bluuebunny/crossref_metadata_2025 huggingface dataset:
IN VITRO STUDIES OF THE RELEASE MECHANISM FOR VASOPRESSIN IN RATS
Authors: Thorn N. A.
Published: December 2008

A study was made of the release of vasopressin activity from groups of isolated posterior pituitary hemilobes of rats, incubated in media with different ionic compositions and with different drugs added to the medium.

Nicotine, amyl nitrite and ATP, which have been reported to cause a large in vivo release of hormone had no significant releasing effect in vitro. Caffeine too did not cause any release of hormone activity.

About 5% of the vasopressin activity extractable from the isolated posterior pituitary hemilobes was released during stimulation with a high concentration of potassium in the medium. No more than this percentage could be mobilized during such a stimulation, even after further subdivision of the posterior pituitary glands, prolongation of the stimulation period or after increasing the calcium concentration in the medium five-fold.

No release into the medium of vasopressin binding protein could be demonstrated during stimulation of vasopressin release.

The results seem to be in agreement with the hypothesis that the release of vasopressin is intimately associated with arrival of impulses to the nerve endings in the posterior pituitary gland and that it takes place from a small pool of readily available hormone, presumably by dissociation of the hormone from the carrier protein.
PURIFICATION AND SEPARATION OF FOLLICLE STIMULATING HORMONE (FSH) AND LUTEINIZING HORMONE (LH) FROM HUMAN MENOPAUSAL GONADOTROPHIN (HMG)
Authors: Eshkol Aliza , Lunenfeld B.
Published: December 2008

Effects of a biologically apparently pure human urinary FSH preparation on the ovaries and uteri of intact infantile mice are described. This study indicates that such an FSH preparation stimulates follicular development and ovarian weight increase. Despite significant ovarian stimulation, the uteri of animals so treated remain infantile.
MAINTENANCE BY OESTRONE AND PROGESTERONE OF DECIDUOMAL GROWTH IN RATS GIVEN METHALLIBURE (I. C. I. 33,828)
Authors: Harper M. J. K.
Published: December 2008

Deciduomal growth was stimulated in rats by inserting a silk thread into the lumen of one uterine horn on day 5 of pseudopregnancy. The degree of response was evaluated at autopsy on day 9. Deciduomal growth under such conditions was found to be reduced by the administration of methallibure (I. C. I. 33,828), 100 mg/kg p. o., on days 2 to 4 or – to a lesser extent – on days 4 to 6. Additional treatments with oestrone, 1 μg/rat and/or progesterone, 2 mg/rat, given subcutaneously on various days during and after administration of methallibure on days 2 to 4, failed to restore deciduomal growth to normal levels. This was achieved, however, when methallibure was given on days 4 to 6, by additional treatment with progesterone on days 4 to 7 combined with oestrone on days 4, 4 and 5, or 4 to 7, although neither progesterone nor oestrone was effective alone.

These results indicate that the administration of methallibure reduces the output of both oestrogen and progesterone from the ovary to levels below those required for normal deciduomal growth. They also suggest that this effect persists for more than 2 days after administration of the compound is stopped.
TAGESPERIODISCHE SCHWANKUNGEN DER URINAUSSCHEIDUNG UND DES ADIURETINGEHALTES IM HYPOPHYSENHINTERLAPPEN MÄNNLICHER WISTAR-RATTEN
Authors: König Annemarie , Meyer A.
Published: December 2008

Adult male Wistar rats were kept at a constant temperature and in an alternating light-dark environment consisting of 12 hours of light with 150 lux (7 a. m. – 7 p. m.) and 12 hours of darkness with 0.1 lux (7 p. m. – 7 a. m.). The urine output was measured at 4-hourly intervals over several 24-hour periods. Diurnal changes with a high excretion at midday and a low excretion at midnight were found. The content of antidiuretic hormone of the posterior pituitary lobe was estimated at 10 a. m., 2 p. m., 6 p. m., and at 10 p. m., 2 a. m., 6 a. m. in the months of March, April and May. The highest amount occurred during darkness with maximal values at 6 a. m., the lowest during light with minimal values at 2 p. m.
SOME OBSERVATIONS ON A SENSITIVE BIOASSAY FOR THYROTROPHIN. APPLICATION TO NORMAL, HYPER- AND HYPOTHYROID HUMAN SERUM
Authors: Desbarats-Schönbaum M. L. , Sellers E. A. , Belzile A. , Schönbaum E.
Published: December 2008

A four-point in vitro bioassay for human serum thyrotrophin (TSH) has been described by Kirkham (1962). In this assay, thyroid tissue of PTU-treated guinea pigs is incubated with 131I-iodide. »Release« of 131I after addition of KCNS is measured. This »release« is inversely proportional to the logarithm of the TSH activity in the incubation medium. We have found that erratic responses occasionally occurring in this assay are due to »non-specific« stimulation. The »non-specific« material affecting 131I release is removed from human serum and other preparations by filtration through »Sephadex G-25 medium«

Rabbit anti-bovine TSH abolishes the bioassay response to bovine TSH and to human serum TSH.

The system does not respond to LATS levels which give a very high response in the McKenzie assay.

It is suggested that the amount of 131I bound in the incubated tissue is directly related to the TSH concentration and that therefore the remainder of the trapped 131I which is free to diffuse out gives an inverse measure of the TSH concentration.
SEPARATION AND QUANTITATIVE DETERMINATION OF 131I-TRIIODOTHYRONINE AND 131I-THYROXINE IN HUMAN PLASMA BY THIN LAYER CHROMATOGRAPHY
Authors: Favino Angelo , Emrich Dieter , von zur Mühlen Alexander
Published: December 2008

A method is described for the quantitative determination of 131I-triiodothyronine and 131I-tetraiodothyronine in human plasma after oral administration of 131I-iodide.

Steps in the method are: acidified n-butanol extraction of the thyroid hormones from the plasma deprived of inorganic iodine by means of an ion exchange resin; addition of stable iodo-aminoacid carriers to the butanol extract and its evaporation to dryness under reduced pressure; bidimensional thin layer chromatography of the rediluted extract on cellulose in combined organic alkaline and organic acid systems; staining of the carriers with eerie sulphate-sodium arsenite reagent and diluted methylene blue; radioactivity measurements of the cellulose scraped from the stained spots in a well type scintillation counter.

The reliability of the method was established by recovery experiments and by duplicate chromatography of plasma to which mixtures of 131I-T3 and 131I-T4 and 131I-iodide were added. Its specificity was confirmed by autoradiography. Good agreement was found with the results yielded by simultaneous paper chromatography of the same extracts. The method requires smaller amounts of plasma and allows quicker determinations than paper chromatographic procedures. Relative determinations of 131I-T3 and 131I-T4 are reported in some euthyroid and hyperthyroid patients given therapeutic and diagnostic doses of 131I-iodide.
THE INSULIN-LIKE ACTION OF PEPSIN AND PEPSINOGEN
Authors: Rieser Peter
Published: December 2008

Alkali-denatured pepsin and pepsinogen, at concentrations corresponding to 0.5 units of insulin per milliliter, act like insulin in the intact rat diaphragm. They stimulate the cellular uptake of 3-0-methyl glucose and promote the synthesis of glycogen from glucose. The insulin-like action of digestive enzzymes is considered to be a consequence of their evolutionary descent from a protein precursor in common with that of insulin. The nature of the cellular response to insulin and insulin-like enzymes may depend on the degree to which these molecules are able to complement a membrane-sited receptor to form an active enzyme.
THE POLYCYSTIC OVARY. VII.
Authors: Goldzieher Joseph W. , Fariss Bruce , Boyd Frankie G.
Published: December 2008

The clinical course of a patient with polycystic ovarian disease was characterized by recurrent endometrial hyperplasia and bleeding which eventually required panhysterectomy. Urinary oestrogens did not fall after castration and secretion rate studies showed oestrone production averaging 16–18 μg/d on one occasion and oestradiol production averaging 72 μg/day during another 4-day interval. There was a marked discrepancy between secretion rate and routine urinary oestrogen measurements. Peripheral aromatization of testosterone was 0.6% and of androstenedione less than 1.2%. An oestradiol production of 72 μg/day is not likely to have been derived exclusively from peripheral aromatization of these androgens, suggesting that direct adrenal secretion of oestrogen may play a role in some cases of polycystic ovarian disease.
EXPERIENCES IN TREATING EXCESSIVE HEIGHT IN GIRLS WITH CYCLIC OESTRADIOL VALERATE.
Authors: Whitelaw M. James
Published: December 2008

Nineteen prepubertal girls ages 8–10 were treated cyclically with oestradiol valerate. They showed a marked generalized anabolic effect. Their linear average growth was 10.8 cm and their average weight gain was 8.73 kg. The bone age advanced a maximum of 44 months in the youngest patient. The average advance at the end of one year was 34 months. There was a marked increase in the size of the breasts.

In the 11 year group of 8 girls after one year of therapy, their height increment was 7.3 cm.

In the pubertal girls, ages 12–16, their growth only averaged 3.4 cm, the average bone age advance was 27.5 months. A total of 27 girls have now reached their full stature.

The best resuls are therefore obtained in preventing excessive height if therapy is initiated between the ages of 8 and 10. The saving becomes progressively less as one approaches a bone age of 15 when it is nil.

The chronic administration of oral oestrogens may cause serious side effects and therefore is to be avoided.
STEROID HORMONE FORMATION BY THE RAT OVARY.
Authors: Rice Bernard F. , Segaloff Albert
Published: December 2008

Ovaries were transplanted to the spleens of spayed female rats. After 18 months, ovarian neoplasms had developed. Slices of two different ovarian tumours were incubated with 100 μc acetate-1-14C. Radioactive steroid hormone formation was assessed quantitatively by the reverse isotope dilution technique. Tissue from one ovarian neoplasm, considered to be a luteoma, formed radioactive progesterone and 20α-hydroxy-pregn-4-en-3-one. The formation of 3β-hydroxy-pregn-5-en-20-one, androst-4-ene-3,17-dione, testosterone, 3β-hydroxy-androst-5-en-17-one, 17-hydroxy-pregn-4-ene-3,20-dione, oestrone and 17β-oestradiol could not be established. No radioactive steroid hormone synthesis could be detected using granulosa cell tumour tissue.
ENDEMIC GOITRE IN PEDREGOSO (Chile)
Authors: Beckers C. , Barzelatto J. , Stevenson C. , Gianetti A. , Pardo A. , Bobadilla E. , De Visscher M.
Published: December 2008

Iodine kinetic studies have been performed in 61 Indians from the Pedregoso goitre endemic in Chile. The daily absolute iodine uptake in the thyroid averaged 98 μg I, with maximal values in the cases of diffuse goitre. The mean thyroxine degradation rate in the same group of patients corresponded to 102 μg I per day, when using the mean thyroxine distribution space and thyroxine (T4) fractional turnover rate obtained from a comparable group of the same population. The output of iodine from the thyroid was calculated by 3 different methods. In each case, the iodine output appears to be higher than the amount of halogen accumulated by the thyroid or metabolized by the tissues.

These findings suggest an important spillage of iodine (as iodide and/or iodinated tyrosines) by the goitrous gland. Such a disturbance apart from nutritional iodine deficiency may be an important factor in the pathogenesis of endemic goiter.
STIMULATION OF ADRENOCORTICOIDOGENESIS BY PRECORTICOTROPHIN AFTER ACTIVATION
Authors: Dasgupta P. R. , Hirai Masanao , Dorfman R. I.
Published: December 2008

Precorticotrophin (precursor of corticotrophin) after acid treatment, enhanced the rate of steroid biosynthesis in the adrenal cortex of hypophysectomized rats. The corticosterone content of both adrenal tissue and the adrenal vein blood were unchanged when the rats were treated with a pig pituitary precorticotrophin preparation. However, after the precorticotrophin preparation was activated by acid treatment, a significantly higher content of corticosterone was found both in the adrenal tissue and in the adrenal venous plasma.
ACTIVITY OF VARIOUS STEROIDS IN INHIBITING SEXUAL DEVELOPMENT IN RATS WHEN INJECTED AT THE AGE OF 5 DAYS
Authors: Kind Fred A. , Dorfman Ralph I.
Published: December 2008

Various ring A phenolic steroids and C-19 neutral compounds injected into 5 day old rats were studied as inhibitors of sexual development. At the age of 45 days oestrogens were active in both sexes while androgens were less active. The activity of oestrogens in this test did not correlate with their oestrogenic potency as measured in the uterotrophic test. Some doses caused precocious vaginal introitus but not inhibition of luteinization.
OESTROGEN ANTAGONISMS: TEMPORAL SEQUENCE OF STEROID BLOCK OF OESTRONE-INDUCED CHANGES IN VAGINAL SMEARS OF MICE
Authors: Edgren Richard A.
Published: December 2008

Oestrone, at a total dose of 2 μg was administered over 4 days to spayed female mice, and vaginal smears were examined twice daily for the next 6–8 days. The proportion of mice showing a positive vaginal response rises through day 2 and 3 to a plateau on days 4 and 5. Putative oestrogen antagonists, progesterone, testosterone propionate, deoxycorticosterone acetate or cortisone were given in single mg injections on day 1, 2, 3 or 4. Cortisone had no effect upon the oestrone-induced response and the effect of DCA was seen only on day 6 when it was administered on day 4. Progesterone on day 1 delays the oestrogen effect; on day 2 it inhibits the mid-portion of the time-response curve, producing a bimodal curve; and on day 3 and 4 hastens the return of the mice to the castrate condition. TP which appears to be slower in onset of action than progesterone, does not affect initial phases of the curve, but tends to hasten return to castrate condition. Oestrone alone was given with various of the days deleted from the design. The patterns of the responses did not correspond to those obtained when progesterone or testosterone were administered, implying that these steroids have direct effects and do not simply negate one or more of the oestrone injections.
SERUM PROTEIN-BOUND IODINE AND SERUM THYROXINE DURING PERPHENAZINE THERAPY
Authors: Mølholm Hansen J. , Siersbæk-Nielsen K.
Published: December 2008

Four out of 19 patients treated with perphenazine who were investigated in 1962, and 5 out of 31 patients who were investigated in 1966 had a raised PBI. The increase was most marked in the patients investigated in 1962. Measurements of dialysable thyroxine revealed that the increase was not due to an increase in thyroxine-binding globulin. All 50 patients had normal serum thyroxine as estimated by Murphy's method. Most probably the increase in PBI was due to the fact that the perphenazine tablets contain an iodine compound, which in some subjects may become bound to the serum proteins.
EFFECT OF POTASSIUM ON ADRENAL ALDOSTERONE PRODUCTION IN RATS
Authors: Sturcz J. , Spät A. , Szöcs G. , Kövér G. , Farkas Á.
Published: December 2008

The infusion of K at a rate of 17 μEq./min for 2 hours to anaesthetized rats resulted in a significant rise in aldosterone production by incubated rat adrenal slices. This change occurred without any significant alteration in the ECG pattern. Since the same dose of K was ineffective when given to nephrectomized rats, it is assumed that the effect of potassium is mediated through the kidneys.

The infusion of 25 μEq./min for 2 hours increased the rate of adrenal aldosterone secretion even in the nephrectomized animals, indicating an extrarenal site of action of potassium ions. The fact, however, that this latter dose was associated with severe ECG changes suggests that this extrarenal mechanism is not involved in the physiological control of aldosterone secretion.
THE PARATHYROIDS IN CORTICOSTEROID-TREATED MALE RATS
Authors: Hansson C. Göran
Published: December 2008

The parathyroid morphology was studied in male rats following the administration of cortisone (1, 3 and 9 mg/day) and DOCA (0.5, 1.5 and 4.5 mg/day). The parathyroid volume and mitotic rate decreased after cortisone treatment, the findings being suggestive of an inhibition of parathyroid function. In the parathyroids of the DOCA-treated rats, there was an increased mitotic rate and an increased number of cells in DNA-synthesis as determined by an autoradiographic study after the administration of tritiated thymidine, indicating an increased activity of the glands. The serum potassium and the renal concentrating capacity, measured as urine osmolality, were significantly lowered and the urinary volume significantly increased in the DOCA-treated rats but these showed no significant changes in total serum calcium and phosphorus. An explanation of the increased parathyroid activity in the DOCA-treated rats might be that DOCA causes hypokalaemic nephropathy and alkalosis with lowering of the plasma ionized calcium level.
AMINOPEPTIDASE ACTIVITY IN FOETAL RAT PARATHYROIDS AND ITS INHIBITION BY VITAMIN D-INDUCED HYPERCALCAEMIA IN THE MOTHER RAT
Authors: Hansson C. Göran , Svalander Christian
Published: December 2008

Previous investigations have suggested that there is a close correlation between the aminopeptidase activity in rat parathyroids and the production and secretion of parathyroid hormone. The present investigation demonstrates that parathyroids of rat foctuses 16, 19 and 22 days old have a high aminopeptidase activity. Vitamin D-induced hypercalcaemia in the mother rat reduces the aminopeptidase activity, parathyroid volume and mitotic rate in the parathyroids of 22 days old rat foetuses. The results of the present investigation support the view that the foetal rat parathyroids function from the 16th day of gestation and that induced hypercalcaemia of the pregnant rat inhibits this function.
THE PLASMA INSULIN RESPONSE TO GLUCOSE INFUSION IN HEALTHY SUBJECTS AND IN DIABETES MELLITUS
Authors: Cerasi Erol , Luft Rolf
Published: December 2008

Plasma insulin concentration was measured during a standardized glucose infusion test (GIT) in 85 healthy subjects with a normal glucose tolerance and in 28 patients with manifest diabetes mellitus or decreased glucose tolerance. Each test was evaluated with the aid of an analogue computer model, and parameters characterizing different parts of the insulin curve during GIT were obtained. Large variations existed in all parameter values both in the normal and diabetic groups, and the overlapping between the two groups was considerable.

In 15 out of 85 healthy subjects the plasma insulin response during GIT was of the diabetic type as judged from the frequency distribution of the computer parameters (low values). The similarity was still more striking when the characteristics of the insulin curves in these 15 subjects were compared with those in patients with mild diabetes or with a decreased glucose tolerance only.

It is postulated that this type of low insulin response reflects a derangement of the release of insulin into the circulation, and that it marks an alteration which probably is a prerequisite for the development of diabetes mellitus. In this sense, these subjects may be considered to be potential diabetics.
THE INFLUENCE OF THE PLASMA INORGANIC IODINE CONCENTRATION ON THYROID FUNCTION IN DEHALOGENASE DEFICIENCY
Authors: Harden R. McG. , Alexander W. D. , Papadopoulos S. , Harrison M. T. , Macfarlane S.
Published: December 2008

Iodine metabolism and thyroid function were studied in a patient with hypothyroidism and goitre due to dehalogenase deficiency. Initially the plasma inorganic iodine (PII) level was within the normal range but circulating levels of hormone were low and the thyroid clearance and absolute uptake of iodine (AIU) by the thyroid were high.

Administration of iodide supplements resulted in a rapid rise in the plasma thyroxine concentration and restoration of the euthyroid state. Thyroid hormone synthesis appeared to proceed normally when the PII exceeded 1.0 μg/100 ml. This was achieved by increasing the intake of iodide by 612 μg per day. At PII levels around 10 μg/100 ml there was evidence of increased levels of circulating thyroid hormone.
EFFECTS OF PROGESTERONE AND PENTOBARBITONE ON HYPOTHALAMIC INDUCTION OF OVULATION IN THE 5-DAY CYCLIC RAT
Authors: Zeilmaker G. H. , Moll J.
Published: December 2008

The involvement of the central nervous system in the inhibitory effects on ovulation of progesterone and pentobarbitone was studied in 5-day cyclic rats. The occurrence of ovulation following electrochemical stimulation of the median eminence or the preoptic area was the main technique used in this work. The following experiments are reported.

Following pretreatment with 10 mg progesterone on day 3 of the cycle stimulation of the preoptic area on day 4 was almost completely ineffective. However, stimulation of the median eminence was effective in most of these progesterone-treated rats (I).

Following pretreatment with the much lower dose of 0.5 mg progesterone, spontaneous ovulation was still suppressed. However, stimulation of the preoptic area was now capable of inducing ovulations in most animals, but only if ether anaesthesia was used during the stimulation procedure. If combined pentobarbitone-ether anaesthesia was used, most animals did not ovulate (II).

In other experiments stimulation of the median eminence or preoptic area was performed on day 3 (dioestrus) under ether anaesthesia or combined pentobarbitone-ether anaesthesia in normally cycling rats, which did not receive progesterone. Under ether anaesthesia preoptic stimulation induced ovulation in most animals, but under combined pentobarbitone-ether anaesthesia none of the animals ovulated (III).

Stimulation in the median eminence under otherwise identical experimental conditions, induced ovulation without exceptions under ether anaesthesia and in half of the cases operated under combined pentobarbitone-ether anaesthesia (IV).

It is concluded that these findings support the concept that the inhibitory effect of progesterone on ovulation is due to an action on the central nervous system. Furthermore, consideration of the possible mechanisms of action of progesterone and of pentobarbitone in inhibiting ovulation led to two alternative hypotheses: the two substances exert their effect on ovulation at the same site, or, pentobarbitone acts at a level closer to the median eminence.
ETUDE DE L'ACTION DU FACTEUR HYPOTHALAMIQUE LRF (LH-RELEASING FACTOR) CHEZ LE RAT IN VIVO & IN VITRO
Authors: Jutisz Marian , Bérault Annette , Novella Marie-Anne , Ribot Geneviève
Published: December 2008

A highly purified ovine LH-releasing factor (LRF) was obtained by a modification of the method previously described. After the fractionation of a crude hypothalamic extract on a Sephadex G-25 column, the LRF fraction was desalted and partially purified by chromatography on a Dowex 50 × 12 column and on an Amberlite CG 4B column. The last step of this method, chromatography on a CMC column, gave a purification of about 1600 times with respect to the crude extract.

The action of this highly purified LRF preparation was studied on rat pituitary glands in vivo and in vitro.

The method used in vivo was the evaluation of the LH-releasing effect of LRF in chronically ovariectomized, steroid-blocked rats (Ramirez & McCann 1963 b). A procedure was developed which allows a 4-fold concentration of the plasma LH from these rats, so that it can be assayed by a 4-point assay method.

In the in vitro method, the pituitary glands of ovariectomized steroidblocked rats (Schally & Bowers 1964 a) were incubated in a Krebs-Ringer buffer with or without LRF, and the LH released into the medium was assayed using the O.A. A.D. method of Parlow. A dose-response curve was established between the log doses of LRF and the amount of LH released. This method can be used as a sensitive and specific assay for LRF.

It was shown that a dose of 1.22 μg of LRF releases approximately 5 μg of LH per mg of pituitary tissue. This is about double of the amount of this hormone originally present in the pituitary glands of these rats (2.7 μg/mg). This leads us to the conclusion that the excess of this hormone was probably synthetized during the process of incubation. The amount of steroids injected as a blocking agents, appears to be very important for both in vivo and in vitro tests.
SERUM CONCENTRATION OF α2-MACROGLOBULIN, HAPTOGLOBIN AND α1-ANTITRYPSIN IN DIABETES MELLITUS
Authors: Ganrot P. O. , Gydell K. , Ekelund H.
Published: December 2008

The serum concentration of α2-macroglobulin and that of haptoglobin, the two main components of the electrophoretic α2fraction, and of α1-antitrypsin were studied in a series of outpatients with diabetes mellitus. In all age groups a significant increase of α2-macroglobulin was noted. In adults the increase showed a significant positive correlation with the duration of the disease and was accentuated in the presence of nephropathy with proteinuria. No further increase was noted in the occurrence of other vascular complications. In adult diabetics haptoglobin and α1-antitrypsin were significantly increased. No correlation was found between the duration of the disease and the concentration of haptoglobin or α1-antitrypsin. Neither haptoglobin nor α1-antitrypsin were increased in diabetic children. It is proposed that the concentration of α2-macroglobulin is more related to diabetes mellitus per se than that of haptoglobin or α1-antitrypsin, which are increased most in response to complications with inflammatory reaction.
DIE ENDEMISCHE STRUMA IN TIROL.
Authors: Riccabona G.
Published: December 2008

Five villages in the Tyrol – a well known endemic goitre area – were examined. To study the pathogenesis of the disease iodine determinations were made in drinking water and 24 hour urines, the PBI was recorded and thyroid iodine metabolism was followed using 125I as tracer. The sera of the examined patients were checked for thyroid autoantibodies and careful family histories were taken.

The results showed that the Tyrol is an iodine deficient country with a still severe goitre endemic. Iodine deficiency is therefore certainly involved in the pathogenesis of goitres in this area. As there were, however, obviously iodine deficient persons without goitre in the same living conditions and as genetic factors are shown to be important also, an effort was made to clarify the complex pathogenesis of the disease using radiochromatography. However, no block in thyroid hormone synthesis could be demonstrated.
ENZYMATISCH-FLUOROMETRISCHE BESTIMMUNG DER CORTISOLBINDUNGSKAPAZITÄT DES PLASMA
Authors: Leybold K. , Rieper J. , Weissbecker L.
Published: December 2008

A simple method for the determination of cortisol-binding capacity is described. For saturation of the cortisol-binding proteins, plasma samples are incubated with an excess of cortisol. In the next step NADPH and liver microsomes of female rats are added. The microsomal Δ4-3-ketosteroid hydrogenase only reduces non protein-bound cortisol to tetrahydrocortisol-5α. Then the steroids are extracted by dichloromethane, and after some purification steps analyzed by fluorometry. Tetrahydrocortisol gives practically no fluorescence. The cortisol determined by this method corresponds to protein-bound cortisol and indicates the extent of cortisolbinding capacity. Precision and accuracy of the method were found to be good.

The values of cortisol-binding capacity obtained by our method are compared with the results of other authors. The mean value of adult men was 25.5 ± 3.4 μg/100 ml, that of pregnant women, mens IX-X, 42.3 ± 4.2 μg/100 ml.
THE OCCURRENCE OF ABNORMAL INSULIN AND GROWTH HORMONE (HGH) RESPONSES TO SUSTAINED HYPERCLYCAEMIA IN A DISEASE WITH SEX CHROMOSOME ABERRATIONS (TURNER'S SYNDROME)
Authors: Lindsten J. , Cerasi E. , Luft R. , Hultquist G.
Published: December 2008

The plasma insulin response to prolonged glucose infusion was studied in 14 patients with Turner's syndrome having a normal intravenous glucose tolerance test. The insulin response was in most instances delayed and diminished in spite of a higher than normal blood glucose level.

The fasting plasma growth hormone (HGH) level was elevated, and hyperglycaemia induced a paradoxical increase in plasma HGH in most of the patients. The HGH response to hypoglycaemia was normal.

Oestrogen replacement accentuated the paradoxical HGH reaction to hyperglycaemia while the insulin response diminished further.

In contrast to earlier studies no increase in the frequency of diabetes was found among the relatives of the Turner patients.

In one subject there was a definite hyperplasia of the islet tissue of the pancreas with signs of decreased activity of the β-cells, in a second one the amount of islet tissue was fairly high.

Possible relationships between the above findings are discussed.
URINARY EXCRETION OF TESTOSTERONE AND EPITESTOSTERONE IN HIRSUTISM
Authors: France J. T. , Knox B. S.
Published: December 2008

The urinary excretion of testosterone and epitestosterone has been studied in 11 normal and 31 hirsute subjects. The mean testosterone excretion (μg/24 hours) in normal males was 67.3 (range 36.8–133.2), in normal females 11.2 (range 4.5–16.0), in hirsute females with regular menses 20.7 (range 2.5-82.5), in hirsute females with irregular menses 34.6 (range 17.1-92.8), and in hirsute females with virilization 56.7 (range 26.8–98.5). The mean epitestosterone excretion (μg/24 hours) in normal males was 28.1 (range 18.5–47.4), in normal females 8.0 (range 5.9–10.9), in hirsute females with regular menses 15.6 (range 5.1–34.7), in hirsute females with irregular menses 23.0 (range 9.9–37.8) and in hirsute females with virilization 26.7 (range 12.0–45.9). In most cases of hirsutism there was a raised urinary excretion of testosterone and epitestosterone, the exception being a small number of hirsute women with regular menses. Epitestosterone excretion unlike that of testosterone showed no correlation with virilization
THE MECHANISM IN INHIBITION OF OVULATION IN ORAL CONTRACEPTION. III.
Authors: Starup J. , Lebech P. E.
Published: December 2008

Six normally menstruating women aged 21 to 28 were studied for 3 cycles, viz. one control cycle followed by two cycles in which they were treated from day 5 to day 24 with daily dose of 5 mg of 6-methyl-6-dehydro-17α-acetoxyprogesterone (megestrol acetate) + 0.1 mg of 17α-ethynyl-oestradiol-3-methylether (mestranol). In all 3 cycles the daily excretion of total pituitary gonadotrophins and luteinizing hormone (LH) was determined from day 8 to day 21. In addition, the excretion of pregnanediol was determined on days 7 and 22 in every cycle, and the basal body temperature was recorded daily for the entire period.

In the control cycle 4 out of the 6 patients showed a definite mid-cycle peak in the excretion of total gonadotrophins, whilst a definite mid-cycle peak in the excretion of LH was found in 4 patients and a more questionable peak of LH in the remaining 2 patients. All 6 patients showed typical biphasic temperature curves and the excretion of pregnanediol on day 22 indicated normal ovulatory cycles.

In the first treatment-cycle, 5 out of the 6 patients already showed no mid-cycle peak in the excretion of total gonadotrophins. The last patient had only a small questionable peak. A similar pattern was seen in the excretion of LH. All the 4 patients who had a definite mid-cycle peak of LH in the control cycle now showed a complete disappearance of this peak, while the remaining 2 patients showed only a questionable peak. In the second treatment-cycle none of the 6 patients showed a mid-cycle peak in the excretion of total gonadotrophins, and only 2 out of the 6 patients had a questionable peak in the excretion of LH. Furthermore, in all treatment-cycles the excretion of pregnanediol was less than 0.8 mg/day on day 22.

Thus the present investigation indicates that the combination of megestrol acetate and mestranol inhibits ovulation and suppresses the synthesis and/or the release of LH.
EINFLUSS VON CYCLUS UND EXOGENER HORMONZUFUHR AUF STOFFWECHSELVORGÄNGE DES RATTENUTERUS
Authors: Schmidt H. , Noack I. , Walther H. , Voigt K. D.
Published: December 2008

The first significant increase of weight, RNA and protein was observed in the uterus of spayed rats twelve hours after the intraperitoneal administration of a single dose of 1 μg oestradiol. There was no significant increase of DNA. At the same time the activities of glucose-6-phosphate dehydrogenase, fructose-1,6-diphosphate aldolase, isocitrate dehydrogenase and leucine aminopeptidase had increased significantly. Twentyfour hours after the injection the augmented values began to decline. Three injections of 1 μg oestradiol, given at 24 hour intervals obtained similar changes, the only difference being that these changes were more marked and that a DNA increase was also observed. The augmentation of protein, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and fructose-1,6-diphosphate aldolase content of cells induced by repeated oestradiol injections was inhibited partly by 1 mg progesterone when administered together with the last dose of oestradiol. During the normal oestrus cycle of the rat uterus an increase of uterine weight, DNA and RNA content and also of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and 1,6-diphosphate aldolase activities was observed, whereas isocitrate dehydrogenase, malate dehydrogenase and leucine aminopeptidase did not change significantly. It would appear that the changes after exogenous hormone administration reflect those of the normal cycle as regards both their extent and timing. The importance of these findings in connection with hormone-induced pathways of uterine metabolism is discussed.
THE POLYCYSTIC OVARY. VIII.
Authors: Axelrod Leonard R. , Goldzieher Joseph W.
Published: December 2008

Tissue from one normal (cycle day 10) and 5 polycystic ovaries was incubated with radioactive pregnenolone, progesterone, testosterone, androstenedione or oestrone, and the metabolites isolated in radiochemically pure form. The patterns of pregnenolone metabolites with polycystic tissue differed from one another and from that of normal ovarian mince. Conversion of the substrate was generally much greater with the former, and in one instance the cortical portion was much more active than the medulla. 3β-ol dehydrogenase activity was markedly decreased in one case. 19-Oxygenation was seen infrequently and no aromatization was observed. On the other hand, 16-hydroxylation and 20-reduction were occasionally very prominent. Incubation of normal tissue with C19 precursors yielded oestrogen whereas polycystic tissue did not. The pathways androstenedione→testosterone→oestradiol and testosterone→16-hydroxy-testosterone→oestriol are suggested by the metabolites of the normal tissue. Under the experimental conditions, the reduction of oestrone to oestradiol was much more prominent than the reduction of androstenedione to testosterone by the polycystic tissue.
THE EFFECT OF METYRAPONE ON ALDOSTERONE SECRETION IN MAN
Authors: Tucci Joseph R. , Espiner Eric A. , Jagger Paul I. , Lauler David P.
Published: December 2008

The influence of metyrapone (SU4885; 2-methyl-1,2, bis-[3-pyridyl]-1-propanone), an adrenocortical blocking agent, upon aldosterone secretion was evaluated in nine normal subjects and in seven patients including four with Cushing's syndrome, two with primary aldosteronism and one with hypopituitarism. Following equilibration on a constant diet restricted in sodium, metyrapone was given orally in a dose of 750 mg at four hourly intervals for two consecutive days. Aldosterone secretion rates were measured on the day prior to and on the second day of metyrapone administration. Despite the stimulus of salt deprivation, metyrapone was uniformly effective in reducing aldosterone secretion rates in all subjects. Concomitant ACTH stimulation in one normal subject failed to overcome the metyrapone induced block. In the majority of subjects, metyrapone administration was associated with a mild natriuresis.
BEGRENZT DIE KAPAZITÄT DER 17β-STEROID-DEHYDROGENASE DEN IN VIVO UMSATZ VON OESTRADIOL ZU OESTRON?
Authors: Wenzel Marlin , Kraas Ernst
Published: December 2008

By injecting oestradiol-17α-T and testosterone-17α-T to animals or men and measuring the specific activity of tritium in the body water, it is possible to determine the oxydation of these steroids to the corresponding ketones in the whole organism. Using this method combined with a simple arrangement for collecting breathing water it can be shown that the capacity of the 17β-steroid-dehydrogenase does not limit the oxydation of oestradiol and testosterone in intact rats and that no significant difference in the oxydation of both steroids can be found between 0.2 μmol/kg – 200 μmol/kg of injection dosis.
LIGHT AND ELECTRON MICROSCOPICAL STUDY OF THE EFFECT OF OESTROGEN ON THE CHICKEN OVIDUCT
Authors: Ljungkvist H. I.
Published: December 2008

Oviducts from 20 one-day old chickens were used. Ten chickens were injected subcutaneously with 0.2 mg oestradiol for 5 days, the remaining ones serving as controls. The chickens were fixed by an aortic perfusion with 2.5% glutaraldehyde in phosphate buffer, pH 7.2. The treatment with oestrogen resulted in the following changes:

general increase in oviduct length and thickness,

differentiation of the epithelial membrane into three cell types: basal, apical and gland cells,

increase in the number of cilia in the apical cell, probably due to a new production of cilia,

formation of secretory granules in the vaginal epithelium as seen by light microscopy,

formation of proteinlike secretory granules in the apical cell as seen by electron microscopy,

increase in protein synthesis, observed as an augmentation of the endoplasmic reticulum.
ISOLATION OF 15α-HYDROXY-OESTRIOL FROM PREGNANCY URINE AND FROM THE URINE OF NEWBORN INFANTS
Authors: Zucconi G. , Lisboa B. P. , Simonitsch E. , Roth L. , Hagen A. A. , Diczfalusy E.
Published: December 2008

From the extracts of enzyme- or acid hydrolysed pregnancy urine and urine of newborn infants a new oestrogen metabolite has been isolated. On the basis of the physical and chemical characteristics of this compound it is concluded that it is identical with 15α-hydroxy-oestriol (oestra-1,3,5(10)-triene-3,15α,16α,17β-tetrol).
URINARY TESTOSTERONE EXCRETION IN MEN IN NORMAL AND PATHOLOGICAL CONDITIONS
Authors: Ismail A. A. A. , Harkness R. A.
Published: December 2008

The excretion of testosterone in the urine of men has been studied using the method of Ismail & Harkness (1966 a); the estimates obtained with this procedure, which has satisfactory reliability criteria, agree with those from the majority of published methods.

The effect of time, age, sexual activity, adrenal hyperfunction, hypopituitarism, undernutrition, precocious puberty, oligospermia and chlorpromazine administration have been investigated in a small number of subjects. All the above factors, except in the present case of oligospermia, are associated with alterations in testosterone excretion. The possible mechanisms and significance of these changes are discussed.
HORMONAL STUDIES OF A BENIGN INTERSTITIAL CELL TUMOUR OF THE TESTIS PRODUCING ANDROSTENEDIONE AND TESTOSTERONE
Authors: Wegienka Laurence C. , Kolb Felix O.
Published: December 2008

A case is described of a 14-year old male who presented with precocious puberty resulting from a benign slow growing interstitial cell tumour of the testis. Preoperative studies revealed a marked increase in urinary 17-ketosteroids, pregnanetriol and testosterone glucuronide. The urinary steroids showed little change following corticotrophin stimulation, dexamethasone suppression or chorionic gonadotrophin stimulation demonstrating the autonomous nature of this tumour. Although the urinary testosterone glucuronide levels were markedly elevated, the plasma levels of testosterone were normal and androstenedione elevated. These findings are in accord with in vitro findings of this tumour and support the premise that one of the primary metabolic products of this tumour was androstenedione which was peripherally transformed to testosterone glucuronide which was then excreted in the urine. The elevated 17-hydroxycorticosteroids and pregnanetriol, which returned to normal following removal of the tumour, together with the absence of any crystalloids of Reinke, suggest that the tumour may be of a biologically primitive cell type or of adrenal rest origin.
BONE AND URINARY HYDROXYPROLINE IN NORMAL AND HYPOTHYROID RAT WITH A LONG BONE FRACTURE
Authors: Kowalewski K. , Yong S.
Published: December 2008

Urinary excretion of hydroxyproline, considered as an index of collagen metabolism, was determined prior to, and during, a period of fracture healing in normal and hypothyroid rats. Hypothyroidism was induced by feeding the animals for eight months with a diet containing thiouracil (0.3%). A closed complete fracture of the humerus was produced and left unsupported for 28 days. At the end of this healing period, hydroxyproline of fractured and intact humerus was also determined. Significant increase of a saline extractable and total hydroxyproline was found in fractured bone of the normal rat and this was considered due to the synthesis of new collagen. No evidence of such a change in saline extractable hydroxyproline was found in hypothyroid rats. Significant progressive decrease of urinary hydroxyproline was found in hypothyroid rats during the period of fracture healing. Under the conditions of this experiment, evidence of deficient collagen synthesis and metabolism in hypothyroid rats is confirmed.
RADIOIODINE UPTAKE IN SUBACUTE THYROIDITIS DEVELOPING IN AN ENVIRONMENT OF ENDEMIC GOITRE
Authors: Weinstein M. , Soto R. J. , Flaster H. , Brunengo A. M. , Mendoza H. , Burian R.
Published: December 2008

Radioiodine parameters, mainly 131I uptake by the thyroid gland were reviewed in 31 cases of subacute thyroiditis (SAT). Seven cases presented depressed uptake. The remainder had either normal or high uptakes regardless of the phase of the disease during which the measurements were made. Fifteen subjects had lived in endemic goiter areas and 16 were from Buenos Aires where 131I uptakes are high and »subendemic« conditions prevail. It is thought that under these circumstances the inhibitory effect of SAT on 131I uptake as usually seen, does not become evident. PB131I and BE131I were normal in the subjects with normal or high 131I uptakes. It is concluded that radioiodine parameters in an endemic environment do not contribute to the diagnosis of SAT. The pathophysiology of SAT is discussed in the view of the present and related studies.
STUDIES ON THE PATHOGENESIS OF DIABETES IN ACROMEGALY
Authors: Luft Rolf , Cerasi Erol , Hamberger Carl Axel
Published: December 2008

Plasma insulin response to glucose infusion was found to be markedly increased in 20 patients with active acromegaly and with normal intravenous glucose tolerance. The insulin response was more pronounced in patients with highly active acromegaly than in those showing moderately active disease.

In five patients with active acromegaly and with decreased glucose tolerance the insulin response was delayed and smaller than normal, i. e. similar to that seen in diabetic subjects without acromegaly.

After successful treatment of the acromegaly insulin response to glucose infusion was normalized in the patients with normal glucose tolerance. In those with decreased glucose tolerance the diabetic type of insulin response remained unchanged even when the glucose tolerance was normalized.

It is suggested that diabetes in connection with acromegaly develops only in prediabetic individuals, i.e. subjects with decreased insulin response to hyperglycaemia, who are unable to overcome the diabetogenic effect of growth hormone by compensatory hyperinsulinism.
THE LIPID-MOBILIZING EFFECT OF SOME PITUITARY GLAND PREPARATIONS
Authors: Trygstad Olav
Published: December 2008

Lipid-mobilizing effect has been observed for nearly all the accepted pituitary hormones and for several suggested pituitary 'lipotrophins'. Pituitary hormone preparations are usually not homogeneous, and even a highly purified ACTH (p.ACTH) contains less than 30 per cent pure adrenocorticotrophin.

Crude ACTH (c.ACTH) was found to be 250 times more adipokinetic in rabbits than p.ACTH, indicating that this effect was mainly due to impurities.

A lipid-mobilizing fraction (LMFr) was precipitated from a human pituitary gland extract before the preparation of growth hormone and crude gonadotrophins, whereby the adipokinetic effect of these preparations in the rabbit became negligible. Removal of LMFr gave an electrophoretically purified growth hormone with reduced molecular weight and an increased somatotrophic potency per unit weight in a radioimmunoassay system.

Injection of the lipotrophic preparations into rabbits lowered the serum calcium level, and concentrations below 3 meq./l were observed, often accompanied by convulsions and in some instances by death.

It is concluded that the adipokinetic and hypocalcaemic effects of c.ACTH, p.ACTH and the employed human growth hormone preparations in rabbits may be due to contaminations. It is suggested that the LMFr contains a human pituitary lipotrophic factor which may also be responsible for the hypocalcaemia observed in the rabbit.
BLOOD GLUCOSE LEVEL IN MICE
Authors: Lundquist Ingmar , Rerup Claus
Published: December 2008

The hypoglycaemic effect of synthetic tetraicosapeptide corticotrophin was investigated in NMRI mice in order to determine its physiological significance as well as its mechanism of action. It was found that in normal non-fasting mice corticotrophin produced a maximal hypoglycaemic response at a dose level of about 5 μg per 20 g mouse (1250 milliunits per 20 g mouse). The ED50 of the hypoglycaemic effect was about 1000 times larger than the ED50 for adrenal cortical stimulation. Immunoassayable insulin was markedly increased 15 minutes following 5 μg of corticotrophin, whereas following a maximal steroidogenic dose (1.6 nanogram) or following ether stress the plasma insulin levels were normal. In adrenalectomized mice the administration of 5 μg of corticotrophin had practically no effect on the blood glucose level, whereas pretreatment with a glucocorticosteroid in adrenalectomized mice markedly restored the hypoglycaemic response. Acutely hypophysectomized mice showed a hypoglycaemic response to corticotrophin indistinguishable from that found in normal mice, whereas animals hypophysectomized 3–7 days before corticotrophin injection showed a smaller response.

Corticotrophin in a dose of 5 μg per 20 g mouse had no hypoglycaemic effect in mice with manifest alloxan diabetes. Corticotrophin injected 5 minutes following a diabetogenic dose of alloxan hardly had any measurable effect on the acute initial alloxan hyperglycaemia, whereas the latter was greatly reduced when corticotrophin was given 5 minutes before alloxan administration. Pretreatment with corticotrophin did not change the frequency or intensity of the ensuing diabetic condition in mice.

It is concluded that the corticotrophin induced hypoglycaemia is dependent on 1) the presence of normally functioning pancreatic beta-cells; and 2) the presence of glucocorticosteroids. It is doubtful whether the observed hypoglycaemia has any physiological significance.
THE METABOLIC EFFECT OF A SMALL UNIFORM DOSE OF HUMAN GROWTH HORMONE IN HYPOPITUITARY DWARFS AND IN CONTROL CHILDREN
Authors: Prader A. , Zachmann M. , Poley J. R. , Illig R.
Published: December 2008

The effect of small doses of human growth hormone (2 mg/m2 of HGH Raben daily) on the insulin-tolerance test in 15 hypopituitary and 10 control patients is described. With the dose used, fasting blood glucose levels and the response to insulin-induced hypoglycaemia are almost normalized in the hypopituitary patients and have only a slight effect on the control patients. The physiological dose of HGH and the diagnostic value of the insulin-tolerance test in hypopituitarism are discussed.