bluuebunny/crossref_metadata_2025 huggingface dataset:
SOME ASPECTS OF THE METABOLISM AND DISPOSITION OF BETAMETHASONE
Authors: Murphy D. , West H. F. , Bethel A. M.
Published: December 2008

Following the administration of 4 mg of tritiated betamethasone, with specific activity 75 μc/mg, the concentration of betamethasone and some of its metabolites were measured repeatedly in saliva, plasma and urine. The finding of particular interest was the metabolism of betamethasone within the salivary glands to a steroid provisionally identified as 11-oxobetamethasone. The significance of this finding and of the extra-hepatic metabolism of corticosteroids in general were discussed. Also discussed was the bearing of other findings upon the nature of the factors responsible for a cortisol analogues potency.
UNTERSUCHUNGEN ZUR BIOLOGISCHEN AKTIVITÄT DER OESTRIOL-EPIMEREN 16-EPIOESTRIOL, 17-EPIOESTRIOL UND 16,17-EPIOESTRIOL
Authors: Lauritzen C.
Published: December 2008

16-epioestriol, 17-epioestriol and 16,17-epioestriol are weaker oestrogens than oestriol as determined by the Allen-Doisy test. They are almost as active as oestriol by the intravaginal tetrazolium test and less active in the mouse uterine test. The three epimeres are »impeded oestrogenes«. The dose-effect regression line is flat over a wide range. The three metabolites, when injected together with oestradiol. competetively suppress the growth of the uterus in the rodent, stimulated by oestradiol. Moreover, when assayed on the accessory sex organs of male rats and on the comb of male chickens, they show a marked antiandrogenic action. In this respect 17-epioestriol is the most potent compound. The oestrogenic hyperaemia inducing activity of 16-epioestriol, as measured by the inhibition of the ergotamine induced necrosis of the rat tail, is similar to the activity of oestrone and oestradiol, but greater than that of oestriol. The other triols are less potent in this respect. The activity of the compounds was further tested in the vaginal opening test and the nipple test. For the first time the biological actions of 16-epioestriol and 17-epioestriol have been investigated in the human subject. Both compounds cause proliferation of the vaginal epithelium and a fern like pattern in the cervical mucus. Climacteric symptoms were favourably affected by 16-epioestriol. The three compounds are, however, without any effect on the uterine endometrium and on the excretion of hypophyseal gonadotrophin. In these respects they are similar to oestriol. Physiologically they may be of significance in a peripheral feed back mechanism acting against the primary hormones, between C-16 ketones and ketoles, in balanced reactions and as antagonists of C-16 hydroxylated androgens.
THE INITIAL METABOLISM OF 4-14C-TESTOSTERONE IN RAT. III.
Authors: ElAttar T. , Dirscherl W. , Mosebach K.-O.
Published: December 2008

Testosterone metabolites in the liver of male rats were investigated 5, 10, 20 and 30 minutes after the intraperitoneal injection of 4-14C-testosterone. At all four intervals, testosterone metabolites were found in the free and conjugated forms. The highest activity in the free and conjugated metabolites was after 10 minutes. A change in the pattern of the metabolites with time is observed. 5β-androstran-3α,17β-diol seems to be the major initial testosterone metabolite. 5β-androstran-3α-ol-17-one and an unidentified weakly polar compound are secondary conversion products of testosterone. More than 99 % of strong polar metabolites were conjugated 5β-androstran-3α,17β-diol. A new pathway of testosterone metabolism in the liver of the male rat is suggested.
STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN
Authors: Bolté E. , Mancuso S. , Eriksson G. , Wiqvist N. , Diczfalusy E.
Published: December 2008

Tracer amounts of dehydroepiandrosterone-4-14C (DHA-4-14C) and dehydroepiandrosterone-7α-3H sulphate (DHAS-7α3H) were injected simultaneously into a uterine artery in two patients twelve to fifteen minutes prior to therapeutic interruption of pregnancy at laparotomy and the amniotic fluid, foetuses, placentas and urine samples were analysed for radioactive material.

No radioactivity was found in the amniotic fluid. Regardless of the tracer administered, approximately 80 per cent of the radioactive material recovered from the placentas was in an unconjugated (free) form, whereas more than 80 per cent of the radioactivity present in the foetuses was in a conjugated form.

More than 67 per cent of the total radioactive material in the two placentas and more than 87 per cent of that in the two foetuses was present as phenolic material. Approximately half of this phenolic material was identified as oestrone (OE1) and 17β-oestradiol (OE2).

The 3H to 14C ratio of OE1 and OE2 isolated from the foetuses and urine specimens was lower than the ratio of the injected material. Corresponding 3H to 14C ratios in placental OE1 and OE2 were higher than those in foetal or urinary OE1 and OE2.

Labelled oestriol (OE3) could be detected in the placentas, but not in the foetuses. However, a 16-hydroxylated phenolic intermediate (probably 16α-hydroxyoestrone) was found in one foetus studied.

The results indicate that the DHA and DHAS of the maternal circulation can serve as direct precursors to placental OE2 and OE1 and as indirect precursors – via a foetal intermediate – to placental OE3. Both compounds reach the foetus mostly as phenolic material, the free form being a better precursor than the sulphate.

It is suggested that – around midpregnancy at least – the human placenta functions as a barrier limiting the transfer to the foetus of androgens present in the maternal circulation.
STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN
Authors: Bolté E. , Mancuso S. , Eriksson G. , Wiqvist N. , Diczfalusy E.
Published: December 2008

In connection with therapeutic abortion, in two patients tracer amounts of dehydroepiandrosterone-4-14C sulphate (DHAS-4-14C) were injected into the umbilical vein and tracer amounts of dehydroepiandrosterone-7α-3H sulphate (DHAS-7α-3H) into an antecubital vein. The over-all aromatisation of the two labelled compounds in the presence of viable foetuses was studied by analysing the radioactive metabolites excreted in the urine during a period of 6 days.

More than 25 per cent of the 3H-labelled metabolites and more than 75 per cent of the 14C-labelled metabolites recovered from the urine were phenolic in character. More than half of this phenolic radioactive material behaved as oestrone (OE1), 17β-oestradiol (OE2) and oestriol (OE3) when analysed by a modified Brown (1955) method.

The OE3 to OE1 + OE2 ratio expressed as 14C incorporated into these three fractions was significantly higher in both patients than the corresponding ratio of 3H. Also the 3H to 14C ratio of urinary OE1 significantly exceeded that of OE3.

The specific activity (S. A.) of OE3-7α-3H was by far lower than that of OE1-7α-3H, whereas the S. A. of OE3-4-14C differed much less from that of OE1-4-14C. A concept is presented describing the placental barrier to circulating androgen and the role of the placenta in the formation of OE1, OE2 and OE3.
OBESITY AND DIABETES MELLITUS IN A RAT WITH HYPOTHALAMIC LESIONS
Authors: Hausberger Franz X. , Broadhead Charles L. , Hausberger B. C.
Published: December 2008

Spontaneous diabetes mellitus was observed in a rat after injury to the ventromedial hypothalamus. At the time the diabetes was discovered, the animal was extremely obese. Fasting blood glucose was approximately 200 mg/100 ml, daily urinary glucose varied from 12 to 18 g, urinary volume from 280 to 370 ml. The islets of the pancreas showed no pathological changes. The adrenals weighed 108 mg vs. 58 mg control weight. Extensive infected skin lesions were present. The literature concerning diabetes after experimental hypothalamic injury is briefly reviewed.
CONVERSION OF SOME SYNTHETIC PROGESTINS TO OESTROGEN
Authors: Okada Hiroji , Amatsu Minoru , Ishihara Sadanao , Tokuda Gen-ichi
Published: December 2008

The effects of oral administration of synthetic progestins on the urinary oestrogen excretion were examined. 17α-ethynyl-19-nortestosterone (ENT) or 17α-ethynyl-estr-4-en-17β-ol (EEL) caused a significant rise of oestrogen output in urine. It appeared that the increased output of oestrogen was due to the conversion of ENT or EEL to ethynyl-oestradiol (EE2). Such a conversion of progestin was also observed with 17α-methyl-19-nortestosterone.

To obtain the direct evidence for the conversion of ENT to EE2, human placental homogenates were incubated in vitro first with 19-nortestosterone. The approximate yield of oestrone was 20 percent of that observed with testosterone. However, a conversion of ENT to EE2 was not detected.
IN VITRO METABOLISM OF 17α-METHYL-1 9-NORTESTOSTERONE BY FEMALE RAT LIVER HOMOGENATE
Authors: Okada Hiroji , Matsuyoshi Kichisaburo , Tokuda Gen-ichi
Published: December 2008

Incubation of 17α-methyl-19-nortestosterone-3H with female rat liver homogenate resulted in the formation of 17α-methyl-19-norandrostan-17β-ol-3-one-3H and 17α-methyl-19-norandrostane-3α,17β-diol-3H.
ZUR WIRKUNG VON ALDOSTERON UND CORTICOSTERON AUF DEN ELEKTROLYT- UND WASSERGEHALT BINDEGEWEBIGER ORGANE DER RATTE
Authors: Kriegel Walter , Dirscherl Wilhelm
Published: December 2008

An attempt was made to elucidate the distribution of electrolytes and water in connective tissues of the rat by estimating the sodium, potassium and water content in muscle, liver, skin, cartilage, aorta, tendon and serum. Animal groups treated in the following manner were compared: 1. replacement of drinking water by 0.9 % saline, 2. adrenalectomy, 3. adrenalectomy and saline, 4. adrenalectomy, saline and treatment with aldosterone (25 μg d-aldosterone-monoacetate per day), 5. adrenalectomy, saline and treatment with corticosterone (2—4 mg per day).

In the tissues investigated the electrolyte and water contents varied independently and differently in some cases. Sodium content or sodium depots respectively of the tissues were influenced in a variable manner. After administration of saline there was even a significant loss of amounts of sodium in the tendon and aorta of normal animals. After adrenal-ectomy and the development of severe insufficiency, the sodium content apart from the interstitial space of cellular tissues, was lowered only in the aorta. Moreover, adrenal insufficiency, partly compensated by administration of saline, led to loss of sodium in skin and cartilage, the latter loosing the largest relative amount.

Treatment of adrenalectomized animals with aldosterone normalized the sodium content in all the connective tissues and caused retention of sodium in the cellular tissues.

Adrenalectomized animals showed an increased water content in the connective as well as in the cellular tissues. The interstitial water especially in cartilage did not appear to be bound very tightly. After treatment with aldosterone a retention of water (without simultaneous retention of sodium in the connective tissues) could be observed in all tissues, whereas corticosterone normalized the water content in the connective tissues.

Potassium was found to be increased in all tissues of markedly deficient animals. In addition retention of K in the connective tissues (interstitial space) requires a simultaneous imbibition or loosening of the interstitial tissue.
INFLUENCE OF PROPYLTHIOURACIL AND THYROXINE ON SYNTHESIS AND SECRETION OF THYROID STIMULATING HORMONE IN THE HYPOTHYROID RAT
Authors: Bakke John L. , Lawrence Nancy
Published: December 2008

Propylthiouracil (PTU) administration to rats produced a progressive and parallel increase in the serum TSH concentration and the thyroid weight over a one year period, but the pituitary TSH content followed a biphasic curve declining markedly for 4 weeks, returning to the control level in 10 weeks and then continuing to rise until a level 5 times the control was achieved after 32 weeks. Either physiologic replacement doses or toxic doses of thyroxine (DL-T4) caused depression of serum TSH levels, significant as early as one hour after administration, followed by an increased pituitary TSH content to as much as 8 times the starting level after 10-60 hours. Thus, T4 did not appear to directly inhibit TSH synthesis during this interval. The reaction appeared to be independent of the duration of prior PTU administration or the initial size and TSH potency of the pituitary gland or the dose of T4 between 2.5 μg/100 g in one day and 40 μg/100 g daily for 4 days. PTU was not essential to this reaction because it also occurred in radiothyroidectomized rats which never received PTU. This rise in pituitary TSH during the period when TSH secretion was suppressed indicated a net pituitary TSH synthesis of as much as 61 mU/h. These values were compatible with those obtained by indirect calculations and consistent with the temporary persistence of the pre-existing TSH synthesis rate although the possibility of the stimulation of TSH synthesis by the T4 was not excluded.
SOME NOTES ON THE MODE OF ACTION OF NORETHYNODREL IN PREVENTING FERTILITY IN RATS
Authors: Saunders Francis J.
Published: December 2008

Based on absolute doses required to reach the defined end points in rats, it is proposed that inhibition of implantation or of ovulation per se cannot explain the efficacy of norethynodrel in inhibiting fecundity in female rats. The small size of the dose required to demonstrate gonadotrophin suppression indicates that this action, with consequent inhibition of follicular development, is the probable cause of the anti-fertility effect.
ANDROGEN REGULATION OF MOUSE KIDNEY RIBONUCLEASES
Authors: Kochakian Charles D. , Elsas Fred , Harrison David G.
Published: December 2008

The decrease in mouse kidney weight after castration was accompanied by a proportionate decrease in acid RNase. Administration of testosterone propionate simultaneously restored both the weight and enzyme activity to their normal levels. The total alkaline ribonuclease was not changed after either castration or androgen administration. Consequently the concentration of the enzyme changed in inverse proportion to the changes in weight.
THE EFFECT OF EXOGENOUS PRECURSORS ON ETIOCHOLANOLONE/ANDROSTERONE RATIOS IN MAN
Authors: Kirschner Marvin A. , Lipsett Mortimer B.
Published: December 2008

The effect of the ingestion of large amounts of precursors of urinary androsterone (A) and etiocholanolone (E) on the E/A ratio was explored. Dehydroepiandrosterone (DHEA) in doses of 1000 mg daily resulted in elevation of the E/A ratios from 0.8 to 2.8 by the third day. The E/A ratio remained near 1.0 after the same amount of testosterone and androstenedione. Triiodothyronine administration blocked the E/A changes seen after DHEA. Significant differences were also noted in the modes of conjugation of A and E and in epiandrosterone excretion after DHEA, androstenedione and testosterone. The data suggest that metabolism of the three precursors does not proceed entirely via the presumed intermediate, androstenedione. The role of enteric metabolism of ingested precursor was examined and found to be of minor importance.
CUSHING'S SYNDROME WITH ATYPICAL BIOCHEMICAL RESULTS
Authors: Harden R. McG. , Forrest A. P. M.
Published: December 2008

A case of Cushing's syndrome is described with bilateral adrenal hyperplasia. Basal excretion of urinary total 17-OHCS and 17-KS were within the normal range, but the excretion of 17-OHCS was not suppressed by 16 mg dexamethasone daily in divided doses for five days. The adrenal glands were stimulated normally by corticotrophin and the hypophysis by cortisol lack. The blood corticotrophin was estimated to be not significantly different from the levels found in normal persons. It is concluded that the failure of suppression indicates either that the adrenal glands were functioning in part autonomously or more likely that the pituitary corticotrophin regulating mechanism was more completely disturbed than is usually found in Cushing's syndrome, due to bilateral adrenal hyperplasia.
SOME ASPECTS OF STEROID BIOSYNTHESIS IN HUMAN OVARIAN TISSUE
Authors: Forleo Romano , Collins William P.
Published: December 2008

A method is described for the incubation of small amounts of human ovarian tissue with isotopically labelled steroid substrates in the presence of ovine F. S. H. The products are analysed by paper chromatography after preliminary purification by silica gel chromatography and determined by liquid scintillation counting. The method has been applied to samples of ovarian tissue, using 14C-progesterone, 14C-androst-4-enedione and 14C-testosterone as substrates. The tissues were also examined histologically. The results reveal differences in steroid transformations between the various components of pre- and post-menopausal ovarian tissue.
PITUITARY GONADOTROPHIN INHIBITORY ACTION OF NEUTRAL STEROIDS
Authors: Kind Fred A. , Dorfman Ralph I.
Published: December 2008

Thirty-one neutral steroids have been studied for their anti-gonadotrophic activity in a parabiosis test using castrated male and intact female rats. The previous observation that the anti-pituitary activity of certain steroids need not parallel the androgen activity and is frequently correlated with the levator ani activity has been confirmed.

By the subcutaneous injection route, compared to testosterone 100, the following relative anti-pituitary activities were determined: 6α-chlorotestosterone acetate (375); 6α-fluorotestosterone (350); 2-nitrilo-17α-methyl-5α-androst-2-en-17β-ol (350); 2-formyl-5α-androst-2-en-17β-ol (250); 2-hydroxymethyl-5α-androst-2-en-17β-ol (220) and 6α,17α-dimethyl-17β-hydroxy-5α-androstan-3-one (200).

Particularly favourable separations in gonadotrophin inhibition and androgenicity were found for 2-formyl-5α-androst-2-en-17β-ol, ratio 25 (testosterone ratio = 1) for 2-hydroxymethyl-5α-androst-2-en-17β-ol, ratio 11 and for 2-methyl-5α-androst-2-en-17β-ol, ratio 6.
IMMUNOCHEMICAL AND BIOLOGICAL SIMILARITY BETWEEN HUMAN LUTEINIZING HORMONE AND ONE OF THE ANTIGENIC COMPONENTS OF HUMAN CHORIONIC GONADOTROPHIN
Authors: Shahani Savitri K. , Rao Shanta Savur
Published: December 2008

Immunological investigations with human chorionic gonadotrophin (HCG) were carried out in order to characterize the antigens of HCG. Attempts were also made to find out whether HCG has antigens common to those of human luteinizing hormone (LH) and human follicle stimulating hormone (FSH) and also to ovine, bovine and porcine LH and pregnant mare serum gonadotrophin (PMSG). The results of the immunoelectrophoretic analysis carried out have indicated that one of the three antigens of HCG seems to be immunochemically similar to the antigen present in human LH. HCG was not observed to have any antigens in common with ovine, bovine and porcine LH and PMSG as revealed by the tests carried out with antiserum to HCG. The combining power and the biological activity of the antigen common to human LH and HCG were not completely destroyed by heating the hormones at 100° C for 30 minutes. These were, however, destroyed by treating the respective hormones with 30 per cent hydrogen peroxide. Haemorrhagic follicles were observed when human FSH was injected into immature mice together with human LH. Such haemorrhagic follicles were also observed in some of the mice injected simultaneously with heated LH or HCG along with human FSH. The significance of these observations are discussed.
THE EFFECT OF NORTESTOSTERONE PHENYLPROPIONATE ON COMPENSATORY HYPERTROPHY OF THE REMAINING KIDNEY AFTER UNILATERAL NEPHRECTOMY
Authors: Jelínek Jan , Veselá Hana , Valová Blanka
Published: December 2008

Forty eight hours after unilateral nephrectomy, both in non-castrated and in castrated male mice the relative dry weight of the remaining kidney increased significantly.

This compensatory hypertrophy was significantly stimulated as early as 96 hours after operation by the treatment with 19-nortestosterone phenylpropionate (= NPP) at the time of operation. The percentual increase of the kidney weight was approximately the same in non-castrated as in castrated mice. The absolute initial values as well as the resulting values 96 hours after operation were higher in non-castrated male mice than in castrated animals.

The number of cells and the DNA concentration per g tissue decreased during the period of non-stimulated compensatory hypertrophy in both groups of animals. NPP caused a still further decrease. The concentration of DNA per cell did not change.

Following non-stimulated compensatory hypertrophy, there was no change in the RNA concentration per g tissue or per cell in castrated mice. In non-castrated mice the concentration increased. NPP caused approximately the same percentual increase of RNA concentration in non-castrated as in castrated animals during the period of compensatory hypertrophy. The difference between both groups of mice in the RNA concentration in the remaining kidney following stimulation of the compensatory hypertrophy by NPP was statistically significant.
DEMETHYLIERUNG VON METHOXYÖSTROGENEN IN VITRO UND IN VIVO
Authors: Breuer H. , Knuppen Marlene , Gross D. , Mittermayer C.
Published: December 2008

The microsomal fraction of rat liver contains an enzyme system which, in the presence of NADPH2 and oxygen, demethylates 2-methoxyoestradiol-17β to 2-hydroxyoestradiol-17β. Under similar experimental conditions, 3-methoxyoestradiol-17β is demethylated to oestradiol-17β. The demethylation of 3-methoxyoestradiol-17β shows an optimum at pH 7.4 and is inhibited by β-diethylaminoethyl diphenylpropylacetate; the type of inhibition seems to be noncompetitive. The Michaelis-Menten constant for 3-methoxyoestradiol-17β was found to be 2.0 × 10−4 m. It appears that demethylation of 2- and 3-methoxyoestrogens is catalysed by a non-specific ether-cleaving enzyme system.

After intravenous injection of 20 mg of 3-methoxyoestradiol-17β into 3 patients, the excretion of oestradiol-17β, oestrone and oestriol in the urine showed a marked increase. The average yield of the 3 urinary oestrogens derived from 3-methoxyoestradiol-17β was 2.7% of the dose administered. By using corrections for metabolic and method losses, a demethylation rate of 17.5% for 3-methoxyoestradiol-17β was calculated. The concentrations of oestradiol-17β, oestrone and oestriol in bile also increased after intravenous administration of 3-methoxyoestradiol-17β. The maximum concentrations of oestrone and oestradiol-17β were found immediately after injection, whereas the maximum in the oestriol fraction occurred 4 h later. Oestrone was predominantly excreted in the sulphate fraction, but most of the oestriol was found in the glucuronoside fraction. These results suggest that demethylation of methoxyoestrogens takes place in liver.

Some of the biochemical and physiological aspects of demethylation are discussed.
LA FRÉQUENCE DES EFFRACTIONS CORTICO-SURRÉNALIENNES DANS LE TISSU ADIPEUX PÉRIGLANDULAIRE
Authors: Rosner P. , Cuendet R.
Published: December 2008

The authors have examined fifty adrenal glands obtained from routine autopsies. The outgrowth of adrenal cortical tissue into the periadrenal fat has been particularly studied.

No statistical correlation has been found between the frequency of these outgrowths and the adrenal weight, the age of the subjects, presence of a clinical hypertension, cardiac enlargement, or a malignant tumour.

The frequency (F) is, however, significantly increased in cases of cortical adrenal hyperplasia, particularly when the latter is associated with fibrinoid arteritis.
EFFECTS OF SHORT TERM ADMINISTRATION OF PHYSIOLOGICAL DOSES OF HUMAN GROWTH HORMONE IN THREE PATIENTS WITH TURNER'S SYNDROME
Authors: Almqvist S. , Hall Kerstin , Lindstedt S. , Lindsten J. , Luft R. , Sjöberg H. E.
Published: December 2008

The effect of apparently physiological doses of human growth hormone was investigated in three patients with Turner's syndrome in short term metabolic balance studies. The subjects presented an abnormal sex chromosome constitution and an increased level of sulphation factor activity in serum.

Two dose levels of hormone were used, and there appeared an anabolic response to both. No correlation with dose was obtained for any of the parameters used except for urinary magnesium, where the retention was greater with the higher dose. The sulphation factor activity of serum increased during hormone administration in the one case studied in this respect.

The urinary excretion of hydroxyproline was within the normal range in the two patients studied in this respect, and was not altered by growth hormone.

All patients had an increased urinary excretion of creatine which at present cannot be explained. The creatinuria diminished during growth hormone treatment.

The mechanism behind the retarded growth is discussed. It is suggested that a major factor might be a defect in the center for linear growth, i. e. the epiphyses that would make these less responsive to all the factors normally stimulating the growth processes in the epiphyseal zones.
CHROMATOGRAPHIC STUDIES ON 131I-LABELLED AMINO ACIDS IN HUMAN FAECES
Authors: Blomstedt B. , Neujahr H. Y.
Published: December 2008

A method is described for the extraction and purification of 131I-labelled amino acids from human faeces. The degree of purification of the extracts was sufficient for subsequent chromatographic separation on paper of the 131I-metabolites.

The method offers a means of determining 131I-thyroxine, triiodothyronine and diiodotyrosine in faeces with a reasonable degree of reliability.
OESTRIOL METABOLISM IN AN ANENCEPHALIC MONSTER
Authors: Diczfalusy E. , Barr M. , Lind J.
Published: December 2008

Oestriol-16-14C was injected into the umbilical vein of a newborn anencephalic monster and the circulating and excreted radioactive material was analysed.

Ten to twelve minutes following injection more than 98 per cent of the circulating radioactive material was in a conjugated form. More than 75 per cent of this conjugated material was identified as oestriol-3-sulphate and more than 20 per cent as oestriol-3-sulphate,16(17?)-glucosiduronate. No oestriol-16(17?)-glucosiduronate could be detected in the blood.

Less than 1.0 per cent of the radioactive material was excreted in the urine as unconjugated oestriol. Approximately 50 per cent was present as oestriol-16(17?)-glucosiduronate, more than 16 per cent as oestriol-3-sulphate and more than 25 per cent as oestriol-3-sulphate,16(17?)-glucosiduronate. At least 98 per cent of the oestrogen moiety of the various radioactive conjugates was identified as oestriol.
CORRELATION OF ADRENOCORTICAL HISTOPATHOLOGY WITH ARTERIOSCLEROSIS IN BREEDER RATS
Authors: Wexler Bernard C.
Published: December 2008

Spontaneous arteriosclerosis develops in repeatedly bred male and female rats. Virgin rats of an age comparable to breeder rats do not develop arteriosclerosis. The arteriosclerosis becomes increasingly severe with each successive breeding. In a parallel manner, the thymus gland involutes and the adrenal glands become hypertrophied and hyperplastic with each breeding. During the early stages of the development of arteriosclerosis, the adrenal cortex shows storage of lipids. With continued breeding, the zona glomerulosa increases in width and becomes depleted of lipid. In some cases, growth of the adrenal medulla causes compression of the cortex against the capsule of the gland and the pleomorphic nature of the medullary cells resembles a phaeochromocytoma. In some female breeders with severe arteriosclerosis the adrenal cortex shows severe haemorrhage and thromboses causing marked reduction of the cortex. The histophysiological changes observed in the adrenal cortex of breeder rats are believed to be analogous to conditions seen in humans with hyperadrenocorticism or Cushing's disease. It is suggested that there may be a close correlation between the abnormal adrenal function engendered by repeated breeding and the development of the arteriosclerosis.
PROTEINS OF NORMAL AND PATHOLOGICAL HUMAN THYROID TISSUE.
Authors: Stanley P. G.
Published: December 2008

Extracts of the normal and pathological portions of two thyroid glands containing discrete malignant nodules have been fractionated with ammonium sulphate between the limits 0–30, 30–45 and 45–70% saturation. Ultracentrifugal analysis and determination of the percentage of iodine in the protein of each fraction permitted the conclusion that thyroglobulin S20,w = 18) was the sole or major iodinated protein of each extract, but that the percentage of iodine in the thyroglobulin of the malignant portion of the gland was strongly depressed in one case and almost negligible in the second case.
STUDIES OF IODINE METABOLISM IN ICELAND
Authors: Alexander W. D. , Gudmundsson Th. Veiger , Bluhm M. M. , Harden R. McG.
Published: December 2008

The relation between plasma inorganic iodine level, thyroid clearance and absolute iodine uptake of the thyroid gland has been studied in Iceland and compared with results obtained in Glasgow using identical methods. In Iceland the plasma inorganic iodine (PII) is higher than in Glasgow due to the high iodine content of the diet and the thyroid clearance lower. This adjustment is, however, incomplete, relatively high PII levels being associated with a low thyroid clearance and a raised absolute uptake by the thyroid. There was no evidence of increased hormone production as reflected in the serum PBI.
INDUCTION OF OVULATION BY HUMAN GONADOTROPHINS
Authors: Pasetto N. , Montanino G.
Published: December 2008

The results reported in the literature show that ovulation in cases of primary and secondary amenorrhoea can be induced by treatment with human gonadotrophins.

From these reports, it can be concluded that human menopausal gonadotrophins (HMG), as well as preparations from post-mortem human pituitary (HPG), are potent ovarian stimulators.

In order to avoid cyst formation, the authors of this paper used smaller doses of HMG and HCG.

The human menopausal gonadotrophin used was Pergonal-25 E 35.

In 6 cases of primary and secondary amenorrhoea, induced ovulation was followed by two pregnancies.
OOPHORECTOMY AND CORTISONE TREATMENT AS A METHOD OF ELIMINATING OESTROGEN PRODUCTION IN PATIENTS WITH BREAST CANCER
Authors: Persson Bengt H. , Risholm Lars
Published: December 2008

The urinary excretion of oestrone, oestradiol-17β, oestriol, and 17-hydroxycorticosteroids has been estimated in 55 premenopausal and 91 postmenopausal women with breast cancer at various stages of the disease before therapy. The depletion of oestrogen excretion caused by oophorectomy combined with cortisone treatment was studied in the patients with metastasising breast tumours (32 premenopausal and 56 postmenopausal subjects).

Patients with disseminating breast cancer excreted significantly larger quantities of oestriol than healthy women of the same age, whether preor postmenopausal. The excretion of oestrone and oestradiol-17β was similar in cancer patients and healthy women of corresponding age.

Oophorectomy reduced the oestrogen excretion not only in premenopausal subjects but also in quite a number of postmenopausal patients, particularly in those who were still excreting significant amounts of oestrogens. This decrease in the oestrogen output was transient and was followed by a compensatory increase, possibly of adrenal origin.

Cortisone administered within a month after the oophorectomy at a dosage of 50 mg per day rapidly depressed the secondary rise in the oestrogen output to a level of about 4 to 5 μg/24 h irrespective of the age of the patient. This excretion level was unchanged as long as cortisone was given in an adequate dose, but increased rapidly when the cortisone treatment was discontinued.

Oophorectomy combined with adequate cortisone treatment seems to offer an alternative to the extensive surgical procedures undertaken to eliminate oestrogen production in breast cancer patients.
THE CONVERSION OF 11β-HYDROXYPROGESTERONE TO CORTICOSTERONE AND OTHER STEROID FRACTIONS BY RAT AND FROG ADRENAL GLANDS
Authors: Kraulis Ilze , Birmingham Marion K.
Published: December 2008

Rat and frog adrenal glands incubated in Krebs-Ringer bicarbonate glucose solution convert added 11β-hydroxyprogesterone to corticosterone more efficiently than added deoxycorticosterone. Up to 36% of the added 11β-hydroxyprogesterone incubated with rat adrenal glands was accounted for by the increase in the corticosterone fraction. Adrenals from both animals also metabolized 11β-hydroxyprogesterone to fractions with the mobility of aldosterone and 18-hydroxycorticosterone. These findings suggest that 11β-hydroxyprogesterone may play a significant role in corticoid synthesis.
HYPOFUNCTION OF THE THYROID GLAND, DUE TO PROLONGED AND EXCESSIVE INTAKE OF POTASSIUM IODIDE
Authors: Frey Harald
Published: December 2008

Five patients are reported, who developed various degrees of thyroid hypofunction and/or goitre while taking iodide-containing mixtures for bronchial asthma. After stopping the iodide treatment, their thyroid condition returned to normal.

The clinical features of the condition are described. Particular attention has been paid to the factors responsible for the development of thyroid hypofunction. Most important among these was the prolonged, regular and high intake of iodides.

It is concluded that patients using iodide-containing medication should interrupt the intake for 2–4 weeks at a time, several times a year.

The mechanism by which iodine depresses the function of the thyroid gland is discussed.
THE FATE OF 1,2-3H CORTEXOLONE IN MAN
Authors: De Hertogh R. , Hoet J. J. , Materazzi F. , Ekka E.
Published: December 2008

1,2-3H cortexolone was injected into normal subjects and the disappearance curve of the radioactive hormone in the plasma was determined.

This follows a biexponential function, according to a digital computer analysis. The half-life values calculated for the first and the second components of the experimental curves are 4 and 24 min respectively. On the basis of a two compartment open system, in which the second compartment is assumed to be metabolically inactive, cortexolone spreads rapidly into an apparent volume of 19 l and more slowly into a total volume of 37 l.

Endogenous production rate of cortexolone was estimated from the isotope dilution of the injected hormone as determined by measurement of the specific activity of urinary tetrahydrocortexolone. The mean production rate for 4 normal subjects was calculated to be 1100 μg per day. From these data the size of the endogenous pool of cortexolone was calculated. This averages 9.3 and 9.2 μg for the first and second compartments respectively.

The experiments are discussed with regard to a possible disturbance in the steady state by the amount of cortexolone injected.
CUSHING'S SYNDROME ASSOCIATED WITH A SUPRASELLAR TUMOUR
Authors: Krieger D. T. , Krieger H. P. , Soffer L. J.
Published: December 2008

A case is described of a roentgenographically confirmed primary suprasellar tumour in a 14 year old Negro boy, who presented with the clinical and laboratory findings of Cushing's syndrome, together with hyperpigmentation, homonymous hemianopia and unilateral ptosis. This appears to be the youngest case exhibiting Cushing's sydrome secondary to this aetiology, and one of a small number in whom the tumour could be well delineated roentgenographically in the presence of an essentially normal sella. The significant endocrine abnormalities were the demonstration of increased plasma corticotrophin levels, and the failure of both pituitary suppression by dexamethasone and of adrenal stimulation by corticotrophin. The tumour was extremely sensitive to 4500 r 60Co therapy. The remission produced thus far is of two years duration.
FREE 17-HYDROXYCORTICOSTEROID LEVEL AND EOSINOPHIL CELL COUNT DURING CORTICOTROPHIN TESTS
Authors: Hortling Herman , Pekkarinen Aimo , Puupponen Eva
Published: December 2008

The effect of intravenous infusions for 5 hours of 20–25 IU corticotrophin on the free 17-OHCS content in the plasma and on the number of the eosinophil cells in the blood was studied in patients with normal adrenocortical function and in patients with allergic diseases receiving 40–60 mg cortisol daily in a dose which suppresses the function of the adrenal cortex, as well as in hypophysectomized and adrenalectomized patients. When the maximal content of free 17-OHCS during the corticotrophin infusion was above 25–30 μg/100 ml an inverse correlation with the number of eosinophils was found. When, however, the free 17-OHCS level reached in the plasma was in the normal range (< 25 μg/100 ml) or very low no correlation was found between the free 17-OHCS content in the plasma and the percentage changes in the number of eosinophils in the blood.

In general the responses in the content of free 17-OHCS in the plasma and also in the number of the eosinophil cells in the blood, to intravenous corticotrophin administration is a good indicator of the adrenocortical function.
THE SITE OF PRODUCTION OF OESTROGENIC HORMONES IN HUMAN PREGNANCY. III.
Authors: Frandsen V. Aasted , Stakemann Georg
Published: December 2008

The hormone excretion was determined in 17 cases of pregnancy with anencephalic foetus. In 16 the excretion of oestriol was about 1/10 of the normal pregnancy level and in the 11 cases in which the oestroneoestradiol excretion was estimated, this amounted to 1/4 of the normal pregnancy level.

One of the cases presented a normal excretion of oestriol and in this case, the foetal adrenals were of normal size with a normal foetal zone. In one of the cases dehydroepiandrosterone was injected intraamniotically and this resulted in an increase in the excretion of oestrogens, predominantly in the oestrone-oestradiol fraction.

The role played by the foetal adrenals in the production of oestrogens during human pregnancy is emphasized and it is suggested that they also might participate in the metabolism of oestrogens.
ANTIBODIES IN THE PIG AGAINST PIG INSULIN
Authors: Brunfeldt K. , Deckert T.
Published: December 2008

Sera from three pigs injected subcutaneously with respectively pig, ox, and horse insulin for 87 days were incubated with 131I-pig insulin and investigated for the presence of antibodies by means of immunoelectrophoresis and autoradiography.

A binding of 131I-pig insulin to the gamma globulin fraction could be demonstrated in all animals after the commencement of the injections. Thus a cross reactivity between pig and ox insulin and pig and horse insulin occurred, however, apparently to a lesser degree in the latter case. The presence of a 131I-pig insulin binding gamma fraction in the serum from the animal injected with pig insulin, indicates a formation of antibodies against pig insulin in the pig.
EFFECTS OF HUMAN MENOPAUSAL GONADOTROPHIN PREPARATIONS IN DIFFERENT BIOASSAY METHODS
Authors: van Hell H. , Matthijsen R. , Overbeek G. A.
Published: December 2008

Several gonadotrophin preparations, HMG (Human Menopausal Gonadotrophin), HPG (Human Pituitary Gonadotrophin) and NIH FSH S1 (a FSH preparation distributed by the National Institute of Health) were investigated for biological activity, using three methods of assay.

The rat augmentation test, specific for FSH, and the rat seminal vesicle weight test, specific for ICSH both gave statistically valid results. The potencies were expressed in terms of the IRP (International Reference Preparation for HMG), and the International HCG Standard respectively. The gonadotrophic activity as determined by the rat uterine weight method was expressed in terms of IRP and in terms of the International HCG Standard.

Good agreement was found between the results in the uterine weight method and the seminal vesicle test, suggesting a strong ICSH dependence for the former. On the other hand, the results of the uterine weight method and the augmentation test were not in agreement.

Consequently the rat uterine weight method must be regarded as completely unsuitable for the assay of FSH-activity.

Among the three test methods studied, the augmentation test appears to be the only one suitable for the assay of the FSH content of gonadotrophin preparations for clinical use.

Fractionation of HMG with ethanol led to preparations with high FSH activity, 200 to 300 times that of IRP, but with little ICSH activity.

Most of the ICSH was concentrated in other fractions, indicating that both hormones can be separated. In starch gel electrophoresis these fractions showed different patterns.
THE RADIOACTIVE COMPOUNDS IN VARIOUS TISSUES OF THE OVARIECTOMISED MOUSE FOLLOWING THE SYSTEMIC ADMINISTRATION OF TRITIATED OESTRADIOL AND OESTRONE
Authors: Stone G. M.
Published: December 2008

Up to 16 h after the subcutaneous injection of a physiological dose of 17β-oestradiol-6,7-3H, almost all the radioactivity in the uterus and vagina was ether soluble and moved with oestradiol in the Bush B1 and B3 chromatographic systems (Bush 1952). In the liver and blood activity was recovered in both water and ether soluble fractions, the latter containing a number of metabolites of oestradiol. No firm binding to protein could be shown in these tissues.

After the injection of oestrone most of the radioactivity in the uterus and vagina was again ether soluble but activity associated with both oestrone and oestradiol was found. The ratio of oestradiol-oestrone in these tissues increased with increasing time after injection. Possible sites of the conversion of oestradiol to oestrone are discussed.
PHYSIOLOGIC RESPONSE TO d-MANNOHEPTULOSE: STUDIES UTILIZING THE NEPHRECTOMIZED RAT
Authors: Kraicer Peretz F. , Simon Ernst
Published: December 2008

d-Mannoheptulose was injected into rats immediately after bilateral nephrectomy. Following injection of 400 mg, a hyperglycaemic plateau of blood glucose was observed between 16 and 24 hours after injection. The intensity of the hyperglycaemia was proportional to the dose between 50 and 400 mg. Calculation of mannoheptulose »space« showed that it must be stored or metabolized. Mannoheptulose action can be prolonged by nephrectomy to allow metabolic studies of several hours' duration.
PHYSIOLOGIC RESPONSE TO d-MANNOHEPTULOSE: FRUCTOSE TOLERANCE CURVES
Authors: Simon Ernst , Kraicer Peretz F.
Published: December 2008

Male rats were given fructose tolerance tests in the presence and absence of d-mannoheptulose. In the presence of mannoheptulose, fructose uptake was normal, but glucose uptake was inhibited. Insulin was able to reduce the hyperglycaemia. These findings support the hypothesis that the inhibition of glucose utilization produced by mannoheptulose is due to insulin lack.
HYPERPARATHYROIDISM AND PREGNANCY
Authors: Wagner Gorm , Transbøl Ib , Melchior Johannes C.
Published: December 2008

The obstetric and metabolic observations made in a woman suffering from hyperparathyroidism and her newborn infant are described. The significant findings were: 1) slight maternal hypercalcaemia, 2) a high calcium concentration in amniotic fluid, 3) a foetal hypercalcaemia greater than that in the mother, 4) a low serum calcium concentration during the first few weeks of life but no manifest tetany, 5) a higher than normal plasma alkaline phosphatase level in the newborn but no bone disease demonstrable by X-ray, and 6) a lower content of calcium in the mother's milk than in normal human milk. Pregnancy, labour and delivery were uneventful.

A study of the literature comprising 23 females with a minimum of 34 pregnancies during their disease, shows that these females suffered from a more severe disease than 138 patients in a consecutive series of cases of hyperparathyroidism during about the same period (1930–1960). Since the relative number of patients with bone disease has decreased during the last 10–15 years we believe that the risks for perinatal death and tetany observed in this review, i. e. about 25 and 50 per cent, respectively, are greater than would be expected in a consecutive series today.

A severe reduction in fertility is presumably not present. Labour and delivery are not interfered with, but there seems to be a tendency toward a low birth weight. Indirect evidence for renal damage and hypertension as the cause of stillbirth and neonatal death is given.

Since no case of infantile osteitis fibrosa was observed it is concluded that the maternal parathyroid hormone does not pass freely through the placental barrier.

The treatment is discussed.
EFFECTS OF CLOMIPHENE ON THE PHYSIOLOGY OF REPRODUCTION IN THE RAT
Authors: Roy Somnath , Greenblatt Robert B. , Mahesh Virendra B.
Published: December 2008

The oestrogenic and antioestrogenic actions of clomiphene were studied in rats. In the absence of oestrogen in ovariectomized animals it exerted a uterotrophic effect, whereas, in the presence of a natural oestrogen (oestradiol) this compound at the same dosage levels counteracted the uterotrophic effect of the oestrogen. In suitable doses clomiphene also counteracted the gonadotrophin suppressing and ovulation-inhibiting actions of oestradiol. The results suggest that this agent may act by competing with the natural oestrogen for the receptor sites. The possible significance of these observations to the mode of action of clomiphene in the induction of ovulation in anovulatory women is discussed.
EFFECTS OF CLOMIPHENE ON THE PHYSIOLOGY OF REPRODUCTION IN THE RAT
Authors: Roy Somnath , Mahesh Virendra B. , Greenblatt Robert B.
Published: December 2008

The uptake of intravenously administered tritiated oestradiol by the uterus and pituitary gland of untreated, as well as clomiphene pretreated immature rats was studied to elucidate the nature of the antioestrogenic action of clomiphene. The results indicate that this agent competes with the natural oestrogen for the receptor sites in the uterus and pituitary gland and prevents the entry of oestrogen to and probably displaces it from the receptor sites. The significance of these observations with respect to the ability of clomiphene for the induction of ovulation in anovulatory women is discussed.
A COMPARATIVE STUDY OF IODINE METABOLISM IN PREGNANCY, SPORADIC GOITRE AND THYROTOXICOSIS
Authors: Aboul-Khair S. A. , Crooks J.
Published: December 2008

Studies of iodine metabolism have been carried out in 15 pregnant women, 33 cases with sporadic goitre and 11 with thyrotoxicosis. A low plasma inorganic iodine was common to the three groups. In pregnancy and sporadic goitre the thyroid clearance of iodine was elevated and the absolute iodine uptake normal. A high thyroid clearance of iodine in thyrotoxicosis was associated with a high absolute iodine uptake. The results suggest that both pregnancy and sporadic goitre are physiological responses to an iodine deficiency state while the iodine deficiency state of thyrotoxicosis is secondary to increased thyroid activity.
CONTRACTION OF THE RABBIT MAMMARY STRIP IN VITRO IN RESPONSE TO OXYTOCIN
Authors: Moore Richard D. , Zarrow M. X.
Published: December 2008

The isometric contractile response to oxytocin has been studied in vitro utilizing strips of tissue from rabbit mammary glands. Responses were maximal at resting tensions of 200–400 mg/mm2. The force of contraction increased from the beginning of lactation to about 9 days post partum and then leveled off. Little or no response is noted below 15° C and the maximum response is obtained in the range of 32 to36°C. Irreversible changes begin above 41° C. As little as 0.1 mU oxytocin/ml could be detected and the dose-response curve was demonstrated statistically to be linear between the dosages of 0.5 to 10 mU oxytocin/ml. The doseresponse curve reached a plateau at about 8–11 mU/ml. Replacing sodium with potassium resulted in a logarithmic decrease of contractile force with time. This decrease was partially reversible. The strip became inexcitable in calcium free Tyrode's solution. Excitability was again established by adding calcium. Other than to oxytocin, the mammary strip responded only to acetylcholine. The effect of acetylcholine could be blocked by atropine and this treatment did not affect the response to oxytocin. The site and mechanism of action of oxytocin are discussed.