bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF PROLONGED FEEDING OF GOITROGENS ON THYROID FUNCTION IN RATS
Authors: BROADHEAD G. D. , PEARSON I. B. , WILSON G. M.
Published: December 2008

Graded doses of propylthiouracil, carbimazole, sulphadiazine, potassium perchlorate and potassium thiocyanate were fed to groups of rats under standardized conditions for 2 months. The rats were given 131I 24 hr. before they were killed, and the thyroid weight, the proportions of labelled iodoaminoacids, and the thyroidal iodine content were determined. All the goitrogens produced increase in thyroid size, reduction of thyroidal iodine content, and an elevation of the monoiodotyrosine: di-iodotyrosine (MIT:DIT) ratio. The tri-iodothyronine: thyroxine (T3: T4) ratio was usually increased. Irrespective of the antithyroid compound used, there was a close correlation between the decrease in thyroidal iodine content and the rise in the MIT:DIT ratio.

In further experiments, either thyroid stimulating hormone (TSH) or thyroxine were injected s.c. twice daily for 5 days. TSH decreased the MIT:DIT ratio and increased the amount of labelled T3. Thyroxine increased the MIT:DIT ratio and decreased the amount of T4.

It is suggested that when goitrogens were administered for a prolonged period, the pattern of 131I-labelling of iodoaminoacids was dependent on a balance between inhibition of synthesis caused by the goitrogen and stimulation due to TSH. There was increased production of the physiologically more economical T3 in an attempt to compensate for decreased thyroxine formation.
A COMPARISON OF CERTAIN RESPONSES OF THE VASCULAR SYSTEM OF RATS AFTER THE ADMINISTRATION OF PROGESTERONE AND OESTROGEN
Authors: FULLERTON ALICE , MORRISON J. F. B.
Published: December 2008

The effects of progesterone and oestrogens on vascular responses to oxytocin were studied in female rats. Like oestrogens, progesterone caused the appearance of a pressor response to oxytocin, and throughout pseudopregnancy oxytocin acted as a pressor substance. The pressor response to oxytocin was the same, whether progesterone and oestrogen were given singly or together. Eserine abolished the pressor response to oxytocin of rats in natural oestrus or animals treated with an oestrogen, but did not eliminate the pressor response after progesterone.
EXCRETION OF 6-OXYGENATED METABOLITES OF PROGESTERONE AND 5β-PREGNANE-3α,17α,20α-TRIOL DURING PREGNANCY
Authors: FOTHERBY K. , JAMES FRANCES , KAMYAB SORAYA , KLOPPER A. I. , WILSON G. R.
Published: December 2008

The excretion of pregnanediol, pregnanetriol and the 6-oxygenated metabolites of progesterone by fifteen women has been measured throughout pregnancy. During the first trimester the level of excretion of the 6-oxygenated metabolites varied from 0·4 to 2·2 mg./day and at the end of pregnancy the range was from 3·5 to 11·6 mg./day. During the last 6 weeks of pregnancy, pregnanediol excretion was relatively constant, whereas in seven of the patients the excretion of the 6-oxygenated metabolites continued to increase. Except at the end of pregnancy there was a close correlation between the 6-oxygenated metabolites and pregnanediol excretion. The results suggest that the 6-oxygenated metabolites and pregnanediol have the same precursor and that little, if any, of a 6-oxygenated progesterone is secreted during pregnancy.

There appears to be little increase in pregnanetriol excretion during pregnancy; six of the subjects showed a significantly higher excretion in the third trimester compared with the first trimester of pregnancy, but the values were not outside the normal range for non-pregnant subjects. The specificity of the method of Fotherby & Love (1960) for the estimation of pregnanetriol was examined when applied to pregnancy urine.

Between 1·1 and 2·4 % of administered progesterone was excreted as the 6-oxygenated metabolites. In only one of five subjects was pregnanetriol excretion increased after progesterone administration.
THE RESPONSE OF THE PITUITARY-ADRENAL SYSTEM TO A STRESSFUL STIMULUS: THE EFFECT OF CONDITIONING AND PENTOBARBITONE TREATMENT
Authors: BARRETT A. M. , STOCKHAM M. A.
Published: December 2008

Handling of intraperitoneal injections of saline, twice daily for 10 days, did not significantly affect the resting level of corticosterone in the plasma or the adrenals. The conditioning abolished the usual changes in corticosterone levels caused by further handling or injections, reduced the response to exposure to ether vapour and had no effect on the response to histamine. The effect of pentobarbitone on plasma and adrenal corticosterone concentrations was found to be dependent upon the state of the pituitary-adrenal system before administration. Pentobarbitone had no effect on the responses of the adrenal cortex to exogenous adrenocorticotrophin. The responses to ether vapour or histamine of normal rats and rats lightly sedated with pentobarbitone were not significantly different as judged by changes in plasma and adrenal corticosterone concentrations and adrenal ascorbic acid depletion. However, rats deeply anaesthetized with pentobarbitone gave responses indicative of a depression of pituitary-adrenal activity. The sites of action of pentobarbitone on the pituitary-adrenal system are discussed.
RESUMPTION OF LACTATION BY SUCKLING IN LACTATING RATS AFTER REMOVAL OF LITTERS
Authors: ÔTA K. , YOKOYAMA A.
Published: December 2008

Foster litters were given to lactating rats whose own litters had been removed 3, 5 or 9 days previously. Lactation was restored in all groups by this re-suckling procedure within a relatively short period. The restoration of lactation became more difficult as the interval between the removal of the original litters and the application of the foster litters increased.

Changes in the nucleic acid content of the mammary gland after re-suckling were investigated in the rats whose litters were removed for 3 days before re-suckling. Both the DNAP content of the gland and its weight increased steadily in proportion to the length of the period of re-suckling, so that a fairly constant DNAP concentration was maintained in the tissue. The RNAP content and the RNAP:DNAP ratio, on the other hand, increased abruptly at about the time when milk secretion was initiated by re-suckling. The DNAP content continued to increase even after the onset of restored milk secretion. These results suggest that milk secretion after re-suckling began before full restoration of the tissue structure and that growth of the glandular tissue took place concurrently with milk secretion.
THE COMPARATIVE CONTRACEPTIVE ACTIVITIES OF 10β-HYDROPEROXY-17α-ETHYNYL-4-ESTREN-17β-OL-3-ONE (SCH 10015) AND NORETHYNODREL
Authors: WATNICK A. S. , GIBSON J. , VINEGRA M. , TOLKSDORF S.
Published: December 2008

10β-Hydroperoxy-17α-ethynyl-4-estren-17β-ol-3-one (Sch 10015) was found to be less progestational than norethynodrel but equally potent as a contraceptive agent in rats. To prevent pregnancy in all the treated females, a minimum daily dose of 5 mg./kg. body weight (MPD 100) of either agent was required. At this dose, both agents had similar contraceptive mechanisms of action. They partially blocked the release of pituitary gonadotrophin and when given on the 2nd and 3rd day after coitus, i.e. after ovulation, prevented conception. Pituitary gonadotrophin inhibition is not considered to be the primary mechanism of contraception because significant numbers of rats ovulate when treated with the MPD 100 of either compound. It is concluded that the time of the primary contraceptive action of these agents at their respective MPD 100 is post-ovulatory.

It would appear from these experiments that classical progestational activity is not required for the contraceptive action of these drugs.
LEVELS OF OXYTOCIN IN THE JUGULAR VEIN BLOOD OF GOATS DURING PARTURITION
Authors: FOLLEY S. J. , KNAGGS G. S.
Published: December 2008

Oxytocin has been assayed in the jugular vein blood of goats during parturition; for comparison a few measurements were also made during pregnancy. The hormone was extracted from blood plasma by gel filtration, followed by lyophilization and then assayed in the lactating guinea-pig by the increase in intramammary pressure after intra-arterial injection.

No oxytocin could be detected in the blood during pregnancy and it was found in only one of eight goats studied during the first stage of labour. The hormone was present in appreciable quantities in blood taken during the second stage of labour, and in general, the concentration rose to a maximum when the head presented. In cases of twin births oxytocin was usually present in the blood during the birth of the second kid but at a concentration lower than during delivery of the first. After expulsion of the kid the blood oxytocin titre diminished rapidly, suggesting that secretion of oxytocin ceased as soon as the kid was born. In three experiments the total release of oxytocin during a considerable portion (2·7–11·0 min.) of the second stage labour was estimated as 223–726 m-u.

The results are consistent with the view that oxytocin is not essential for the induction of labour. Rather the hormone is released in response to stimuli arising from distension of the vagina and vulva, and by virtue of its contractile effect on the uterus assists parturition.

The half-life of intravenously injected oxytocin in the lactating goat was found to be 1 min. 22 sec. After storage of lyophilized blood extracts at −15° for 5 months milk-ejection activity had declined by only 27%.
HISTOCHEMICAL UTILIZATION OF 3α-, 6β-, 11α-, 12α-, 16α-, 16β-, 17α-, 21- AND 24-HYDROXYSTEROIDS
Authors: BAILLIE A. H. , CALMAN K. C. , FERGUSON M. M. , HART D. McK.
Published: December 2008

The histochemical utilization of 3α-, 6β-, 11α-, 12α-, 16α-, 16β-, 17α-, 21- and 24-hydroxysteroids in human and mouse testis, human placenta, mouse ovary and rat adrenal has been investigated using a coupling method and the tetrazolium salt, Nitro-BT. 3α-Hydroxysteroid dehydrogenase was present in the human Leydig cells and placental syntrophoblast, but there was little in rat adrenal zona fasciculata and in mouse ovary; the enzyme is NAD or NADP dependent. 6β-Hydroxysteroid dehydrogenase was present in human Leydig cells, mouse Leydig cells, placental syntrophoblast, ova, granulosa, theca interna, corpora lutea and interstitial tissue; it is NAD dependent. 11α-Hydroxysteroid dehydrogenase activity was very poorly developed, being NAD dependent and demonstrable only in human Leydig cells. 12α-Hydroxysteroid dehydrogenase could be demonstrated in some human Leydig cells; it was both NAD and NADP dependent. 16α-Hydroxysteroids were very poorly used by all the tissues surveyed. 16β-Hydroxysteroids gave an intense histochemical reaction with NAD in human Leydig and Sertoli cells, in placental trophoblast, in adrenal zonae glomerulosa, fasciculata and reticularis and in all ovarian tissues. 17α-, 21- and 24-hydroxysteroids were poorly utilized by human Leydig cells, but not by the other tissues. The first two were NAD dependent; 24-hydroxysteroid utilization was both NAD and NADP dependent.

The techniques used are believed to demonstrate specific hydroxysteroid dehydrogenases because of variations in pyridine nucleotide requirement and in the location in the tissues of different hydroxysteroid dehydrogenases. Moreover, stereoisomers of the same hydroxysteroid behave differently in this system. The role of steroid 5α- and 5β-dehydrogenases is discussed in connexion with the histochemical results.
EFFECTS OF ETHER ANAESTHESIA AND HAEMORRHAGE ON HORMONE STORAGE AND ULTRASTRUCTURE OF THE RAT NEUROHYPOPHYSIS
Authors: DANIEL A. R. , LEDERIS K.
Published: December 2008

Effects of ether anaesthesia with or without haemorrhage were investigated in the rat neurohypophysis in vivo and in vitro. Simultaneous observations were made on hormone release from, and the ultrastructure of, the same neural lobes.

Variable decreases in hormone content were found in the neural lobes of both anaesthetized, and anaesthetized and bled animals. A significant depletion of vasopressin (P < 0·01) occurred in the latter group when related to pressor activity/mg. wet neurohypophysial tissue.

Incubation of neural lobes removed after stimulation showed that the proportions of diffusible (free) vasopressin and oxytocin had increased. Haemorrhage under ether anaesthesia caused a significant increase in the amount of free vasopressin (P < 0·01), but not of oxytocin (P > 0·05).

Examination of control and stimulated rat posterior pituitaries with the electron microscope showed a loss of the electron-dense material from the elementary granules of the neurohypophysial nerve fibres, their swellings and their terminals after the neurones had been subjected to hormone releasing stimuli. It is suggested that disappearance of the electron-dense content of the hormone-carrying granules is not related to hormone content in the gland.

An increased number of small vesicles (250–600 Å) was observed in the nerve fibre swellings of the stimulated posterior pituitary. The distribution, origin and function of these small vesicles is discussed.
THE DIURNAL PATTERN OF PLASMA GROWTH HORMONE CONCENTRATION IN CHILDREN AND ADOLESCENTS
Authors: HUNTER W. M. , RIGAL W. M.
Published: December 2008

The diurnal pattern of plasma growth hormone levels has been investigated in nine children, without endocrinopathy, aged 8–15 yr., from whom blood samples were taken hourly during the day and 2-hourly at night.

Growth hormone was undetectable (< 1 μmg./ml.) during the first 2 hr. after meals but the levels rose thereafter to values many times higher than those found in adults. High values were consistently encountered during the night.
THE ISOLATION AND IDENTIFICATION OF EXTREMELY POLAR UNCONJUGATED STEROIDS IN HUMAN PREGNANCY URINE
Authors: DIXON W. R. , PENNINGTON G. W.
Published: December 2008

Three highly polar unconjugated Δ4-3-oxosteroids containing a 6β-hydroxyl group have been isolated from human pregnancy urine. They have been identified as 6β,17α,20β,21-tetrahydroxypregn-4-ene-3,11-dione (compound 3), 6β,11β,17α,20α,21-pentahydroxypregn-4-en-3-one (Compound 4c) and 6β,11β,17α,20β,21-pentahydroxypregn-4-en-3-one (Compound 4d). Two further steroidal compounds were found, but have not as yet been identified. The isolation procedure involved the use of thin-layer chromatography for purification of the crude urinary extracts and paper chromatography for the isolation of the individual steroids. Chemical transformations and spectroscopic analyses have been used for the identification of the individual compounds.
HYDROXYSTEROID DEHYDROGENASES IN THE HUMAN ADRENAL CORTEX
Authors: CALMAN K. C. , BAILLIE A. H. , FERGUSON M. M. , HART D. McK.
Published: December 2008

The histochemical utilization of 3α-, 3β-, 6β-, 11α-, 11β-, 12α-, 16α-, 16β-, 17α-, 17β-, 20α-, 21- and 24-hydroxysteroids by three normal adult human adrenal glands, two human foetal adrenal glands, three adrenals from patients with Cushing's syndrome and one adrenal adenoma are described.

The normal adult human adrenal showed high 16β-hydroxysteroid dehydrogenase activity in the zona glomerulosa. Activity restricted to the outer part of the zona fasciculata was recorded with 3α-, 3β-, 6β-, 11β-, 16α-, 16β-, and 17β-hydroxysteroids. The zona reticularis utilized 3α-, 3β-, 11β-, 16β- and 17β-hydroxysteroids less well than the zona fasciculata.

The adrenals of Cushing's syndrome showed activity only for 3β- and 16β-hydroxysteroid dehydrogenases; this activity was noted in all three zones. The activity pattern of the adrenal adenoma resembled that of the normal adult human adrenal except that greater activity for 16α-hydroxysteroid dehydrogenase was noted.

The foetal part of the human foetal cortex was extremely active, showing 3α-, 3β-, 6β-, 11β-, 12α-, 16α-, 16β-, 17β-, 20β- and 21-hydroxysteroid dehydrogenase activity. The definitive cortex behaved similarly to the adult gland and possessed 3α-, 3β-, 11β-, 16β- and 17β-hydroxysteroid dehydrogenases; some evidence of zoning of the definitive cortex was seen with the 16β-hydroxysteroid.

The relevance of these findings in the light of current knowledge of adrenal zonation is discussed.
BIOSYNTHESIS OF EQUILIN AND RELATED RING B UNSATURATED OESTROGENS IN PERFUSED HUMAN PLACENTA
Authors: STÁRKA L. , BREUER H. , CEDARD L.
Published: December 2008

Equilin, equilenin, 17β-dihydroequilin and 17β-dihydroequilenin were formed during perfusion of androsta-4,7-diene-3,17-dione, 3β-hydroxyandrosta-5,7-dien-17-one and 3β,7α-dihydroxyandrost-5-en-17-one through human placenta. The ring B unsaturated oestrogens were isolated and identified by paper chromatography, thin-layer chromatography, melting point determination, ultraviolet spectra, infrared spectra and various colour reactions.

The present findings show that human placental tissue is capable of forming ring B unsaturated oestrogens from neutral C-19 steroids. Of these, 3β,7α-dihydroxyandrost-5-en-17-one is a normal steroid metabolite in man. It seems, therefore, reasonable to assume that equilin and related ring B unsaturated oestrogens may occur in human pregnancy urine.
A HISTOCHEMICAL STUDY OF ENZYMES CONCERNED IN GLYCOGEN METABOLISM IN THE MYOMETRIUM OF PREGNANT AND PARTURIENT MICE
Authors: HALL KATHLEEN
Published: December 2008

Glycogen, and the activities of the enzymes phosphorylase, uridine diphosphate glucose-glycogen glucosyl transferase (UDPG-synthetase) and transglycosylase (branching enzyme) were investigated by histochemical techniques in the myometrium of intact and ovariectomized mice throughout the first pregnancy, during parturition induced by oxytocin, and on the first and second days post partum.

In intact mice, glycogen remained near the limit detectable histochemically until the end of the second week, and phosphorylase activity was almost absent in muscle fibres of the inner (circular) layer but often strong in those of the outer (longitudinal) layer. During the third week there was a progressive increase in glycogen and UDPG-synthetase in both layers and of phosphorylase in the circular layer, culminating in heavy deposits of glycogen and very strong phosphorylase activity, particularly in the circular muscle, shortly before parturition. Colour reactions with iodine suggested that at some stages of pregnancy branching enzyme activity was deficient in the circular fibres. The distribution of UDPG-synthetase activity in late pregnancy appeared to be the same as that of phosphorylase and of native glycogen, but the amount was considerably less.

During parturition, the most common pattern was of strong phosphorylase activity and heavy deposits of glycogen in the circular muscle fibres but absence or very patchy distribution of both in the longitudinal fibres. The possible mechanism for this differentiation is discussed.

Tests to separate the activities of phosphorylase a and b were carried out. Activities of both forms appeared to increase during the last part of pregnancy but there was no evidence that at parturition phosphorylase existed mainly in the a form.

Mice ovariectomized on day 14 or 15 of pregnancy were injected with a combination of progesterone, oestrogen and relaxin. Ovariectomized mice maintained on progesterone alone were resistant to oxytocin on day 19, but responsiveness could be restored by relaxin. Glycogen deposits were very small in mice given progesterone alone and appeared to be rather less than normal with all combinations of hormones. Data for phosphorylase were inconclusive.
THE DISTRIBUTION OF [1,2-3H]TESTOSTERONE IN THE TISSUES OF FEMALE RATS
Authors: WANG D. Y. , YOUNG STRETTON , BULBROOK R. D.
Published: December 2008

(1) The incorporation of [1,2-3H]testosterone in vivo into various tissues of virgin, pregnant, post-partum and tumour-bearing female rats was studied.

(2) In virgin female rats the clearance of radioactivity from mesenteric fat, mammary gland, uterus, spleen, lung and blood was similar. This similarity in the rates of clearance of radioactivity for all the tissues examined was also found for the tissues of pregnant, post-partum, and tumour-bearing rats.

(3) After the administration of [1,2-3H]testosterone different amounts of radioactivity were found in each of the tissues examined. In virgin rats the levels of incorporation were fat > uterus ≥ mammary gland > lung > blood ≥ spleen. This pattern was also obtained in post-partum and tumour-bearing animals; the tumours in the latter behaved in a similar way to normal mammary glands. In the pregnant rat, the foetus incorporated the least amount of radioactivity.
A STUDY OF THE CLASSIFICATION OF MALE HYPOGONADISM WITH OBSERVATIONS ON THE CONTROL OF 17-OXOSTEROID PRECURSORS FROM THE TESTES AND ADRENALS
Authors: CLAYTON B. E. , HUTCHINSON J. S. M. , HYDE R. D. , LONDON D. R. , MILLS I. H. , PRUNTY F. T. G.
Published: December 2008

Thirty-five male patients with hypogonadism (excluding those suffering from complete hypopituitarism) have been studied. A system of classification is outlined based on the following features: (1) the clinical picture; in particular, evidence for androgen deficiency, (2) the histology of the Leydig cells, (3) the function of the seminiferous tubules as assessed by histology and sperm counts in semen, and (4) the excretion of gonadotrophins. The patients have been classified into those with primary testicular failure and those with failure of pituitary gonadotrophin secretion; the former group includes the patients with Klinefelter's syndrome. Difficulties arose in deciding when gonadotrophin excretion was definitely subnormal because the values in the lower part of the normal range overlap some of those from patients who were obviously deficient in pituitary gonadotrophin.

Some patients showed evidence of hypothyroidism, probably related to testosterone deficiency.

The excretion of 17-oxosteroids is shown to be a poor guide to the assessment of androgen deficiency. This is partly due to the secretion of adrenal androgen, which may be greater than normal in some patients with Leydig-cell deficiency. Patients with primary Leydig-cell failure responded to stimulation by corticotrophin (ACTH) with a relatively greater increase in 17-oxosteroids than normal. Patients with deficiency of pituitary gonadotrophin responded to ACTH stimulation with a much smaller increase in 17-oxosteroid excretion than normal individuals. The evidence presented suggests that a mechanism exists for the integration of androgen production by both gonad and adrenal.
URINARY CORTISOL EXCRETION IN STRESS SITUATIONS AND IN PATIENTS WITH CUSHING'S SYNDROME
Authors: ESPINER E. A.
Published: December 2008

Measurements of urinary free cortisol were made in convalescent subjects and in patients with established Cushing's syndrome and the results compared with those in acutely ill patients, in pregnancy and in surgical patients. Cortisol was measured in urine after paper chromatography, each measurement being corrected for losses according to the recovery of added internal standard (tritiated cortisol). In a number of cases, the diurnal rhythm of cortisol excretion was also examined and the results related to plasma 11-hydroxycorticosteroid levels and measurements of renal function.

The mean 24 hr. urinary cortisol excretion in 13 convalescent subjects was 74μg. (range 35–98 μg./24 hr.) and all showed a well-marked diurnal rhythm. Patients with Cushing's syndrome excreted more than normal amounts of cortisol, even when plasma 11-hydroxycorticosteroids were in the normal range; there was a marked reversal in the diurnal rhythm of cortisol excretion. In 13 acutely ill medical patients with pyrexia, four only showed unequivocal increases in cortisol excretion although there was frequently an upset in the diurnal rhythm. The duration of the illness, rather than the severity, appeared to be an important factor so far as the response of the adrenals was concerned. A consistent increase in cortisol excretion was found in pregnancy but there was no significant difference between the day and night excretion of cortisol. The response to the stress of surgical trauma was largely dependent upon the severity of the operative procedure. The importance of emotional stress immediately before operation was shown in 4 out of 14 patients.
EFFECTS OF LUTEINIZING HORMONE AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE ON SYNTHESIS OF PROGESTATIONAL STEROIDS BY RABBIT OVARIAN TISSUE IN VITRO
Authors: DORRINGTON J. H. , KILPATRICK R.
Published: December 2008

Luteinizing hormone (LH) stimulated synthesis of both progesterone and 20α-hydroxypregn-4-en-3-one by rabbit ovarian tissue in vitro. Progesterone synthesis was stimulated by nicotinamide adenine dinucleotide phosphate (NADP), but 20α-hydroxypregn-4-en-3-one production was only slightly affected by NADP compared with the effect of LH. When NADP was added with glucose-6-phosphate (G-6-P) or 6-phospho-gluconate (6-P-G), no apparent stimulation of progestational steroid synthesis occurred.

Specific activity measurements suggested that stimulation of synthesis was masked by increased conversion of progestational steroids to other products.

When NADP and submaximal concentrations of LH were used together, potentiation rather than addition of effects on progesterone synthesis was found, and addition of effects with supramaximal concentrations of LH. No potentiation was found when NADP was replaced by NADP and G-6-P or 6-P-G, or by NADPH2. NADP, unlike LH, caused striking stimulation of progesterone synthesis by separated corpora lutea. It is suggested that the present results provide further support for the view that the actions of LH and NADP are related.
THE METABOLISM OF TESTOSTERONE BY TISSUE FROM NORMAL AND NEOPLASTIC MOUSE BREAST
Authors: SMITH J. A. , KING R. J. B.
Published: December 2008

The qualitative and quantitative metabolism of testosterone in vitro by normal and neoplastic breast tissues of BR6 mice has been investigated. These tissues contain a Δ4-5α steroid reductase, 3-oxosteroid reductase and 17β-hydroxysteroid oxidoreductase. Qualitatively, the pregnancy-dependent and independent tumours differ in that the latter produce androst-4-ene-3α,17β-diol (androstenediol) whereas the former do not. This metabolite could not be detected in incubations with normal mammary tissue from pregnant mice. In general, tumours were more active than normal tissue from pregnant animals. No conversion of testosterone to oestrone or oestradiol was detected.
THE ROLE OF NEUROPHYSIN IN THE TRANSPORT ANDRELEASE OF NEUROHYPOPHYSIAL HORMONES
Authors: GINSBURG M. , IRELAND M.
Published: December 2008

The distribution of neurophysin in subcellular fractions obtained by differential centrifugation of bovine neurohypophyses is essentially similar to the distribution of the hormones. The neurosecretory particle fraction contained more neurophysin than other fractions and neurophysin comprised half of its water soluble protein. Estimates were derived for the concentrations of oxytocin, vasopressin and neurophysin in neurosecretory granules.

In experiments in which neurosecretory granules were suspended in media at pH values between 6·2 and 8·0 it was found that release of hormones increased with increasing pH.

The role of neurophysin in the transport and release of neurohypophysial hormones is discussed.
CHANGES IN PLASMA ALDOSTERONE, CORTISOL, CORTICOSTERONE, AND RENIN CONCENTRATION IN A PATIENT WITH SODIUM-LOSING RENAL DISEASE
Authors: FRASER ROBERT , JAMES V. H. T. , BROWN J. J. , DAVIES D. L. , LEVER A. F. , ROBERTSON J. I. S.
Published: December 2008

A woman with recurrent urinary infection, bilateral renal calculi, and an abnormal pattern of plasma proteins was unable to reduce urinary sodium excretion when sodium intake was restricted.

When the intake of sodium was reduced depletion developed rapidly, and severe hyponatraemia was associated with increased plasma renin and aldosterone concentrations, and a less marked although definite, increase in plasma corticosterone. Plasma cortisol was unchanged during sodium depletion, although it increased normally after the administration of corticotrophin.
SERIAL ESTIMATION OF PLASMA RENIN CONCENTRATION DURING PREGNANCY AND AFTER PARTURITION
Authors: BROWN J. J. , DAVIES D. L. , DOAK P. B. , LEVER A. F. , ROBERTSON J. I. S.
Published: December 2008

Plasma renin concentration has been measured in normal women at intervals throughout pregnancy. Further measurements have been made in the days and hours before and after delivery of the foetus and placenta.

Plasma renin was consistently raised in the majority of pregnant women and did not change markedly until 24 hr. or more after delivery.

The significance of these findings is discussed.
THE DIFFERENCE IN RESPONSE BY THE MOUSE ADRENAL X-ZONE TO TROPHOBLAST DERIVED FROM TRANSPLANTED TUBAL EGGS AND UTERINE BLASTOCYSTS
Authors: KIRBY D. R. S.
Published: December 2008

Trophoblast derived from mouse eggs removed from the oviduct (tubal eggs) and transplanted to the kidney readily bring about degeneration of the adrenal X-zone in the intact female mouse. A similar amount of trophoblast from the same source was ineffective in ovariectomized mice. Trophoblast derived from transplanted uterine blastocysts, on the other hand, caused X-zone degeneration both in the intact and ovariectomized, and in prepubertally castrated males. The effect was abolished by hypophysectomy. It is suggested that trophoblast which develops from transplanted tubal eggs stimulates the pituitary to secrete a gonadotrophin which induces the interstitial ovarian tissue to secrete androgen which causes X-zone degeneration. Trophoblast from transplanted uterine blastocysts has the same effect and may additionally stimulate the secretion of adrenocorticotrophic hormone which, by direct action, would stimulate adrenal androgen production and thus produce degeneration of the X-zone.
THE EFFECT OF ALDOSTERONE ON SODIUM AND POTASSIUM DISTRIBUTION IN MAN
Authors: COX J. R. , PLATTS MARGARET M. , HORN MARGARET E. , ADAMS ROSEMARY , MILLER H. E.
Published: December 2008

Total exchangeable sodium, potassium and bromide space were measured by a triple isotope technique, and antipyrine space, body weight, plasma electrolyte concentrations and urine electrolyte excretion were determined before and after intramuscular injection of 0·5 mg. aldosterone 6-hourly for 6–8 days in nine convalescent men.

After the treatment with aldosterone there were mean increases in body weight of 2·5 kg., 2·5 1. in total body water, and of 3·0 1. in extracellular fluid volume; a slight decrease in intracellular fluid volume was not significant. The mean total exchangeable sodium increased by 463 m-equiv. and the mean cumulative urinary excretion of sodium decreased by 444 m-equiv. The sodium was retained in the extracellular fluid without significant change in exchangeable intracellular sodium. Mean total exchangeable potassium was reduced by 207 m-equiv. while mean cumulative urinary potassium excretion increased by 88 m-equiv. The potassium loss was entirely intracellular.

The main source of error arose from isotope counting. The coefficient of variation of the sample count minus the background exceeded ±3% in 18 out of 150 samples: these results were discarded. Sixteen of the inaccurate counts were due to low concentrations of sodium or potassium in the specimens.
QUANTITATIVE STUDIES ON ISOLATED PANCREATIC ISLETS OF MAMMALS: ENZYMIC HYDROLYSIS OF NUCLEOSIDE DIPHOSPHATES AND p-NITROPHENYL PHOSPHATE IN NORMAL AND CORTISONE-TREATED RATS
Authors: TÄLJEDAL I.-B. , HELLMAN B. , HELLERSTRÖM C.
Published: December 2008

Chemical micromethods and histochemical staining were employed for studies of the enzymic hydrolysis of inosine diphosphate (IDP) and adenosine diphosphate (ADP) and the non-specific acid phosphatase activity of the endocrine pancreas from normal and cortisone-treated rats. The following observations were made:

1. Enzymic dephosphorylation of IDP and ADP was maximal at about pH 8·0. Magnesium and manganese ions enhanced the phosphate liberation, the hydrolysis of ADP being more activated than that of IDP. A marked inhibition of enzyme activity towards either substrate was produced by sodium fluoride, sodium cyanide and ethylene-diaminotetraacetate. Acid phosphatase activity was maximal at about pH 5·5, a tendency for a second activity optimum was noted at about pH 4·0. Acid phosphatase activity was markedly inhibited by sodium fluoride, tartaric acid and formaldehyde.

2. Histochemical staining revealed marked enzyme activity towards IDP and ADP in the capillaries and walls of the large blood vessels throughout the pancreas, whereas the islet cells displayed a moderate reaction. The staining intensity was the same with IDP as with ADP.

3. Cortisone administration reduced the rate of cleavage of both IDP and ADP in both the endocrine and the exocrine pancreas, but the enzymic splitting of these substrates remained unchanged in the liver. Acid phosphatase activity was not influenced in any of these tissues by the steroid treatment.
ANTIDIURETIC HORMONE CONTENT OF THE HYPOTHALAMO-NEUROHYPOPHYSIAL SYSTEM AND URINARY EXCRETION OF ANTIDIURETIC HORMONE IN RATS DURING THE DEVELOPMENT OF DIABETES INSIPIDUS AFTER LESIONS IN THE PITUITARY STALK
Authors: LÁSZLÓ F. A. , de WIED D.
Published: December 2008

The antidiuretic hormone (ADH) content of the hypothalamo-neurohypophysial system (HNS) and the excretion of AD-activity in the urine has been examined after pituitary stalk lesion in rats. In the oliguric phase which developed approximately 24 hr. after stalk destruction and lasted for about 3 days, the HNS was greatly depleted of ADH and the excretion of AD-activity in the urine was much above normal.

Implantation of posterior lobes obtained from intact adult rats under the kidney capsule of stalk-lesioned animals with a manifest diabetes insipidus produced oliguria similar to that found after stalk destruction. However, the antidiuretic effect of the implant lasted somewhat longer and the amount of AD-activity excreted in the urine was twice as high as that excreted in the oliguric period after stalk destruction.

Subcutaneous injection of lysine or arginine vasopressin in various vehicles into rats with manifest diabetes insipidus showed that the effect of these preparations on water intake and urine output was independent of the dosage used but seemed to depend on the rate of absorption from the subcutaneous tissue. The results indicate a relationship between duration of action and the amount of AD-activity excreted in the urine.

Hyperosmoticity induced by the subcutaneous injection of a 15% NaCl solution failed to release ADH irrespective of the hormone content of the HNS of stalk-lesioned rats.

In a number of stalk-lesioned rats the polyuria gradually disappeared several weeks after stalk destruction. The ADH content of the hypothalamus of these animals was nearly normal, but that of the posterior lobe was only about 10 % of that of intact controls. The urinary excretion of AD-activity in these animals was about half of that of the controls. In such rats ADH could be readily released from the HNS after loading with 15% NaCl, indicating that animals with a regression of the diabetes insipidus had resumed the production of ADH.
ADRENAL SECRETION RATES OF C-19 AND C-21 STEROIDS BEFORE AND AFTER HYPOPHYSECTOMY IN THE PIG AND THE DOG
Authors: HEAP R. B. , HOLZBAUER MARGARETHE , NEWPORT HELEN M.
Published: December 2008

(1) The adrenal secretion of androgens and of some intermediates of corticosteroid biosynthesis have been studied in immature pigs and adult dogs under anaesthesia.

(2) Qualitative and quantitative analyses of the extracts of adrenal venous blood were performed by a combination of paper and gas chromatographic techniques.

(3) In both species 1 1βOH-androstenedione, pregnenolone, progesterone and 1 1βOH-progesterone were secreted under stress conditions at a mean rate of approximately 20 μg./adrenal/hr.; this was somewhat more than aldosterone secretion and about one-fiftieth of the glucocorticoid secretion.

(4) Within 2 hr. of hypophysectomy the secretion of all four compounds was decreased by more than 95%.
THE COMPOSITION OF FEMALE RAT SKIN IN RELATION TO REGION, AGE, HAIR GROWTH CYCLE AND HORMONES
Authors: EBLING F. J. , HALE PATRICIA A.
Published: December 2008

Skin from the dorsal flank of rats had a higher water content, a lower fat content per unit dry weight, and a higher hydroxyproline content, estimated as a proportion of the dry, defatted skin weight, than skin from the ventral flank.

In each region the water content decreased with age until the rats were about 80 days old and then remained relatively constant; the hydroxyproline content increased with age between 25 and 150 days, but not in a regular manner. There were no significant changes in skin fat with age in either region.

Superimposed on these changes were cyclic fluctuations which were correlated with the hair growth cycle. The water content was greatest during the latter part of the resting phase, and fell steeply during early activity of the follicles to a minimum towards the middle or in the latter part of the active phase. Fat reached a peak around the middle of the active phase and fell to a trough during the resting phase; it started to increase again well before the start of new follicular activity. Hydroxyproline fell during the early active phase to a minimum shortly after eruption of the hair, and then rose to reach a new peak in early telogen.

When the follicular period was shortened by ovariectomy or administration of thyroxine, or lengthened by implantation of oestradiol or by inhibition of the thyroid with propylthiouracil, the changes in water, fat and hydroxyproline continued, in the main, to fluctuate in phase with follicular activity, and the regional differences were substantially maintained. There was a tendency for the fluctuations to be accentuated when the periods were shortened and damped when they were lengthened.

Oestradiol accelerated the fall in skin water content which normally occurs with age, so that the ultimate low plain was achieved 25 days earlier. In propylthiouracil-treated rats the skin water content decreased more slowly than in normal rats, and had not reached a stable value by 150 days of age. Oestradiol-treated rats had more and spayed rats less skin fat at any age than normal controls. The skin fat content rose progressively when rats were treated with propylthiouracil.
THE RELATIONSHIP BETWEEN CORTICOSTERONE SYNTHESIS FROM ENDOGENOUS PRECURSORS AND FROM ADDED RADIOACTIVE PRECURSORS BY RAT ADRENAL TISSUE IN VITRO
Authors: VINSON G. P.
Published: December 2008

A kinetic study of corticosterone recovered during incubation of rat adrenal tissue with [4-14C]progesterone and [16-3H]pregnenolone shows that both its 3H: 14C ratio and its specific activity change with time throughout incubation. Corticosterone is itself metabolized, and hypotheses based on the rate of production of corticosterone may be therefore deceptive when the amount is measured at a single point in time. Thus disparities between the specific activities of products and intermediates may be expected which alone do not necessarily indicate differences between the biosynthetic pathways involved in production from endogenous precursors and those from added radioactive precursors.

Other experiments suggest that steroids in incubation media, in concentrations comparable with those found in adrenal venous plasma, do not inhibit the continued synthesis of hormones.
ENDOCRINE CONTROL OF ENDOMETRIAL SENSITIVITY DURING THE INDUCTION OF THE DECIDUAL CELL REACTION IN THE MOUSE
Authors: FINN C. A.
Published: December 2008

The decidual cell reaction (DCR) of ovariectomized mice treated with hormones and stimulated by the intrauterine injection of oil was investigated to obtain information about the control of uterine sensitivity during implantation. Three factors were studied; oestrogen given at the time of oestrus, progesterone and oestrogen given at the time of the nidatory surge.

For the induction of the DCR by oil both 'oestrous' oestrogen and 'nidatory surge' oestrogen were essential, whereas neither were necessary for the traumatic DCR. The quantity of nidatory surge oestrogen was very critical; 0·01 μg. were effective, 0·0625 μg. inhibitory. There was no quantitative interaction between nidatory surge oestrogen and progesterone, indicating that in this situation the two hormones are acting independently. The optimum time interval between initiating the oestrogen surge and injecting the oil was between 4 and 8 hr.

No response was obtained when the oestrogen surge was produced and the stimulus applied on the second day of treatment with progesterone; maximal responses were obtained on the fourth and fifth day and a reduced response on the seventh day. After an oestrogen surge on the fourth day, it was not possible to elicit an oil DCR to a further dose of oestrogen on the fifth day, indicating that the period of sensitivity induced by the surge on the fourth day is followed by a period of refractoriness.
THE EFFECT OF ADENOHYPOPHYSECTOMY ON THE EXTRARENAL AND RENAL EXCRETION OF THE SALINELOADED DUCK (ANAS PLATYRHYNCHOS)
Authors: WRIGHT A. , PHILLIPS J. G. , HUANG D. P.
Published: December 2008

Domestic ducks were adenohypophysectomized and 2–3 weeks later were loaded with hypertonic saline. Normal intact ducks and sham-operated ducks were similarly treated. For 2 hr. nasal gland secretion was almost completely inhibited (0·20 g.) in the adenohypophysectomized ducks and was significantly reduced (4·93 g.) in the sham-operated ducks compared with the normal intact controls (14·74 g.).

When the renal response of the adenohypophysectomized ducks was compared with that of the normal intact controls no significant difference was found as far as volume of urine and concentration of Na+ and K+ were concerned. When compared with sham-operated controls, however, these values were significantly lower in adenohypophysectomized ducks.

The adrenal weight was not significantly reduced in the adenohypophysectomized ducks, but the weights of thyroid, nasal gland and testis decreased significantly. Histological examination of the adrenal glands of the adenohypophysectomized ducks showed that the central regions were atrophic while the peripheral regions remained normal. Nasal glands, thyroid glands and testes were also examined.

It is concluded that the adenohypophysis plays a major part in regulating extrarenal excretion.
IODINE EXCRETION IN URINE, SALIVA, GASTRIC JUICE AND SWEAT IN DEHALOGENASE DEFICIENCY
Authors: PAPADOPOULOS S. , MacFARLANE S. , HARDEN R. McG. , MASON D. K. , ALEXANDER W. D.
Published: December 2008

The excretion of iodine in urine, saliva, gastric juice and sweat has been studied by using 131I-labelled monoiodotyrosine in a patient with the dehalogenase type of dyshormonogenesis. Iodinated components 'x', iodide, monoiodotyrosine and 'y' were found in the urine. A previously undescribed component (compound 'u') accounted for a large fraction of the urinary radioactive iodine. Organic iodinated compounds were not excreted in the saliva. Only inorganic iodide was found in the gastric juice. No organic iodine was detected in the sweat. The plasma inorganic iodine (PII) derived from salivary iodine measurements gave low values indicative of iodine deficiency. The PII values obtained from the urinary iodine were falsely high due to the presence of organic iodinated compounds.
ARTERIAL CONCENTRATION, OVARIAN SECRETION AND MAMMARY UPTAKE OF PROGESTERONE IN GOATS DURING THE REPRODUCTIVE CYCLE
Authors: HEAP R. B. , LINZELL J. L.
Published: December 2008

Plasma progesterone concentration was measured in arterial, jugular, mammary venous and ovarian venous blood of 20 goats, together with measurements of mammary and ovarian blood flow.

The level in arterial plasma in conscious normal and in castrated males was less than 2·6 ng./ml.; in anoestrous and oestrous females it was 3·4 ± 0·8 (s.e.) ng./ml. In the luteal phase of the ovarian cycle the level rose to 10·7 ± 2·2 ng./ml. and during pregnancy it remained above 10 ng./ml. until near term. In a goat that aborted at 15 weeks of pregnancy no progesterone was detected 3 days before or at the time of abortion.

When an active corpus luteum was present in the ovaries, the mammary venous level of progesterone was lower than the arterial concentration in 38 out of 44 instances, the mean difference being 23 ± 4% of the arterial level. In two goats the concentration in jugular vein blood was 80 and 85% of the arterial level but the mammary venous levels were lower still (57 and 75 % of the arterial concentration, respectively). In three goats sampled repeatedly during the whole reproductive cycle, simultaneous measurement of mammary blood flow showed that during pregnancy the udder was taking up to 2–30 ng. progesterone/min./10 g. tissue from the plasma. In a fourth, much older goat (in early pregnancy, but not lactating), the uptake was consistently lower. In all four animals the arteriovenous difference was linearly related to the arterial plasma concentration (r = 0·84).

In ovarian venous blood, collected under spinal anaesthesia, the plasma concentration was not significantly different from that in peripheral blood during anoestrus and oestrus, but when active corpora lutea were present the concentration was 620–1600 ng./ml. Simultaneous measurement of ovarian venous outflow suggested that 9–10·5 mg. progesterone/day was being produced by the ovaries, and about 20 % of this was taken up by the udder.

Peripheral blood progesterone levels were unaffected by chasing the animal but were raised by spinal anaesthesia and were raised still further after laparotomy.
THE METABOLISM OF [1,2-3H]17α-METHYLTESTOSTERONE IN HUMAN SUBJECTS
Authors: QUINCEY R. V. , GRAY C. H.
Published: December 2008

The metabolism of [1,2-3H] 17α-methyltestosterone (MeT) has been studied in adult human subjects, most of whom had cancer of the breast.

The rates of disappearance of MeT from plasma and of the appearance of metabolites of MeT in plasma have been measured after intravenous injection of [1,2-3H]MeT. In addition, the rate of appearance of [1,2-3H]MeT and of metabolites of MeT in urine and in faeces has been measured after intravenous injection of [1,2-3H]MeT and in urine after oral administration of the steroid. The results show that MeT is metabolized more slowly than testosterone.

Identification of metabolites of MeT which were isolated from the urine of patients to whom this steroid was administered has been attempted. Three compounds, 17α-methyl-5β-androstane-3α,17β-diol (tetrahydro-MeT), 17α-methyl-5α-androstane-3α,17β-diol (allotetrahydro-MeT) and unchanged MeT have been identified, three other compounds have been partially characterized and several others have been isolated. The most abundant metabolites of MeT are hydroxylated compounds reduced in ring A.
THE EFFECT OF BLOOD-BORNE FACTORS ON ADRENAL STEROID SYNTHESIS IN THE GOLDEN HAMSTER (MESOCRICETUS AURATUS NEHRING)
Authors: WHITEHOUSE BARBARA J. , VINSON G. P. , JANSSENS P. A.
Published: December 2008

Incubation of hamster adrenal tissue in Krebs bicarbonate Ringer solution gave rapid conversion of added [4-14C]cortisol to cortisone. Moreover, incubation in Ringer solution with [4-14C]progesterone as precursor invariably yielded cortisone in greater amounts than cortisol. On the other hand it has been confirmed that cortisol is the major free ultraviolet absorbing steroid in the adrenal venous blood of the hamster. Incubation of adrenal tissue with [4-14C]progesterone in hamster whole blood gave relatively greater amounts of cortisol which were more in keeping with the findings in vivo. This suggested that the blood contains factors which affect the cortisone-cortisol equilibrium by modifying adrenal enzyme activity. Some reduction of [3H] cortisone to cortisol was also observed during incubation with blood alone.