisol by a technique of pressure ultrafiltration at 37° after addition of radioactively labelled cortisol.

In normal subjects, the mean concentration of transcortin binding sites was 5·82 × 10−7 moles/l. and the apparent association constant at 37° was 4·27 × 107 l./mole. Evidence of increased protein binding of cortisol was obtained in oestrogen-treated subjects and in women in the last 3 months of pregnancy. In the latter subjects normal levels of non-protein bound cortisol were found. The mean level of non-protein bound cortisol in eight men treated with stilboestrol was increased, but normal levels were present in four of these subjects.

The protein binding of cortisol in three patients with Cushing's syndrome and in three patients with Addison's disease was normal. Thirty-five% of cortisol in adrenal venous plasma was in the unbound state.

Increased levels of plasma 17-hydroxycorticosteroids (17-OHCS) were found in patients in stressful situations (post-operative states, infections and burns). There was no evidence of increased protein binding of cortisol.

Patients at death had increased levels of plasma 17-OHCS including three patients who had been on long-term steroid therapy. There was no evidence of increased protein binding of cortisol. On the contrary, there was some evidence of a decrease in transcortin binding sites.

It is concluded that stressful situations in man, regardless of the outcome, are associated with increased plasma levels of biologically active cortisol.
A FUNDAMENTAL DEFECT OF ADRENOCORTICAL CONTROL IN CUSHING'S DISEASE
Authors: JAMES V. H. T. , LANDON J. , WYNN V. , GREENWOOD F. C.
Published: December 2008

The plasma sugar, 11-hydroxycorticosteroid, and growth hormone responses to insulin have been studied in patients with Cushing's disease. They showed an impaired or absent plasma 11-hydroxycorticosteroid and growth hormone rise during the test, as compared with control subjects, despite the injection of amounts of insulin which produced a similar degree of hypoglycaemia. This test proved of value in differentiating between these patients and those with 'simple ' obesity since the latter usually showed a normal growth hormone and adrenal response provided an adequate amount of insulin was administered.

The patients with Cushing's disease also had an impaired adrenal response to pyrogen and to dexamethasone administration and failed to show a normal plasma 11-hydroxycorticosteroid circadian rhythm. Their response to corticotrophin, lysine vasopressin, and metyrapone, however, was normal or enhanced. It is suggested that these findings imply an abnormality of hypothalamic or cerebral control and not a primary defect of pituitary function as proposed originally by Harvey Cushing.

The growth hormone response to insulin remained impaired in four out of six patients totally adrenalectomized for Cushing's disease but was normal in three patients adrenalectomized for other reasons. It is suggested that the defect which impairs the adrenal response to insulin may, on occasions, also impair the mechanism normally operative for growth hormone secretion.
DOUBLE ISOTOPE ASSAY OF ALDOSTERONE, CORTICOSTERONE AND CORTISOL IN HUMAN PERIPHERAL PLASMA
Authors: FRASER R. , JAMES V. H. T.
Published: December 2008

A double isotope derivative assay technique for the simultaneous estimation of aldosterone, corticosterone and cortisol in human peripheral plasma is described. With this method, concentrations of the corticosteroids in plasma from adrenalectomized subjects were not significantly different from zero. Further evidence of specificity for aldosterone was obtained by measuring the disappearance rate of a single intravenous injection of unlabelled aldosterone from peripheral plasma, by demonstrating a rapid rise in aldosterone concentration in normal subjects acutely depleted of sodium, and by a comparison of aldosterone levels in patients with primary aldosteronism before and after surgical treatment. A study has also been made of the variation of the ratio of cortisol to corticosterone in normal subjects and of the effect upon this ratio of corticotrophin administration and haemorrhage.
ENZYMES OF LACTOSE BIOSYNTHESIS IN NORMAL AND HORMONALLY STIMULATED RABBIT MAMMARY GLANDS
Authors: HEITZMAN R. J.
Published: December 2008

The activities of uridine diphosphate glucose (UDPG) pyrophosphorylase and UDPG-4′-epimerase in mammary glands of rabbits were determined in late pregnancy and lactation. The activities in animals during the last 4 days of pregnancy and during days 0–4, 5–9 and 11–21 of lactation increased but the difference in the activities was significant between the days 5–9 and 11–21 only and for the pyrophosphorylase activity between days for 0–4 and 5–9.

Prolactin and cortisol acetate given daily for 3 or 5 days to rabbits pseudopregnant for 15 days caused increases in enzyme activities that were several times greater than those found in controls. The enzyme activities in the stimulated glands were similar to those observed in early lactation.

The levels of deoxyribonucleic acid/g. wet tissue were the same in the stimulated and lactating glands.
A COMPARISON OF LUTEINIZING HORMONE FROM DIFFERENT SPECIES USING THE VENTRAL PROSTATE ASSAY, WITH AND WITHOUT DELAY VEHICLE, AND THE OVARIAN ASCORBIC ACID DEPLETION ASSAY
Authors: HUTCHINSON J. S. M. , ARMSTRONG D. T. , GREEP R. O.
Published: December 2008

Six luteinizing hormone preparations were studied by the ventral prostate assay using either saline or 5% beeswax in sesame oil as the injection vehicle. The use of 5% beeswax in sesame oil increased the ventral prostate response and a steeper log-dose response curve was obtained with ovine, bovine and rat pituitary preparations. However, the responses given by equine pituitary and equine endometrial or human placental preparations were unaffected by the assay vehicle. When the relative potencies of the six preparations were assayed in terms of the ovine preparation by the ventral prostate assay and the ovarian ascorbic acid depletion assay, the ovine and bovine preparations had similar potencies; whereas the rat, equine and human preparations had apparently higher specific activities when measured by the ventral prostate assay.
STARCH-GEL ELECTROPHORESIS OF MOUSE PITUITARY GONADOTROPHINS
Authors: LLOYD H. M. , BINDON B. M. , LAMOND D. R. , MEARES J. D.
Published: December 2008

Extracts of mouse pituitary glands, prepared by homogenization and high-speed centrifugation, were separated into 16–17 fractions by preparative electrophoresis in starch gel, from which the proteins were then recovered by an electrophoretic method.

Follicle-stimulating hormone (FSH), assayed by the uterine-weight augmentation method in the hypophysectomized mouse, was confined to 2–3 adjacent portions of the gel 1 cm. wide. Luteinizing hormone (LH) assayed by the rat ovarian ascorbic-acid depletion method was recovered from three discrete regions of the gel, well separated from FSH. The most active LH fraction was of slower mobility than the FSH. Assay for 'total' gonadotrophin, using normal mouse uterine weights, disclosed active material of slow mobility, separated from the FSH fractions. A series of experiments devoted to assays of FSH separated electrophoretically from pooled mouse pituitary glands demonstrated variations in pituitary content and concentration of FSH related to sex, age, pregnancy, lactation, dietary changes and light exposure which were consistent with results of previous studies of the mouse and of the rat.
LYSOSOMAL FUNCTION IN THE CORPUS LUTEUM OF THE SHEEP
Authors: DINGLE J. T. , HAY MARY F. , MOOR R. M.
Published: December 2008

A subcellular fraction containing particles showing the characteristics of lysosomes has been isolated from the corpus luteum of the sheep. Histochemical and biochemical observations have demonstrated that the lysosomes increase in size and fragility late in the oestrous cycle. Similar changes were not found in the corpora lutea of pregnant animals.

The observed increase in lysosomal fragility is one of the earliest changes associated with luteal regression, and is thought to be of functional significance in the involution of the lutein cells.

The possible modification of lysosomal function by the production of a cell-specific lytic factor from the uterus of non-pregnant sheep is discussed.
THE EFFECTS OF OESTROGEN AND GONADOTROPHINS ON LIPID AND PROTEIN METABOLISM IN XENOPUS LAEVIS DAUDIN
Authors: FOLLETT B. K. , REDSHAW M. R.
Published: December 2008

The effect of exogenous oestrogen and follicle-stimulating hormone (FSH) on the concentration of serum lipids and protein has been investigated in the South African clawed toad, Xenopus laevis Daudin. Oestradiol-17β was implanted i.p. in mature females; the rate of absorption was 13·6 μg./day. Within 10 days the plasma concentration of all lipid components increased significantly (unesterified and esterified fatty acids, cholesterol, phospholipids). The lipid concentration tended to level out after treatment for 20 days. In contrast, oestradiol caused a steady and continued rise in the plasma protein level for up to 70 days after implantation. Electrophoresis showed that the increased protein concentration was due to the emergence of a new plasma protein or proteins with a high phosphorus, calcium and lipid content. Injections of oestradiol benzoate showed the responses to be dose-dependent; the lowest effective dose was 1·0 μg./100 g. body weight/day. Implants of oestradiol in males and hypophysectomized females resulted in a similar elevation of protein and lipid components. Mammalian FSH depressed the plasma lipid content in both untreated and oestradiol-implanted females but had no effect on the newly emergent proteins and their associated components. The results are discussed in relation to the effects of oestradiol on plasma constituents in other oviparous vertebrate groups.
THE EFFECT OF THE TIME OF OESTROGEN INJECTION ON IMPLANTATION IN OVARIECTOMIZED PREGNANT MICE
Authors: SMITH DIANNE MOORE
Published: December 2008

Results have been obtained which indicate that the time of oestrogen administration during the pre-implantation period in the ovariectomized mouse may be critical for obtaining a maximum implantation response. In one series of experiments mated mice were ovariectomized on Day 3 of pregnancy and injected with oestradiol on each of Days 3, 4, 5 and 6. In other experiments ovariectomy was performed on Day 2 and oestradiol administered on each of Days 2, 3, 4, 5 and 6. Animals in both series of experiments received progesterone continuously after ovariectomy and implantation sites were scored on Day 10. The responses were the same in both series of experiments in that the number of mice with implantation sites and the number of sites per mouse increased as oestrogen was injected on each successive day during Days 2–5. A maximum response was obtained when oestrogen was injected on Days 5–6. Several possible explanations for these findings are discussed.
THE EFFECT ON IMPLANTATION OF TREATING CULTURED MOUSE BLASTOCYSTS WITH OESTROGEN IN VITRO AND THE UPTAKE OF [3H]OESTRADIOL BY BLASTOCYSTS
Authors: SMITH DIANNE MOORE
Published: December 2008

The present experiments were undertaken in an attempt to determine whether oestrogen can directly affect implantation in the mouse embryo. To test this, mouse ova were cultured from the two-cell stage to blastocysts and transferred to ovariectomized foster mothers treated with progesterone from the time of ovariectomy. The implantation response was scored 4 days after transfer. Doses of 0·2, 0·4 and 0·8 mg. progesterone/day were tested and the effect of exogenous oestrogen at each dose level determined. The threshold dose of progesterone appears to be between 0·4 and 0·8 mg./day. Above threshold, significantly more foster mothers had implantation sites when oestrogen was injected than when it was not.

Mouse blastocysts cultured in vitro were treated with varying concentrations of oestradiol, washed, and then transferred to foster mothers receiving only progesterone. The implantation response was significantly higher when blastocysts treated with 10−8 m-oestradiol were transferred to foster mothers than when untreated control blastocysts were transferred. This finding implies that there is a direct relationship between the action of oestradiol on the blastocyst and implantation.

Additional information was obtained to show that [3H]oestradiol was taken up and bound by blastocysts cultured in vitro.
SERUM TRI-IODOTHYRONINE UPTAKE USING COATED CHARCOAL IN THE ASSESSMENT OF THYROID FUNCTION
Authors: IRVINE W. J. , STANDEVEN RUTH M.
Published: December 2008

A modification of the tri-iodothyronine T3 uptake test using coated charcoal has been developed. When the method was compared with the resin sponge test, the charcoal method was found to be more rapid, accurate and economical.

For patients who were not pregnant or receiving drugs known to affect the degree of saturation of thyroxine-binding globulin, the T3 charcoal uptake method made a good distinction between the hyperthyroid and euthyroid patients but the distinction between the hypothyroid and euthyroid patients was less satisfactory. Separation between the three groups of patients was improved by using the product of the T3 uptake and protein-bound iodine measurement (the free thyroxine index).

The [125I]T3 charcoal results are reported for 199 blood donors as normal controls. A sex difference was apparent but there was no significant variation in the age groups studied (18–60 yr.).

Thirty-seven pregnant women were studied. Calculation of the free thyroxine index did not give results within the non-pregnant euthyroid range.
A LONGITUDINAL STUDY OF THE URINARY EXCRETION OF INDIVIDUAL STEROIDS IN CHILDREN FROM 8 TO 12 YEARS OLD
Authors: TANNER J. M. , GUPTA D.
Published: December 2008

A longitudinal study was made of the urinary excretion of a number of C19 and C21 steroids in 11 healthy boys and 9 healthy girls aged 8–12 yr. Urine collections were made every 6 months, over periods ranging from 1 to 2½ yr. in different children. The excretions of most substances showed surprisingly regular increments in individual children. Differences between individual children were marked and often consistent; some children excreted high amounts of one substance and low amounts of another, and other childen the reverse. The variation between individuals in the excretion of substances such as androsterone and aetiocholanolone was reduced when the results were plotted against skeletal rather than chronological age. DHA was excreted by all subjects, but at a very low level before the skeletal age of 10 yr. The glucuronide: sulphate ratio of the 11-deoxy-17-oxosteroids fell consistently from 8 to 12 yr. whereas the ratio of 5α-: 5β-11-deoxy-17-oxosteroids increased. Boys excreted more C19 steroids than girls with the same skeletal maturity score. This comparison is physiologically more meaningful than comparing boys and girls of the same chronological age.
A SIMPLE METHOD FOR THE SEPARATE ESTIMATION OF 11-DEOXY AND 11-OXYGENATED 17-HYDROXYCORTICOSTEROIDS IN HUMAN URINE
Authors: FEW J. D.
Published: December 2008

Differential solvent extraction was substituted for chromatography in the separation of the 17-oxosteroids formed by the treatment of urinary 17-hydroxycorticosteroids with sodium borohydride and with sodium periodate. Aetiocholanolone was extracted with iso-pentane which does not extract 11-hydroxyaetiocholanolone; 11-hydroxyaetiocholanolone can then be extracted with ether. The 17-oxosteroid content of each extract was determined using the Zimmermann reaction.

Evidence for the effectiveness of the separation of the two fractions is presented. The method is discussed in terms of its reliability and clinical usefulness particularly with respect to the metyrapone test.
DIFFERENTIAL EFFECTS ON BEHAVIOUR OF THE SUBCUTANEOUS AND INTRAVAGINAL ADMINISTRATION OF OESTROGEN IN THE RHESUS MONKEY (MACACA MULATTA)
Authors: MICHAEL R. P. , SAAYMAN G. S.
Published: December 2008

The behavioural interactions between pairs of oppositely sexed, adult rhesus monkeys were studied during 1307 mating tests, each of 1 hr. duration. Females were ovariectomized and the effects of administering oestrogen subcutaneously, intravaginally, and directly to the sexual skin at different daily dose rates were compared. The subcutaneous route resulted in a greater enhancement of the overall sexual activity of the pair, and in a greater stimulation of the females' sexual invitations. In contrast, the intravaginal route of administration resulted in a greater stimulation of the males' sexual interest and of the males' mounting attempts: this occurred without a corresponding increase in female sexual receptivity and, in two pairs, resulted in increased aggression. It is concluded that communication between these primates was influenced by oestrogen-dependent changes in the vagina, and the findings point to the existence of a substance with a pheromone-like action.
STIMULATION BY HORMONES OF RNA AND PROTEIN FORMATION IN ORGAN CULTURES OF THE MAMMARY GLANDS OF PREGNANT MICE
Authors: MAYNE R. , FORSYTH ISABEL A. , BARRY J. M.
Published: December 2008

Explants of the mammary glands of 11–13 day pregnant C3H mice have been cultured in a synthetic medium with hormone additions. In cultures with insulin and corticosterone the lumina of mammary alveoli became enlarged by 48 hr. but contained little or no visible secretion; alveolar cells were not vacuolated. The rate of incorporation of [14C]adenine into RNA, and the RNA content of these explants, had fallen by 48 hr. In cultures with insulin, corticosterone and prolactin, secretion was already present in the enlarged alveolar lumina by 24 hr. and had increased in amount by 48 hr. Many alveolar cells contained secretory vacuoles. The rate of incorporation of [14C]adenine into RNA had nearly doubled by 24 hr., and the RNA content of the explants had also increased. These increases were still evident at 48 hr. The rate of incorporation of [14C]adenine into RNA was also measured at 3-hr. intervals up to 12 hr. With insulin alone, the rate remained roughly constant over the 12 hr. With insulin, corticosterone and prolactin it began to rise after 6 hr. and was finally about twice the initial value. The rate also rose to a lesser extent after 6 hr. with insulin and corticosterone. After 12 hr. with insulin, corticosterone and prolactin the rate of incorporation of [14C]lysine into proteins was also higher than with insulin alone.
METABOLISM OF [4-14C]NORETHISTERONE IN WOMEN
Authors: KAMYAB SORAYA , FOTHERBY K. , KLOPPER A. I.
Published: December 2008

After the administration of norethisterone to seven human subjects 37·4% to 80·6% of the dose was excreted in the urine within 5 days. About half of the urinary radioactivity was extractable after acid or enzymatic hydrolysis and about 80% was extracted by using a serial hydrolytic and extraction procedure. About 15% of the urinary radioactivity was present as sulphate conjugates. About 5% of the urinary radioactivity was present in acidic or phenolic compounds. No metabolism of the ethynyl group seemed to occur and the Girard reaction showed that about half of the urinary metabolites were ketonic. The metabolites in the glucuronide fraction of urine were predominantly more polar on paper chromatography than tetrahydronorethisterone, whereas in the sulphate fraction most of the metabolites had a polarity similar to the simple reduction products of norethisterone. Two days after injection the plasma still contained about 5% of the administered dose.