bluuebunny/crossref_metadata_2025 huggingface dataset:
DEMETHYLATION OF MESTRANOL TO ETHINYLOESTRADIOL IN VITRO AND IN VIVO
Authors: Kappus H. , Bolt H. M. , Remmer H.
Published: December 2008

The present concept is that mestranol must be demethylated to ethinyl-oestradiol in order to have oestrogenic activity. This activation of mestranol has been studied in vivo by means of radiospirometry and in vitro incubations with rat liver microsomes.

During the microsomal incubation of doubly labelled [4-14C] mestranol and [3H-methoxy] mestranol with an NADPH-regenerating system 14C-labelled ethinyloestradiol was formed as the main metabolite, which was identified by crystallization to constant specific activity. In addition, a minor metabolite was found, which had the unaltered methoxy group. The enzymatic reaction was complete after 20 min. Pre-treatment of the rats with phenobarbital caused a threefold increase in ethinyloestradiol production.

The in vivo results after application of mestranol tritiated in the methoxy group show an increase of the body water specific activity up to a maximum on the 2nd day. In the control rats 34.5% and in phenobarbital pre-treated rats 47.7% of the tritium was metabolized to body water. DDT-pre-treatment caused a HTO production of 60%. These values represent a minimal demethylation rate for the in vivo conditions.
FEMALE ENDOCRINE CONTROL MECHANISMS DURING THE NEONATAL PERIOD
Authors: Schulz K.-D. , Harland A. , Haarmann H.
Published: December 2008

The present investigations deal with the in vivo effect of different doses of exogenous LH on the RNA- and protein-synthesis in the cerebral cortex, hypothalamus, pituitary, liver, ovary, uterus and adrenal gland of newborn guinea pigs. An increase of 3H-uridine and 3H-leucine incorporation was noted only in the ovary and the uterus. All the other organs showed no response. As early as 1 hour after the injection, LH induced a statistically significant stimulation of amino-acid incorporation into the proteins of the ovary. 2 hours later similar observations were made on the uterus reflecting an induction of uterotrophic steroid biosynthesis in the ovary in response to LH. The lowest effective dose was 5 IU LH/100 g body weight. Furthermore the experiments gave evidence for the dependence of oestrogen synthesis on the ovarian protein formation. The experimental data support the assumption that the ovary of newborn animals is not refractory to stimulation by gonadotrophic hormones. The ovary of newborn guinea pigs shows a relatively low sensitivity against RNA- and protein-synthesis inhibiting substances such as actinomycin and cycloheximide as compared to the liver. The mode of action of LH on the ovary seems to be identical during post partum life and advancing sexual maturation. The existing ovarian gonadotrophin sensitivity indicates that the hypothalamus or possibly the pituitary is primarily responsible for the functional immaturity of the endocrine ovarian control mechanisms during the neonatal period. The restricted functional capacity of the neonatal hypothalamus is characterized by the resistence of this organ to hormones regulating the hypothalamic endocrine function via short and long feedback mechanisms.
LYMPHOID INFILTRATION IN TOXIC GOITRES STUDIED WITH FINE NEEDLE ASPIRATION BIOPSY
Authors: Nilsson Göran
Published: December 2008

Cytodiagnostic fine needle aspiration biopsy specimens from toxic goitres were studied for signs of lymphoid infiltration. Comparison with histological sections of specimens obtained by surgery showed that an excess of lymphoid cells in the aspirate smears corresponded to a large number of lymphoid foci in these sections. Excess of lymphoid cells in the fine needle aspirates was also positively correlated with the occurrence of circulating thyroid antibodies against thyroglobulin and/or cytoplasmic antigen, but not with the presence of the long-acting thyroid stimulating factor, LATS. It also varied with age in that it was most common in the youngest patients and in patients between 40–55 years, while lymphoid infiltration was seldom seen in patients over 55 years. A finding of practical clinical interest was that in toxic goitres with cytological signs of lymphoid infiltration hyperthyroidism had less tendency to recur after treatment with thiocarbamide drugs than in those without such signs.
METABOLISM OF ORALLY ADMINISTERED d-NORGESTREL IN WOMEN
Authors: Hendeles S. M. , Galand N. , Schwers J.
Published: December 2008

Tritiated d-norgestrel was administered orally to five women. Urine and plasma were collected for 4 days.

In plasma the maximum tritium concentration is reached after 4 or 6 hours. This peak represents 0.2 to 0.4 per cent of the administered dose per 100 ml of plasma. After the first 24 hours more than 85 per cent of the radioactivity is in a conjugated form. The half-life of tritium in the plasma, calculated from the values obtained after the first day, varies from 27 to 55 hours.

In urine 41 to 67 per cent of the administered dose is excreted within four days, half of this during the first 24 hours. The half-life calculated from the urinary excretion of tritium is 21 hours. As much as 3.6 to 25.7 per cent of the urinary radioactivity is in an unconjugated form. In the conjugated fraction there is evidence which suggests the presence of n-acetylglucosaminides in addition to sulphates and glucuronides. At least ten metabolites of d-norgestrel can be isolated from the urine; all of them, but one, are more polar than the administered material. In one experiment 0.02 per cent of the administered dose was identified as tritiated d-norgestrel.

When unlabelled d-norgestrel (0.5 mg per day for 21 days) was administered before the ingestion of the labelled material, no significant change in the metabolic pattern could be observed apart from a possible increase of the half-life of tritium in the plasma.
LIPID COMPOSITION OF MEMBRANES OF SECRETORY GRANULES AND PLASMA MEMBRANES FROM BOVINE NEUROHYPOPHYSES
Authors: Vilhardt Hans , Hølmer Gunhild
Published: December 2008

Membranes of secretory granules and plasma membranes from bovine neurohypophyses were obtained by differential and density gradient ultracentrifugation. The purity of the fractions was checked by enzyme analysis and electron microscopy. Lipids were extracted from the membranes and were identified and quantitated by thin-layer chromatography. The major lipid components of the two membrane fractions were phosphatidylcholine, phosphatidylethanolamine, sphingomyelin and cholesterol. The fatty acid compositions of phosphatidylcholine and phosphatidylethanolamine from the membranes were further studied by gas chromatography.

The results showed that there were minor differences in the lipid composition of the two membranes, especially as to the fatty acid spectrum.
RADIOIMMUNOASSAY OF GROWTH HORMONE IN HUMAN PLASMA
Authors: Hanssen Kristian F.
Published: December 2008

The double antibody radio-immunoassay (pre-precipitation technique) for immunoreactive growth hormone (IRHGH) in human plasma has been evaluated on the basis of dilution and recovery experiments as well as by the investigation of accuracy and reproducibility. Given optimal conditions for the precipitation reaction, the method seems suitable for determination of plasma IRHGH. No cross-reaction between the precipitating antiserum and human gammaglobulin was demonstrated. Furthermore, by using an incubation period of 6 days for the reaction between 125I-HGH and the precipitated HGH antibodies, no serum factor influencing this reaction could be demonstrated. The results of the plasma IRHGH determinations were shown to be independent of the percentage of the radioactive degradation products present in the tracer HGH.

The lower detection limit is better than 0.39 ng/ml. The cumulated within-assay coefficient of variation was between 4–7% and the cumulated between-assay coefficient of variation 10%.

By using gel filtration, IRHGH in the plasma was shown to be nonhomogeneous when considering molecular weight. The normal fasting values in the ambulatory state was (Mean ± sd) ng/ml: Men 1.48 ± 0.33; women 3.83 ± 3.47. During the insulin tolerance test the mean peak plasma IRHGH was lower in children than in adults (0.02 > P > 0.01). It is suggested that this is due to the influence of sex steroids in adult subjects.
IMMUNOREACTIVE GROWTH HORMONE IN HUMAN URINE
Authors: Hanssen Kristian F.
Published: December 2008

By using a double antibody radio-immunoassay (pre-precipitation technique) for the determination of immunoreactive human growth hormone (IRHGH) in normal human urine concentrated by dialysis and lyophilization, a factor was revealed that displaces 125I-HGH from HGH antibodies. This displacement was neither due to salts nor to glucose; it is suggested that it is due to IRHGH in the urine. A linear relationship between dilution of urine and the measured IRHGH concentration was obtained. Recovery of exogenous HGH was between 70–105%. The recovery of IRHGH from different volumes of urine following dialysis and lyophilization was between 97–110%.

Plasma IRHGH and urinary IRHGH was measured simultaneously after HGH injection in a normal subject. A correlation was shown between plasma IRHGH and urinary IRHGH. In 9 normal subjects, the urinary IRHGH ranged from 28–53 ng/24 h. The excretion of urinary IRHGH was increased in acromegaly and was diminished in some, but not in all patients with adult hypopituitarism.

The urinary IRHGH was further studied by gel filtration. It was recovered in one peak corresponding to a molecular weight of approximately 20 000 – 30 000. However, in the present work it was not clarified whether the urinary IRHGH represents pituitary HGH excreted in the urine or a metabolite of high molecular weight with retained immunological properties.
PERIPHERAL PLASMA LEVELS OF OESTRONE AND PROGESTERONE IN PREGNANT COWS TREATED WITH DEXAMETHASONE
Authors: Edqvist Lars-Eric , Ekman Lars , Gustafsson Börje , Jacobsson Sten-Olof , Johansson Elof D. B. , Lindell Jan-Otto
Published: December 2008

Eight pregnant cows of the Swedish Red and White Breed were used. Four cows at 248–250 days of pregnancy received 10 or 20 mg of dexamethasone1) intramuscularly and a second dose equal to the first 3 to 6 days later. Two cows at day 75 and two cows at days 147 and 150 of pregnancy received daily injections of 40 mg of dexamethasone for 7 to 12 days. All late pregnant cows delivered living calves 12 to 68 hours after the second injection. One cow at day 150 of pregnancy aborted on the 6th day from the start of treatment. In all the other cows dead foetuses were found.

An increase in oestrone and a decrease in progesterone in peripheral blood plasma were observed in all late pregnant cows after the dexamethasone treatment. The increase in oestrone preceded the decrease in progesterone. The cow pregnant for 150 days which aborted showed decreased plasma levels of progesterone before abortion. No pronounced changes in the levels of progesterone were observed in the other three early pregnant cows. The peripheral plasma levels of oestrone showed no increase in any of the early and mid-term pregnant cows.
THE EFFECTS OF ORCHIDECTOMY AND TESTOSTERONE PROPIONATE INJECTION ON PEPTIDASE ACTIVITY IN THE MALE RAT HYPOTHALAMUS
Authors: Griffiths E. C. , Hooper K. C.
Published: December 2008

It has previously been shown that the activity of certain peptidases in the female rat hypothalamus is related to the release of luteinizing hormone releasing factor from the tissue (Griffiths & Hooper 1972a). The activity of these enzymes was investigated after orchidectomy and testosterone propionate injection to determine if a similar relationship exists in male rats. The depression in supernatant activity following orchidectomy and the elevation after testosterone treatment are interpreted as confirming this, and it is proposed that alterations in peptidase activity may be used as an index of gonadotrophin release in male as well as in female rats.
PERIPHERAL PLASMA LEVELS OF OESTROGENS AND PROGESTERONE DURING LATE BOVINE PREGNANCY
Authors: Edqvist Lars-Eric , Ekman Lars , Gustafsson Börje , Johansson Elof D. B.
Published: December 2008

The peripheral plasma levels of oestrone* were measured in 127 dairy cows of the Swedish Red and White Breed. The levels recorded during the time period from the 20th to the 35th week of pregnancy were below or about 0.1 ng per ml. After the 35th week of pregnancy the levels increased gradually and maximum levels ranging from 0.5 to 2 ng per ml were found during the last week of gestation. After parturition the levels decreased significantly to about 0.1 ng per ml or less.

Six cows were sampled daily from 8 days before until two days after parturition. The peripheral plasma levels of oestrone, oestradiol-17β and progesterone were measured. The oestrone level ranged from about 0.7 to 0.9 ng per ml during the last eight days preceding the delivery. The peripheral plasma levels of oestradiol-17β followed the same pattern as for oestrone. The concentration of oestradiol was only 10 to 20 per cent of the oestrone level. The mean peripheral plasma levels of progesterone were about 4 to 5 ng per ml during the last seven days before partus. A significant drop of the peripheral plasma level of progesterone to an average of 1.8 ng per ml occurred about 24 hours before parturition.
DIFFERENCES IN 17-OXOGENIC STEROID EXCRETION IN PREGNANCIES WITH NORMAL AND ANENCEPHALIC FOETUSES
Authors: Heys R. F. , Oakey R. E.
Published: December 2008

The 17-oxogenic steroid excretion of women pregnant with an anencephalic foetus was found to be significantly lower than that of women pregnant with a normal foetus but similar to that of non-pregnant women taking oral contraceptives containing oestrogens. It is suggested that the diminished excretion of 17-oxogenic steroids in pregnancies with an anencephalic foetus may reflect defective production of corticosteroids or their precursors by the abnormal adrenal of the anencephalic foetus.
ADRENAL AND GONADAL CONTRIBUTION TO ANDROGEN AND OESTROGEN EXCRETION IN KLINEFELTER'S SYNDROME
Authors: Frøland Anders , Frandsen V. Aasted , Johnsen Svend G.
Published: December 2008

Dexamethasone suppression tests were carried out in a group of 42 patients with Klinefelter's syndrome having a 47,XXY karyotype. Urinary androgen excretion obtained during suppression was considered to represent the gonadal contribution. The difference between pre-suppression values and suppression values was interpreted as the adrenal contribution to sex steroid excretion. It was shown that not only was the gonadal androgen production much lower in Klinefelter's syndrome than in a comparable group of normal men, but the adrenal androgen synthesis was also significantly reduced.

Adrenal dehydroepiandrosterone as against adrenal androsterone plus etiocholanolone was positively correlated in Klinefelter's syndrome in contrast to normal men. This is taken as an indication of a qualitatively altered synthesis of adrenal sex hormones in the patient group.

The oestrogen excretion was not quantitatively altered in Klinefelter's syndrome when compared with normal men. Correlation studies showed that in Klinefelter's syndrome adrenal oestrogens and adrenal DHA were uncorrelated contrary to the findings in normal men. This points towards an abnormal adrenal oestrogen synthesis in Klinefelter's syndrome.
INTERFERENCE BY SERUM PROTEINS WITH LH RADIOIMMUNOASSAY USING IMMUNOSORBENT
Authors: Reuter A. M. , Hendrick J. C. , Sulon J. , Franchimont P.
Published: December 2008

The percentage of LH* bound to antibodies that have been covalently bound to cellulose is diminished in the presence of LH-free human serum and sera from various species of animals.

Serum fractionation studies on Sephadex G 200 show that the greatest interference comes from the proteins eluted in the void volume i. e. the high molecular weight proteins. Specifically, the gamma M globulins and the α2-macroglobulins appear to play an important role, as demonstrated by tests in which these proteins were neutralized by gamma M and α2-macroglobulin antisera.
FOLLICLE STIMULATING HORMONE (FSH) AND INTERSTITIAL CELL STIMULATING HORMONE (ICSH) IN RELATION TO GAMETIC OUTPUT IN 643 MALES
Authors: Kjessler Berndt , Wide Leif
Published: December 2008

The relation between gonadotrophin secretion and average gametic output has been investigated in 643 healthy male partners of barren couples. FSH and ICSH excretion in urine were determined by means of bioassay and radioimmunoassay respectively, and FSH in serum was determined by radioimmunoassay.

The mean sperm counts were calculated for each patient from serial seminal analyses over a 12 week observation period.

The subjects were grouped according to their average gametic output and statistically significant differences were found between all mean excretion values for FSH, and for all but one pair of ICSH mean excretion values, when groups of patients with decreasing gametic output were compared. Individual assay results were, however, widely spread within each subgroup with extensive overlapping between the groups.

A general trend towards an increase in FSH as well as of ICSH secretion with decreasing gametic output was found. Thus, the mean excretion of FSH was found to be increased by 2.7 times, and the mean excretion of ICSH by 1.7 times, when azoospermic males were compared with males with a mean sperm count of 20 mill, per ml or more.

There was no evidence of accumulation of males with low or absent gonadotrophin secretion in any subgroup, and this may indicate that only few, if any, of the ordinary healthy male partners in the present couples suffered from a primary pituitary failure to secrete FSH or ICSH.

About 50 per cent of the males with increased FSH secretion and low or absent gametic output may have a selective spermatogenic failure, while the remainders are likely to suffer from a more general gonadal deficiency, since they also have a concomitant rise in ICSH.
THE CONCENTRATION OF PEROXIDASE IN NORMAL AND ADENOMATOUS HUMAN THYROID TISSUE WITH SPECIAL REFERENCE TO PATIENTS WITH PENDRED'S SYNDROME
Authors: Ljunggren Jan-Gustaf , Lindström Hans , Hjern Bo
Published: December 2008

The peroxidase content in the thyroids from two patients with Pendred's syndrome (abnormal discharge of iodide from the thyroid after perchlorate administration, congenital deafness and sporadic goitre) was investigated and compared to the content in 11 patients with normal thyroids, 22 patients with adenomatous goitres and 12 patients with diffuse toxic goitres.

The results indicate that the peroxidase contents in the patients with Pendred's syndrome are not decreased as compared to normal or nodular thyroid tissue. The results are discussed with regard to the cause of an intrathyroidal iodide organification defect. It is suggested that patients with Pendred's syndrome may have a defective hydrogen peroxide producing system.
VALUE OF SINGLE URINE SPECIMENS IN ESTIMATION OF 24 HOUR URINE IODINE EXCRETION
Authors: Frey H. M. M. , Rosenlund B. , Torgersen J. P.
Published: December 2008

The excretion of iodine both in a 24 hour urine collection and per g of creatinine in a single afternoon specimen was studied in 33 physicians and 29 nurses in Oslo. The mean 24 hour excretion in males was 216 μg/24 h and in females 165 μg/24 h.

The mean ratio between total urinary iodine excretion in 24 hours and the excretion per g of creatinine in the afternoon specimen was found to be 1.97 (sd = 0.53) in males and 1.30 (sd = 0.49) in females.

These data make it possible to calculate the mean 24 hour urinary iodine excretion in population studies on the basis of afternoon urine specimens, and also to estimate the accuracy of this calculation.

The method was used on samples of urine from 210 healthy males and 73 healthy females in Oslo (mostly industrial workers). The estimate of the mean 24 hour iodine excretion in the males was 248 μg/24 h (sem 4.5), and in the females 173 μg/24 h (sem 8).
RESPONSE OF PLASMA ALDOSTERONE TO ANGIOTENSIN II, ACTH AND POTASSIUM IN MAN
Authors: Scholer D. , Birkhäuser M. , Peytremann A. , Riondel A. M. , Vallotton M. B. , Muller A. F.
Published: December 2008

Plasma aldosterone, corticosterone, cortisol and renin activity have been measured in recumbent normal subjects (n = 3–4) following stimulation with angiotensin II, ACTH and potassium. Control studies on a regular sodium intake show that in the same subject aldosterone and renin activity exhibit no time dependent pattern from 7 a.m. to 11 a.m., while corticosterone and cortisol decrease continuously. Angiotensin II (infusion of 7 ng/kg/min over 1–3 h), ACTH (rapid iv injection of 0.5 mg β1-24 ACTH) and potassium (potassium citrate 30 mEq. po every hour for 3 h) on a regular Na intake induce a reproducible increase of aldosterone. The onset of this increase is observed within 10 min for angiotensin II and ACTH and within 60–90 min for potassium. The range of the rise in aldosterone is about 20–25 ng/100 ml for all 3 stimuli, corresponding to a 3–5 fold increase from basal values. Angiotensin II and potassium are, in the dose used, specific stimuli of aldosterone; ACTH however stimulates aldosterone, corticosterone and cortisol, but to a variable degree and with a different time-course response. On a low sodium intake, a similar aldosterone response pattern is found after stimulation with ACTH, but only exceptionally after stimulation with potassium; after both stimuli values of 55–75 ng/100 ml have been reached.
HAPTEN-RADIOIMMUNOASSAY OF PLASMA OESTRADIOL
Authors: Doerr Peter
Published: December 2008

A hapten-radioimmunoassay for plasma oestradiol is described and information about the reliability of the method is given in detail. Oestradiol-3-hemisuccinate coupled to keyhole limpet haemocyanin is used for immunization of rabbits. The antiserum utilized for the assay is characterized by its titer, affinity and specificity. Following ether extraction and NaOH-light petroleum partition oestradiol is separated from crossreacting oestrogens by TLC. Oxidation of oestradiol on the plate is prevented by mercaptoethanol. To separate free and antibody bound ligand 250 μg dextran-coated charcoal per tube is used in the presence of bovine serum gammaglobulin (1 mg/ml). The between-assay precision based on 15 different determinations of control samples from normal adult male plasma was 9.4% (C. V.). The mean reagent blank value of 31 determinations was equivalent to 0.3 pg oestradiol and the detection limit in terms of the 99% confidence limit for a single blank value, was equivalent to 4.3 pg oestradiol. A procedure for detecting plasma blanks is described. Plasma oestradiol is separated from approximately all concomitant substances originally present in the sample by enzymatic conversion into oestrone and a second TLC. No plasma blanks could be detected with respect to normal adult male plasma. Normal values for adult males based on 51 subjects were characterized by a median of 17.2 pg/ml and the 95 percentiles of 9.5–27.6.
THE EFFECTS OF CYPROTERONE ACETATE AND OESTRADIOL UPON TESTOSTERONE STIMULATED SEBACEOUS ACTIVITY IN THE RAT
Authors: Ebling F. J.
Published: December 2008

Castrated rats were implanted with testosterone and in addition treated with either cyproterone acetate or oestradiol or both. Testosterone by itself very significantly increased both sebum production and the incidence of sebaceous mitoses. Each of the other compounds significantly reduced sebum production in rats treated with testosterone. Cyproterone acetate reduced the incidence of sebaceous mitoses and the weight of the preputial glands, whereas oestradiol had neither of these effects. When both compounds were given simultaneously, their combined effect in reducing sebaceous secretion was equal to the product of their individual effects. The results reinforce the view that oestrogenic and anti-oestrogenic steroids have different points of action in the sebaceous glands, and suggest that the most effective way of reducing sebaceous activity might be to use both types of compound in combination.
RADIOIMMUNOASSAY FOR TRIIODOTHYRONINE IN HUMAN SERUM
Authors: Hüfner M. , Hesch R.-D.
Published: December 2008

A radioimmunoassay for triiodothyronine (T3) is demonstrated. Details of the T3 antibody binding reaction are discussed and the statistical data of the assay system are presented. Plasma samples were first extracted by a simple ion exchange method and the extracts then tested by radioimmunoassay. The mean normal concentration was 1.35 ± 0.29 ng/ml.

Later, direct measurements in serum samples were performed after partial inhibition of T3 binding to TBG by merthiolate and high pH buffer. After correction for the residual non-specific binding a mean normal plasma level of 1.2 ± 0.3 ng/ml was obtained.
STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY
Authors: Søvik Oddmund , Oseid Svein
Published: December 2008

The biological activity of plasma insulin from 4 cases of congenital generalized lipodystrophy has been studied, using rat diaphragm and epididymal adipose tissue in vivo. The results are compared with previous data on plasma immunoreactive insulin obtained in these patients.

2 of the 4 cases exhibited unusually high biological insulin activities during the fasting state as well as after an intravenous (iv) glucose load. In the fat pad assay activities as high as 10 000 μU insulin per ml were observed.

During childhood the biological insulin activities were generally high, although there were large individual variations. However, in the one case studied after the age of puberty, the insulin response to a glucose load was negligible.

Taken together, the biological and immunological activities observed strongly suggest the presence of pancreatic insulin in these patients. It appears that the circulating insulin has a fully biological activity. The decreasing insulin activities after cessation of growth are in agreement with the appearance of frank diabetes at this time.
ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN
Authors: Widström A. , Cerasi E.
Published: December 2008

The initial as well as the late plasma insulin responses to low and high dose glucose infusions were enhanced by iv administration of tolbutamide in eight normal subjects. When expressed as change of the dose-response relationship between blood glucose level and plasma insulin response, the effect of tolbutamide consisted of a shift to the left of the dose-response curve, without increasing the maximum insulin response. This indicates that the drug acts as a sensitizer of the pancreas to the insulinogenic effect of glucose. In this respect, the effect of tolbutamide was of a similar nature both with regard to the initial and late insulin responses. The administration of tolbutamide at the beginning or towards the end of the one hour glucose infusion resulted in comparable enhancements of the late insulin response. Therefore, the effect of tolbutamide on the pancreas seems to be instantaneous, and does not change with prolonged exposure to the drug. Adrenaline, in a moderate dose, inhibited the synergism between glucose and tolbutamide. Since adrenaline in this dose probably does not interfere with glucose metabolism in the β-cell, it is concluded that tolbutamide does not act by modifying the metabolism of glucose, but rather by enhancing its direct insulinogenic signal in the β-cell.
ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN
Authors: Widström A. , Cerasi E.
Published: December 2008

Previous studies in normal man suggest that tolbutamide exerts its insulinogenic effect by modulating glucose-induced insulin release. This is probably achieved by increasing the sensitivity of the β-cells to the action of glucose in eliciting an insulinogenic signal, rather than by influencing the glucose metabolism of the islets. The present paper reports on studies on the relation of tolbutamide to the cyclic AMP system of the islets. Aminophylline, which decreases the breakdown of cyclic AMP, was without effect on tolbutamide-induced insulin release. This indicates that tolbutamide probably does not act by stimulating adenyl cyclase. In contrast, the insulin response to glucagon, an agent known to stimulate adenyl cyclase, was markedly potentiated by tolbutamide. Tolbutamide. in this respect, also showed synergism with arginine, which probably acts by enhancing the formation of cyclic AMP. It is therefore concluded that tolbutamide may influence insulin release by acting as a phosphodiesterase inhibitor or as a potentiator of the action of cyclic AMP on the release mechanisms. The possible relationship of the tolbutamide action with the postulated insulinogenic signal of glucose in the β-cell is discussed.
BIOSYNTHESIS OF 11β-HYDROXYANDROSTENEDIONE BY HUMAN AND BABOON ADRENALS
Authors: Axelrod Leonard R. , Kraemer Duane C. , Burdett James , Goldzieher Joseph W.
Published: December 2008

The conversion of androstenedione and cortisol to 11β-hydroxyandrostenedione was studied by in vitro incubations of human and baboon adrenals and by in vivo perfusion of baboon adrenals. By both approaches, androstenedione appeared to be the major precursor. Some sidechain cleavage of cortisol also occurs during incubation with whole blood.
IMMUNOHISTOCHEMICAL STUDY OF THE HUMAN PITUITARY WITH ANTI-LUTEINIZING HORMONE, ANTI-FOLLICLE STIMULATING HORMONE AND ANTI-THYROTROPHIN SERA
Authors: Robyn C. , Leleux P. , Vanhaelst L. , Golstein J. , Herlant M. , Pasteels J. L.
Published: December 2008

Sections of fixed human pituitaries were investigated by an indirect immunofluorescence technique using antisera obtained following immunization of rabbits with human chorionic gonadotrophin (HCG), human hypophyseal gonadotrophins (HHG) and bovine hypophyseal thyrotrophin (BTSH) preparations. After microphotography of immunofluorescent positive cells, the tissue sections were stained by the Alcian blue (or Thionine aldehyde)-Periodic Acid Schiff-Orange G method. The microscopical fields which had been examined in immunofluorescence were then relocated and photographed again. A correlation was established between the cells reacting with an antiserum and the cell types of the morphological nomenclatures for human adenohypophysis proposed by Romeis (1940) and by Pearse & van Noorden (1963) and those of the functional classification proposed by Herlant & Pasteels (1967).

The specificity of the antisera was checked by immunoelectrophoresis and by neutralization of the biological activities of luteinizing hormone (LH), follicle stimulating hormone (FSH) and BTSH. After selective absorption of the FSH neutralizing antibodies an anti-HCG serum became specific for LH. After selective absorption of the LH neutralizing antibodies an anti-HHG serum was found specific for FSH. The anti-BTSH sera neutralized the biological activity of human TSH, but cross reacted in immunoelectrophoresis with ovine LH and in immunofluorescence with the gonadotrophic cells of human pituitaries. After absorption with HCG, an anti-BTSH serum produced a specific immunofluorescence in large purple blue to dark blue Romeis δ cells filled with fine Alcian blue (or Thionine aldehyde) positive granules. This cell type is equivalent to the S2 mucoids of Pearse or to the "Thyrotrophs" of Herlant. The anti-LH and anti-FSH sera cross-reacted with TSH. Indeed, the S2 mucoids were also fluorescence positive with both anti-gonadotrophic sera. In addition, both anti-LH and anti-FSH sera produced a specific immunofluorescence in the group of purple coloured Romeis δ cells closely related to the S1 mucoids of Pearse. This would indicate that the same cell type contains immunoreactive LH and FSH, which is in contradiction with the description of two different gonadotrophic cell types based on histochemical stainings of human and animal pituitaries obtained in various physiopathological conditions.
THYROXINE STIMULATION OF AMINO ACID INCORPORATION INTO MITOCHONDRIAL PROTEIN: DIFFERENCES BETWEEN IN VIVO AND IN VITRO EFFECTS
Authors: Gordon Amirav , Surks Martin I. , Oppenheimer Jack H.
Published: December 2008

The in vivo and in vitro stimulation of rat hepatic mitochondrial protein synthesis by thyroxine (T4) was compared. In confirmation of Buchanan & Tapley (1966). T4 added to isolated mitochondria rapidly stimulated [14C] leucine incorporation into mitochondrial protein. The in vitro stimulation was reversed after T4 was removed by incubating the mitochondria with bovine serum albumin (BSA). The decrease in T4 stimulation of protein synthesis appeared proportional to the T4 removed by BSA. Thus, it appears probable that exchangeable T4 controls the in vitro system. In contrast, the increase in mitochondrial protein synthesis which was observed 3 to 4 days after pretreatment of hypothyroid rats with labelled and non-radioactive T4 was not reversed by BSA treatment. Moreover, mitochondrial radioactivity could not be extracted with albumin. The in vivo phenomenon does not, therefore, appear to be related to exchangeable hormone in the mitochondria. Furthermore, the estimated quantity of T4 associated with mitochondria after in vivo stimulation was at least two orders of magnitude less than that required to produce comparable stimulation of mitochondrial protein synthesis in vitro. These findings strongly suggest that in vitro and in vivo stimulation of amino acid incorporation by T4 may be mediated by different biochemical mechanisms.
CORTICOTROPHIN-RELEASING FACTOR ACTIVITY IN HYPOTHALAMIC EXTRACTS OF MAN
Authors: Schilling R. M. , Blobel R.
Published: December 2008

Hypothalamic extracts of human corpses of both sexes were tested for corticotrophin-releasing activity using rats which were hypothalamus-blocked with chlorpromazine, morphine, and Nembutal. The released ACTH was determined by fluorometric measurement of the increase of plasma corticosterone. Fractions 2 and 4 (Sephadex G-25 chromatography) showed corticotrophin-releasing activity, whereas fraction 3 which had gonadotrophin-releasing activity in former studies, showed none. In hypophysectomized rats, fractions 2 and 4 showed no ACTH-contamination and contained activity definitely different from vasopressin. Fraction 4 showed a linear log dose-response between 0.05 and 1.25 hypothalamic equivalents. It is concluded that these fractions are identical to CRF and can be well separated from the gonadotrophin-releasing factors.
THYROID PROTEINS AND HORMONE SYNTHESIS IN VARIOUS BENIGN THYROID DISEASES: IN VIVO AND ORGAN CULTURE STUDIES
Authors: Thomas-Morvan Colette , Nataf Berthe M. , Tubiana Maurice
Published: December 2008

The iodoproteins were extracted from 61 thyroid glands with signs of various benign diseases. In 59, the solubility properties and ultracentrifugation behaviour of the iodoproteins were normal, although the hormone synthesis was deficient. The incorporation of radioiodine into the hormones (T4* and T3) was smallest when the iodination of thyroglobulin (Tg) was lowest. In these cases the concentration of Tg was less than normal, but is seemed that the disorders of hormone synthesis were correlated with a deficiency in the iodination of Tg.

Two goitres were clearly different from the other cases studied; thus anomalies of the iodoproteins are rare. In these two goitres, Tg was virtually absent, although thyroid hormones were synthesized. Electrophoresis on acrylamide gel in one of these goitres showed 3 protein bands corresponding to the light fractions in extracts of normal thyroid tissue. Albumin (F1) was the only iodinated protein of this goitre and seemed to support hormone synthesis. Albumin did not appear to be synthesized by the thyroid tissue since 14C-amino acids were not incorporated into this fraction in organ culture. The other fractions (F2 and F3) did not incorporate radioiodine but appeared to incorporate 14C-amino acids to a slight extent. It is possible that this goitre is able to synthesize the precursors of Tg but not Tg itself.
A CASE OF ADRENOCORTICAL HYPERFUNCTION NORMALIZED DURING THE SECOND AND THIRD TRIMESTERS OF THREE PREGNANCIES
Authors: Jørgensen P. I. , Sele V.
Published: December 2008

Detailed hormonal studies were performed before, during and after three pregnancies in an untreated patient with adrenocortical hyperfunction due to hyperplasia.

The patient was clinically characterized by oligomenorrhoea and moderate hirsutism, but showed no signs of virilization or of Cushing's disease. In the non-pregnant state her 17-ketosteroid excretion was elevated to twice the normal value, the androsterone fraction being moderately and the aetiocholanolone fraction greatly elevated, whereas the excretion of dehydroepiandrosterone was essentially normal. In the non-pregnant state the excretion of 17-ketogenic steroids, tetrahydrocortisol, tetrahydrocortisone, cortisone and tetrahydrocorticosterone was also considerably elevated. On high doses of dexamethasone (8 mg daily) or cortisone (100 mg daily) all fractions of 17-ketosteroids as well as the cortisol metabolites were suppressed to about one-half.

Without preceding or simultaneous steroid treatment the patient conceived three times. During all three pregnancies every sign of excessive hormone production ceased. The excretion of 17-ketosteroids in all fractions fell to 20–30%, that of 17-ketogenic steroids to between 30% and 35 %, and that of cortisol metabolites to between 5 % and 46 % of the levels found before and after the pregnancies.

The considerable endocrine activity of the foeto-placental unit may have "normalized" the maternal hypothalamic-pituitary-adrenocortical feed-back mechanism, either by suppressing or by altering the sensitivity of the feed-back system. An alternative theory might be an accelerated rate of cortisol metabolism by the liver in the non-pregnant state which is normalized during the last two trimesters of the pregnancies. The findings are being published as a contribution to the elucidation of the endocrinology of pregnancy.
HYPOTHALAMIC-PITUITARY-ADRENAL FUNCTION IN PATIENTS WITH PITUITARY TUMOURS
Authors: Faglia G. , Ambrosi B. , Beck-Peccoz P. , Travaglini P.
Published: December 2008

Hypothalamic-pituitary-adrenal function was investigated in 43 patients with pituitary tumours (22 acromegalics and 21 chromophobe adenomas) and in 7 patients with craniopharyngiomas. The subjects were divided into two groups, according to the intrasellar or to the suprasellar spread of the tumour. Plasma and urinary 17-OHCS were evaluated in basal conditions and after the following tests: ACTH, metyrapone, dexamethasone, LVP, hypoglycaemia and pyrogen.

Only in 10 subjects were all the tests normal, while there was a complete lack of response to the performed tests in 12 cases.

Under basal conditions a reduced urinary 17-OHCS excretion was observed in 24% of the patients, while plasma 17-OHCS levels appeared to be decreased only in 10 % of patients.

The adrenal reserve was reduced in 4 % of the cases. A greater frequency of negative responses (40 %) was shown by the metyrapone test. Dexamethasone administration failed to suppress plasma 17-OHCS in 29 % of the subjects. The LVP test demonstrated abnormal results in 42 % of the patients examined.

The hypoglycaemia test caused the greatest percentage of impaired responses (58 %) and the pyrogen test gave a higher incidence of normal results.

Our data suggest that the incidence of impaired tests is greater in patients with pituitary tumours with suprasellar spread which particularly tend to cause hypothalamic damage.
EFFECT OF SYNTHETIC THYROTROPHIN-RELEASING FACTOR ON PITUITARY TSH SECRETION IN NORMAL SUBJECTS AND PATIENTS WITH HYPOTHALAMIC-PITUITARY DISORDERS
Authors: Otsuki Makoto , Mori Hidetaro , Baba Shigeaki , Hiroshige Naohisa
Published: December 2008

Different doses of thyrotrophin-releasing factor (TRF) were administered by three different routes (intravenous, subcutaneous and oral) to 87 normal subjects in order to standardize the "TRF test" for the pituitary TSH reserve. The results were: 1) Intravenous single injection may be suitable as a routine TRF test because of the stability of TSH response to TRF and the reliability of TRF administration. 2) The maximum TSH increases were dose-related between 50 and 400 μg, so that we can recommend the use of 50 μg of TRF as a screening test for TSH secretion. 3) Oral administration and slow intravenous infusion of TRF with estimation of thyroxine levels can be useful as an indirect test of pituitary TSH reserve when TSH assays are not available. According to these results, the TRF test was performed in patients with hypothalamic-pituitary disorders. A normal increase in plasma TSH occurred in 10 out of 20 patients with operated pituitary chromophobe adenoma following the administration of 50 or 100 μg of TRF. Two patients showed no rise in plasma TSH after receiving 50 or 100 μg of TRF but a normal rise after receiving 400 or 600 μg of TRF. Little or no rise in the plasma TSH levels occurred following the administration of 100 μg TRF in pituitary chromophobe adenoma and Sheehan's syndrome who had a long standing pituitary insufficiency and secondary hypothyroidism. However, some cases with craniopharyngioma and pinealoma, accompanied with a low level of thyroid function, showed a normal TSH responses to 50 μg of TRF. Since the pituitary of these cases remained intact from tumour invasion, they should be assumed to have tertiary (hypothalamic) hypothyroidism. Of particular interest is the fact that the patients with suprahypophyseal tumour surprisingly showed a supernormal TSH response to 50 μg of TRF.
PLASMA INSULIN AND GROWTH HORMONE IN DAIRY COWS; DIURNAL VARIATION AND RELATION TO FOOD INTAKE AND PLASMA SUGAR AND ACETOACETATE LEVELS
Authors: Hove Knut , Blom Anne Kristine
Published: December 2008

Marked diurnal variations were found in plasma growth hormone (GH), insulin, acetoacetate (AcAc) and sugar in two herds (U and A) of dairy cows kept at two different levels of feeding. Seven animals from each herd were tested. The main diurnal variations were related to food intake, a significant increase in plasma insulin, and a significant decrease in plasma sugar being found. The acetoacetate level rose significantly during feeding in herd U (moderately underfed), while no significant increase was found in herd A (adequately fed). Plasma growth hormone was found to decrease (P < 0.01) only during feeding in herd U, while no change in the GH level could be detected in herd A. The mean level of GH in herd U was found to be twice the value found in herd A. There were no significant differences between the herds in plasma insulin and sugar.

Significant differences in plasma levels of GH, insulin and sugar were found between animals when analysed within the herds. Variations in the levels of insulin and acetoacetate were very small during the night. This is contrary to GH, which shows the least variation during food intake. The correlation coefficient between the plasma components was low, although in many cases significant.
SPECIFIC RADIOIMMUNOLOGICAL DETERMINATION WITHOUT CHROMATOGRAPHY OF PLASMA OESTRADIOL IN MALES
Authors: Doerr P. , Goebel R. , Kuss E.
Published: December 2008

A hapten-radioimmunoassay of plasma oestradiol consisting of an extraction procedure and a final assay using a highly specific antiserum to oestradiol (obtained by immunization of rabbits with oestradiol-6-carboxymethoxime-BSA) was compaired with a similar procedure including a TLC step the specificity of which and other reliability criteria were already established. The plasma oestradiol from 24 normal adult males analysed by both methods showed a fairly close agreement (y = 0.97 x). Pooled normal male plasma analysed in the same way did not reveal any difference: 20.5 ± 0.34 vs. 20.5 ± 0.44 (x̄ ± sem reference method vs. method without TLC). The between-assay-precision of the method without TLC was 10.9% (C. V.), the mean blank 0.8 pg, the sensitivity in terms of 99 % confidence limit of the reagent blank 7.8 pg and the overall tracer recovery 73 %.
IN VITRO STEROL AND STEROID SYNTHESIS BY OVARIES OF HYPOPHYSECTOMIZED IMMATURE RATS TREATED WITH HUMAN GONADOTROPHINS
Authors: Bai R. Uma , Bischoff K. , Macome J. C. , Diczfalusy E.
Published: December 2008

The in vitro conversion of sodium [ 1,2- 14C] acetate into sterols and steroids was studied following the incubation of groups of ovaries from hypophysectomized immature rats with human gonadotrophins. Tritium labelled internal standards were used to monitor procedural losses and sterols and steroids were isolated in a radiochemically homogeneous form. The gonadotrophin preparations studied included a highly purified human urinary LH preparation (with no detectable FSH activity) as well as human urinary FSH and HCG preparations in which the LH and FSH-like activity, respectively, was selectively neutralized by the addition of appropriate antigonadotrophic sera.

The ovaries of saline-treated control animals converted considerable quantities of labelled acetate into cholesterol and small amounts into cholesterol esters. Little, if any, acetate was converted by these ovaries into steroids.

The injection of a human urinary LH-free FSH preparation or of a highly purified human urinary LH preparation resulted in a marked increase in the incorporation of labelled acetate into cholesterol, which was accompanied by a slightly increased incorporation into cholesteryl esters. Small amounts of carbon-14 labelled androstenedione and testosterone were also isolated but no pregnenolone or progesterone was found.
MALE HERMAPHRODITE WITH 46,XX CHROMOSOME CONSTITUTION
Authors: Takayasu Hisao , Kinoshita Kenji , Isurugi Koichiro , Matsumoto Yutaka , Komine Yukikuni , Tonomura Akira
Published: December 2008

A 25-year-old male hermaphrodite with the sex chromosome constitution of 46,XX is reported. Clinical, endocrinological, pathological and cytogenetical studies are presented and discussed in comparison with findings in the so-called XX males reported in the literature.

Some theories to explain the paradoxical occurrence of a testis in XX males and XX male hermaphrodites are mentioned and a possible aetiological relationship between these XX male syndromes and Klinefelter's syndrome is suggested.
STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY
Authors: Oseid Svein
Published: December 2008

Studies of the plasma immunoreactive human growth hormone (HGH) levels in six patients with congenital generalized lipodystrophy revealed low normal basal values without any rise in plasma HGH following stimulation with insulin-induced hypoglycaemia, arginine or vasopressin. The results are interpreted as indicating either a disturbed regulation of the HGH secretion or the formation of an abnormal growth hormone.
EVIDENCE FOR THE INTERNAL FEEDBACK PHENOMENON IN HUMAN SUBJECTS: EFFECTS OF ACTH ON PLASMA CRF
Authors: Upton G. V. , Corbin A. , Mabry C. C. , Hollingsworth D. R.
Published: December 2008

Corticotrophin (ACTH) was administered to three patients with lipoatrophic diabetes (LD), one hypophysectomized LD patient and one control subject in an effort to simulate the internal feedback mechanism as measured by plasma corticotrophin releasing factor (CRF) activity. Plasma cortisol was determined at zero, five and eight hours after the beginning of ACTH infusion. Every LD patient showed a lack of adrenal response to ACTH as evidenced by the absence of significant increments in plasma cortisol levels. The control subject had a normal adrenal response to ACTH. Three of the four LD patients showed a reduction in plasma CRF levels after ACTH. The control subject had no detectable plasma CRF before or after ACTH.

The reduction in plasma CRF accompanied by constant levels of plasma cortisol after ACTH administration suggests a direct regulatory effect of ACTH on CRF secretion. These data provide strong supportive evidence for the existence of an internal or 'short-loop' feedback system in human subjects in which the levels of plasma CRF appear to be regulated directly by blood levels of ACTH – presumably at the hypothalamic level.