bluuebunny/crossref_metadata_2025 huggingface dataset:
RAPID DISAPPEARANCE OF LOADING DOSES OF THYROXINE FROM BLOOD AND THEIR EXCRETION BY THE BILE IN RATS
Authors: Langer Pavel , Kokešová Hana , Michajlovskij Nikolaj , Gschwendtová Klaudia , Hrčka Rudolf , Bukovská Mária
Published: December 2008

The disapperarance of loading doses of thyroxine (T4) (100–20 000 μg T4 iv per rat weighing about 400 g) was measured with the aid of new technique allowing frequent blood sampling with maintenance of isovolaemia in anaesthetized animals. It was found that as early as 2 min after the injection more than half of the administered dose disappeared from the blood, while after 300 min only about 2 % of that remained in the plasma. The direct relationship between the administered dose of T4 and both the relative and absolute level of free dialyzable T4 as well as of per cent of T4 displaced from the plasma by sodium salicylate in vivo was demonstrated. Moreover, it was found that about 60 % of administered T4 is excreted by the bile within 300 min irrespective of the dose given, about 15 and 50% of that being found in the small intestine after 15 and 180 min, respectively. When two loading doses of T4 were subsequently administered and labelled with different isotopes, the amount of T4 from the first dose excreted by the bile was proportional to the amount of T4 from a second dose administered 18 h later. From all these observations it was concluded that, in vivo, an effective system for removal of the loading doses of thyroxine from the blood exists, and is presumably located in rapidly equilibrating tissues, mainly in the liver. From this point of view it appears that plasma protein carriers play an important role in the whole body economy of thyroxine, namely by maintaining a certain level in the blood to cover the actual functional needs of peripheral tissues.
SOMATOMEDIN A AND B IN SERUM FROM NEONATES, THEIR MOTHERS AND CORD BLOOD
Authors: Svan H. , Hall K. , Ritzén M. , Takano K. , Skottner A.
Published: December 2008

Somatomedin A by radioreceptor assay and somatomedin B by radioimmunoassay were measured in serum from women immediately after parturition and from their newborns. The mean levels of somatomedin A in both mothers (0.54 U/ml) and infants (0.50 U/ml) were significantly decreased compared to a reference group consisting of 21 non-pregnant women (0.91 U/ml). There was no difference between the mothers and their children.

The mean somatomedin B value in serum from the mothers (63.9 μg/ml) was above that found in non-pregnant women (19.2 μg/ml) and the mean value in cord blood and serum from the infants (7.1 μg/ml) was below it. A positive correlation was noted between somatomedin A and B in cord blood; r = 0.78. The combined somatomedin A and B values in cord blood were positively correlated to birth weight (r = 0.51, P < 0.05).
SEX HORMONE BINDING GLOBULIN BINDING CAPACITY, TESTOSTERONE, 5α-DIHYDROTESTOSTERONE, OESTRADIOL AND PROLACTIN IN PLASMA OF PATIENTS WITH PROSTATIC CARCINOMA UNDER VARIOUS TYPES OF HORMONAL TREATMENT
Authors: Bartsch W. , Horst H.-J. , Becker H. , Nehse G.
Published: December 2008

Sex hormone binding globulin (SHBG) binding capacity, the concentrations of testosterone (T), of 5α-dihydrotestosterone (DHT), of oestradiol-17β (Oe2), of oestrone (Oe1), of prolactin (hPr) and the percentual specific binding of T to SHBG (% TB) were measured in plasma of patients suffering from prostatic carcinoma and of a control group of similar age. No significant differences in any of the investigated parameters were found between the control group and the carcinoma patients before treatment although 15 % of the latter showed distinctly elevated hPr values. Treatment of carcinoma patients with

1) Antiandrogen (cyproterone acetate, Androcur®) resulted in a significant decrease of T, Oe2 and SHBG. The DHT/T-ratio increased. n = 5.

2) Orchidectomy caused an even more pronounced fall in T, DHT, Oe1 and Oe2 blood levels. SHBG was not altered. DHT/T-ratio increased. n = 32.

3) Cyproterone acetate after orchidectomy led to elevated hPr values. n = 5.

4) Oestrogen (diethylstilboestrol-diphosphate, Honvan®) after orchidectomy increased SHBG and hPr. n = 6.

5) Corticosteroid (Prednisone, Decortin®) after orchidectomy decreased T and SHBG below the levels found after orchidectomy alone, n = 5.

6) Diureticum (Mefruside, Baycaron®) (n = 5) or

7) a placebo (n = 7) did not alter any of the parameters measured.

8) Treatment with HCG (Primogonyl®) of patients suffering from oligozoospermia resulted in a significant increase of T, DHT and Oe2. SHBG was not altered. DHT/T-ratio decreased, n = 7.
CONTRIBUTION OF LACTIC ACID BY THE AMPULLARY AND ISTHMIC PARTS OF RABBIT FALLOPIAN TUBE UNDER ALTERED HORMONAL CONDITIONS
Authors: Misra Deepa , Gupta D. N. , Karkun J. N.
Published: December 2008

The capability of the ampullary and isthmic parts of the rabbit Fallopian tube to contribute lactic acid (LA) to the tubal lumen was examined using an in vitro method of study. In addition concomitant study was also made using the uterus.

It was found that in the oestrous rabbit, the isthmus contributed LA at a higher rate than that of the ampulla; the uterine contribution was minimal.

Ovariectomy reduced while exogenous oestrogen enhanced this ability in all the three tissues.

In mated post-ovulatory rabbits the contributory efficiency of either tubal part changed and appeared to exhibit a peak value in the presence of the ovum; the uterus showed no such changes. This is discussed in relation to the ability of the egg to secure its energy source until it attained morula/the pre-blastocyst stage.
THYROID FUNCTION AND PLASMA CYCLIC AMP RESPONSE TO INTRAVENOUS GLUCAGON
Authors: Madsen S. Nistrup
Published: December 2008

The glucagon stimulated increase in plasma cyclic AMP has been studied in 17 healthy subjects, in 13 hyperthyroid and in 14 hypothyroid patients. Six hyperthyroid and 2 hypothyroid patients were re-investigated after at least 15 months of treatment. The results show:

1) The glucagon stimulated cyclic AMP response is significantly increased in hyperthyroid patients considered as a group, and is reduced in patients with hypothyroidism.

2) Three hyperthyroid and 4 hypothyroid patients showed a normal response to iv glucagon, indicating that the plasma cyclic AMP response to iv glucagon is not a sensitive test for the evaluation of peripheral thyroid states. This suggests that the effects of thyroid hormones in the liver does not necessarily follow the effects in other tissues.

3) Re-investigation of treated patients showed that the cyclic AMP response can be normalized by treatment, both in hyperthyroidism and in hypothyroidism. However, in patients treated for hyperthyroidism a hyper-response to glucagon can continue after blood levels of thyroid hormones are reduced to normal.

This suggests an inertia in the loss of the hyper-response to glucagon, once a hyperfunction has been induced. A similar inertia in the loss of glucagon sensitivity in hypothyroidism could explain the large number of normal tests in hypothyroid patients.
EFFECTS OF AMIODARONE ON THYROID IODINE METABOLISM IN VITRO1)
Authors: Gluzman Bernardo E. , Coleoni Aldo H. , Targovnik Héctor M. , Niepomniszcze Hugo
Published: December 2008

Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,5- diiodo, benzoyl) benzofuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10−4 m and 10−5 M, showing a decrease of T/M (tissue/medium) ratios of 20% and 23%, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10−4 m and 10−5 m amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20% decrease at 10−3 m amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7% at a concentration of 10−4 m. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10−3 m and 10−4 m. The inhibitions were of 22.5% and 16.8%, respectively.

We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.
EFFECT OF INSULIN AND ADRENALINE ON CYCLIC AMP IN THE DIAPHRAGM OF NORMAL AND DIABETIC RATS
Authors: Edén Staffan , Albertsson-Wikland Kerstin , Rosberg Sten , Isaksson Olle
Published: December 2008

The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline.

The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.
CORRELATION BETWEEN RISES OF GONADOTROPHINS AND RISES OF SEX STEROIDS DURING CLOMIPHENE TEST IN MEN
Authors: Johnsen Svend G. , Jørgensen F. Schønau , Kampmann Jens P. , Bennett Paul , Micic Snezana , Svenstrup Birgit
Published: December 2008

Serum FSH, LH and testosterone and urinary excretion of androsterone, aetiocholanolone, dehydroepiandrosterone and total oestrogens were measured in normal and oligospermic men before and after clomiphene stimulation. Responses in all parameters were highly variably from one individual to another and this great variation formed the basis for investigating the correlations between responses. There was no correlation between increase of FSH and LH or increase of LH and steroids. Also there was no correlation between rises of FSH and rises of androgens. But a significant correlation existed between rises of FSH and rises of oestrogens. This confirms that one action of FSH is to stimulate production of testicular oestrogens which presumably takes place in the Sertoli cells.
CORRELATIVE STUDY OF RADIORECEPTOR ASSAY AND RADIOIMMUNOASSAY OF SERUM GROWTH HORMONE IN CHILDREN: NORMAL CHILDREN AND HGH -TREATED PITUITARY DWARFS
Authors: Garnier Philippe E. , Job Jean-Claude , Repellin A. M.
Published: December 2008

A sensitive and reproducible radioreceptor assay (RRA) for human growth hormone (HGH) is described. It allows the evaluation of HGH concentrations as low as 2 ng/ml. It has a limited cross-reactivity with human prolactin, which does not interfere at physiological levels in children. Comparison of the results with those of radioimmunoassay (RIA) showed no discrepancies in the serum of normal children before and after stimulation tests for GH (mean RRA/RIA ratio 1.03 ± sem 0.04, range 0.75 to 1.65) nor in the serum from hypopituitary dwarfs during the 12 h following an im injection of 6 mg of HGH (mean RRA/RIA ratio 1.05 ± sem 0.04, range 0.84 to 1.28). It is concluded that receptoractivity of HGH is parallel to its immunoreactivity in normal children and in hypopituitary patients receiving clinical grade HGH.
CELL-MEDIATED AUTOIMMUNITY IN THYROID DISEASE AS STUDIED BY THE LEUKOCYTE MIGRATION TEST; CORRELATION TO CLINICAL STATE AND EFFECT OF TREATMENT
Authors: Tötterman T. H. , Mäkinen Tuulikki , Gordin A.
Published: December 2008

We have used a modified leukocyte migration test (LMT) for the study of cell-mediated immunity (CMI) against thyroid antigen in 100 thyroid patients and 20 healthy controls. In 57 cases of Graves' disease, the greatest mean inhibition of leukocyte migration was seen in untreated, hyperthyroid patients as compared with patients treated with thyrostatic drugs, radioiodine or surgery. The differences in means between untreated and treated patients were not, however, significant, but the number of patients with a positive LMT (i. e., showing significant inhibition) was greater in the untreated group (92 %) than in the treated groups (50–77 %). Four out of 5 patients with euthyroid Graves' disease were positive. It is concluded that the LMT cannot be used to predict remission in Graves' disease. In the present study, 9 out of 12 cases with toxic nodular goitre had a positive LMT, and there was no difference in mean migration between treated and untreated patients. In 9 cases of symptomless autoimmune thyroiditis the distribution of leukocyte migration was dual: 6 showed significant inhibition and 3 significant stimulation, indicating evidence of CMI in this disease as well. Furthermore, 10 out of 14 cases with spontaneous primary hypothyroidism showed inhibition in the LMT, and there was no difference between untreated cases and cases euthyroid on substitution therapy. Eight patients with non-toxic goitre served as "thyroid controls", and they were all negative in the test.
ISOLATION OF TSH-RESPONSIVE HUMAN THYROCYTES-ANALYSIS OF VARIOUS THYROID TUMOURS
Authors: Breustedt Hans-Jörg , Nolde Siegmar , Schumacher Matthias , Hilz Helmuth
Published: December 2008

A method for the isolation of hormone-responsive thyrocyte suspensions from human tumours is described.

Cells from normal and adenomatous thyroid tissue responded to thyroid stimulating hormone (TSH) by a concentration-dependent increase in cAMP. Bovine TSH usually produced half-maximal elevation of cAMP levels at concentrations between 2 and 4 mU/ml. Human TSH caused half-maximal stimulation at 3–8 times lower concentrations indicating considerable species specificity of the human TSH receptor. Other hormones were without influence except prostaglandin E1 (PGE1) which evoked moderate elevations of the cAMP levels.

Kinetic analyses of various thyroid tumours revealed marked differences in TSH induced increases in the intracellular cAMP levels with respect to the time course as well as to the extent of the maximal response. Theophylline, which by itself had a rather small effect on basal cAMP levels, acted synergistically with TSH in most cases, leading to values up to 20 times above the control values. The kinetics also indicated the existence in stimulated cells of two cAMP pools exhibiting different susceptibility to phosphodiesterase.

Cells from adenomatous goitres with hyperplasia exhibited significantly lower basal cAMP levels than thyrocytes from the other goitres and from normal tissue. Other classes of thyroid tumours also showed characteristic differences with regard to basal cAMP and degree of stimulation by TSH and theophylline.
THE OESTROUS CYCLE OF THE COW: HORMONAL PARAMETERS AND TIME RELATIONSHIPS CONCERNING OESTRUS, OVULATION, AND ELECTRICAL RESISTANCE OF THE VAGINAL MUCUS
Authors: Schams D. , Schallenberger E. , Hoffmann B. , Karg H.
Published: December 2008

A synopsis is presented of hormonal profiles (peripheral plasma values of LH, FSH, progesterone; urinary oestrogens) during the oestrous cycle of cattle. After ovulation (day one) progesterone levels begin to increase from about day 4, reach a plateau around day 10, and decrease to basal concentrations starting on days 17 to 18. Corresponding with the progesterone decrease, urinary oestrogens show a main increase reaching its maximum one day before ovulation. LH levels are fairly constant from ovulation until day 5, small but significant peaks can be observed between days 6 and 10 in some cows (6 out of 21) and levels then decrease from day 11 to 13. A gradual additional increase begins on day 17, resulting in the preovulatory LH peak 25.7 ± 6.9 h (n = 75) before ovulation. This peak has a duration of 7.4 ± 2.6 h (n = 89) and occurs any time of the day but preferentially around 8 a. m. and 8 p. m. respectively. Likewise related are the two main periods for ovulation. During oestrus, (average duration of 16.9 ± 4.9 h (n = 28) the electrical resistance of the vaginal mucus decreases and the lowest values always correspond with the LHpeak. FSH levels show a wavelike pattern with peaks around days 4, 8, 12–13, 17, 18 and also coinciding with the pre-ovulatory LH peak. The sharp decrease in FSH between the two peaks on days 17 and 18 correlates with the decrease of progesterone during luteolysis. Obviously there is a parallelism between FSH elevations and follicular growth (determined by means of pelviscopic observations).
CIRCADIAN RHYTHM OF PLASMA TESTOSTERONE IN THE MALE DJUNGARIAN HAMSTER (PHODOPUS SUNGORUS)
Authors: Hoffmann Klaus , Nieschlag Eberhard
Published: December 2008

A marked circadian rhythm of plasma testosterone was found in male Djungarian hamsters. Maximal values in the evening just prior to activity onset were about 12 times higher than minimum values in the early morning. The peak of serum testosterone concentration coincides with onset of oestrus in females.
PUBERTAL MANIFESTATION OF SEX DIFFERENCE IN CIRCADIAN RHYTHM OF CORTICOTROPHIN-RELEASING ACTIVITY IN THE RAT HYPOTHALAMUS
Authors: Honma Sato , Hiroshige Tsutomu
Published: December 2008

Post-natal development of the circadian rhythm of hypothalamic content of corticotrophin-releasing factor (CRF) was examined in male and female rats, separately. CRF activity was estimated by the intrapituitary injection technique. The circadian rhythm of the CRF content observed at the third week was without any noticeable sex difference: both male and female rats began their circadian rhythm with higher values in the afternoon than in the morning. Male rats maintained this pattern up to maturity. In contrast, female rats showed a marked change at ages of fifth to sixth week: the CRF rhythm in female rats changed to a female pattern, with higher values in the morning than in the afternoon. During this period, the vaginal opening occurred concurrently with a marked afternoon rise in the plasma corticosterone, characteristic of mature female rats. On the other hand, no essential difference could be observed between male and female rats in the developmental change in the circadian rhythm of locomotor activity. These results indicate that a sex difference in the CRF rhythm is not essentially related to the process of sex differentiation in the central nervous system, but is rather related to changes in ovarian activity following the onset of puberty.
STIMULATING ACTION OF SULPIRIDE AND PIMOZIDE ON PROLACTIN RELEASE EFFECT ON BROMOCRIPTINE, L-DOPA AND METERGOLINE ADMINISTRATION
Authors: Delitala Giuseppe
Published: December 2008

In order to evaluate the mechanism of action of metergoline, an antiserotonin agent, the effect of pre-treatment with metergoline on prolactin (PRL) release induced by sulpiride was compared to that obtained after bromocriptine administration in normal subjects. In addition, the metergoline effect on PRL release induced by pimozide, specific dopamine receptor blocking agent, was compared to that obtained with L-dopa.

Metergoline administration resulted in definite decrease in plasma PRL in all subjects; however, metergoline did not block, differently from bromocriptine, the PRL release induced by sulpiride. On the contrary, metergoline, like L-dopa, inhibited PRL release induced by pimozide pre-treatment.

These results raise the possibility that metergoline does not act as an antiserotonin agent; its antilactogenic effect observed under basal conditions may be dependent on different mechanisms of action.
POSITIVE FEEDBACK ACTION OF OESTRADIOL ON GONADOTROPHIN RELEASE IN 15 DAY OLD FEMALE RATS
Authors: Kronibus J. , Wuttke W.
Published: December 2008

Female rats were ovariectomized (ovx), adrenalectomized (adx) or both (adx-ovx) on day 8 after birth. The serum gonadotrophin concentrations on day 15 were higher in ovx and adx-ovx rats than in sham-operated or untreated controls of the same age. Intact animals on day 15 had higher LH and FSH levels compared with adult, dioestrous levels, and a number of LH peaks were observed. After partial separation of oestradiol (LH 20 column chromatography) from other lipid substances which interfere with the radioimmunoassay for oestradiol, levels of oestradiol were undetectable in ovx and in adx-ovx animals on day 15 but concentrations were relatively high in intact or adx rats.

To test whether the high gonadotrophin concentrations in 15-day-old intact rats were due to a positive feedback action of oestradiol, silastic tubes containing different amounts of oestradiol were implanted on day 8 at the time of adrenalectomy and ovariectomy. The mean serum LH and FSH concentrations were increased on day 15 in those animals in which silastic tube implantation resulted in physiological oestradiol levels. These elevated gonadotrophin values were due to a number of peak levels. Injection of 600 μg progesterone on day 15, 8 h before decapitation resulted in high FSH levels in all the implanted animals, whereas LH levels were still variable from one animal to another. This situation is very similar to that in intact control rats and it is concluded that the hypothalamo-pituitary axis in 15-day-old female rats reacts to an oestrogenic stimulus followed by a progestational reaction as does the adult "gonadostat". This would account for the premature, pre-ovulatory type of LH peaks.
RADIOIMMUNOASSAYS OF TETRAHYDROCORTISONE AND TETRAHYDROCORTISOL IN HUMAN URINE
Authors: Will H. , Aderjan R. , Winkler Th. , Penke B. , Vecsei P.
Published: December 2008

A simple radioimmunoassay for the determination of tetrahydrocortisone (THE)1), and tetrahydrocortisol (THF) as well as their 21-glucosiduronate conjugates is described.

White New Zealand rabbits were immunized with THF- and THE-20-oxime-bovine serum-albumin conjugates. The resulting antisera proved to be very specific. Both allo-THE and allo-THF gave minimal cross-reactions; however, THE- and THF-21-glucosiduronate bind with the corresponding antibodies at a level of 100 %.

The following types of estimations were introduced:

a) Estimation of the sum of unconjugated THF and THF-21-glucosiduronate in highly diluted unprocessed human urine.

b) A similar estimation of THE and THF-21-glucosiduronate as in a).

c) Estimation of THF after β-glucuronidase treatment and dilution without further procedures.

d) A similar estimation for THE as in c).

THF and THE values correlate significantly with known parameters that characterize the cortisol production, such as cortisol secretion rate and the urinary corticoid (C21-α-ketolic-steroid) levels.
LACTATE CONCENTRATIONS IN PRE-OVULATORY FOLLICLES OF PRO-OESTROUS RATS BEFORE AND AFTER ONSET OF OOCYTE MATURATION
Authors: Zeilmaker G. H. , Verhamme C. M. P. M.
Published: December 2008

Lactate concentrations were determined in pre-ovulatory follicles of rats at pro-oestrus before and after onset of oocyte maturation. It appeared that high concentrations prevail before and after the time of the expected LH surge (27 mM). The level in serum was about 5 mm. Explanted oocytes obtained from pre-puberal rats and surrounded by cumulus cells, matured in the presence of 20 mm. lactate as sole exogenous energy source. It is argued that oxygen may be the limiting factor suppressing oocyte maturation in vivo.
AGE DEPENDENCE OF TESTOSTERONE PRECURSORS IN PLASMA OF NORMAL ADULT MALES
Authors: Pirke Karl M. , Doerr Peter , Sintermann Rainer , Vogt Hermann J.
Published: December 2008

Radioimmunoassays for the measurement of pregnenolone1), 17α-hydroxy-progesterone, androstenedione, dehydroepiandrosterone (DHEA) and androstenediol (5-androstene-3β,17β-diol) have been developed. In addition the reliability criteria of these methods have been established.

Age dependence of testosterone precursors in plasma was studied in 80 normal males aged 19 to 93 years. When a young to middle aged group (19–54 years) was compared with an old age group (67–93 years) a highly significant (P < 0.001) decrease was observed for all the precursors studied: DHEA −68.1%, pregnenolone −60.3%, androstenediol −53.8%, 17α-hydroxyprogesterone −47.5% and androstenedione −39.2%.

Nine old patients (60–81 years) with prostatic carcinoma were studied before and 1 week after therapeutic castration. The results indicate that approximately 73% of the peripheral 17α-hydroxyprogesterone, 55% of the androstenediol, 52 % of the pregnenolone, 31 % of the androstenedione and 27 % of the DHEA are of testicular origin in old men with prostatic cancer. HCG-stimulation tests were performed in 12 young (21–30 years) and 12 old (69–83 years) men. There was no significant increase in pregnenolone and in DHEA in both age groups. The relative increase of 17α-hydroxyprogesterone, androstenedione and androstenediol did not differ between young and old men. The absolute increase of androstenedione and androstenediol was twice as high in the young men.
BROMOCRIPTINE TREATMENT IN ACROMEGALY: CLINICAL AND BIOCHEMICAL EFFECTS
Authors: Halse Johan , Haugen Harry N. , Bøhmer Thomas
Published: December 2008

Eight selected patients with active acromegaly and elevated GH levels without other endocrine disturbances were submitted to long-term treatment and acute dose-response trials with bromocriptine. Seven patients showed clinical improvement and lowering of GH levels in response to long-term treatment, however, two of these showed only minor changes in GH levels during the acute dose-response trial. Glucose tolerance and heel pad thickness remained unchanged, while urinary hydroxyproline excretion and blood, plasma and erythrocyte volumes decreased.

Using daily doses of 20 mg bromocriptine, side effects were generally minor. Severe vasovagal reactions were, however, observed in two patients, in one at the start of treatment, in the other after ingestion of 25 mg bromocriptine.

Bromocriptine represents a valuable treatment alternative in acromegaly, but only long-term treatment will separate responders from nonresponders.
SUBACUTE THYROIDITIS DE QUERVAIN: A DISEASE ASSOCIATED WITH A HLA-B ANTIGEN
Authors: Bech Karine , Nerup Jørn , Thomsen Mogens , Platz Per , Ryder Lars P. , Svejgaard Arne , Siersbæk-Nielsen Kaj , Hansen Jens E. Mølholm
Published: December 2008

Twenty-four caucasian patients with subacute thyroiditis de Quervain were HLA-A, B, C and D typed to evaluate a possible association between the major histocompatibility system and this disease. A highly increased frequency of HLA-Bw35 could be demonstrated (71 per cent, P = 2 × 10−10, relative risk 16.2) together with a concomitant increase of Cw4 (54 per cent, P = 7.9 × 10−5, relative risk 5.7), while the HLA-D antigen Dwl was only moderately and insignificantly increased. Accordingly, this disorder is more strongly associated with HLA-B than HLA-D segregant series in contrast to most other HLA associated diseases. The HLA association proves that the susceptibility to develop subacute thyroiditis de Quervain is genetically influenced, and suggests that HLA-typing may be of value in the diagnosis.
ORPHENADRINE (DISIPAL), SERUM THYROXINE AND THYROID FUNCTION
Authors: Wiersinga W. M. , Fabius A. J. M. , Touber J. L.
Published: December 2008

Studies were undertaken to elucidate whether orphenadrine influences thyroid function. Seven volunteers were given orphenadrine in weekly increasing dosage up to 300 mg per day; in 5 patients chronically treated with 300 mg orphenadrine daily the drug was gradually discontinued. No changes were found in PBI, RT3U, TT3 and TSH during or after orphenadrine medication; also TSH- and TT3-responses to 200 μg TRH iv were not influenced by the drug. Orphenadrine medication increased serum thyroxine values (P < 0.001) as measured with the competitive protein binding (CPB) technique, but did not influence serum thyroxine values measured by radioimmunoassay. Orphenadrine added to serum in vitro in the Murphy-Pattee assay did not increase thyroxine values; two out of eight tested metabolites however did. It is concluded that orphenadrine in a dosage up to 300 mg per day does not influence thyroid function. It increases serum thyroxine levels as measured by the competitive protein binding technique of Murphy and Pattee. This is due to an in vitro competition between ethanol-extractable orphenadrine metabolites and thyroxine for binding sites on the thyroxine binding globulin.
THE EFFECT OF 1,25-DIHYDROXYCHOLECALCIFEROL ON THE PARATHYROID HORMONE SECRETION OF PORCINE PARATHYROID GLANDS AND HUMAN PARATHYROID ADENOMAS IN VITRO
Authors: Altenähr E. , Dietel M. , Dorn G. , Montz R.
Published: December 2008

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) on parathyroid hormone secretion by porcine parathyroid glands and human parathyroid adenoma tissue was investigated by in vitro incubation. The addition of 100 nmoles 1,25-(OH)2-D3 to the medium inhibited significantly the release of immunoreactive parathyroid hormone by 63–65 %. This suppression was reversible when 1.25-(OH)2-D3 was removed again. The inhibition of parathyroid hormone release observed in human parathyroid adenoma tissue was similar to that in normal porcine parathyroid glands. This indicates that adenoma tissue is sensitive to regulatory influences. As well as calcium, 1,25-(OH)2-D3 may act as another feedback inhibitor of parathyroid hormone secretion.
IONIC EFFECTS ON THE UPTAKE OF CHLOROMERCURIBENZENE-p-SULPHONIC ACID BY PANCREATIC ISLETS
Authors: Söderberg Monica , Täljedal Inge-Bert
Published: December 2008

Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-non-displaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that β-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO42−. By analogy with existing models of the erythrocyte membrane, it is suggested that the SO42−-sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in β-cells.
MICROCHEMICAL ASSAYS OF GLUTATHIONE, ZINC, COBALT AND MANGANESE IN MICRO-DISSECTED AREAS OF THE ENDOCRINE PANCREAS IN THE HAGFISH, MYXINE GLUTINOSA
Authors: Havu Niilo , Lundgren Gillis , Falkmer Sture
Published: December 2008

In hagfish islet parenchyma, consisting practically only of insulin-producing B-cells and agranular B-cell precursors, the contents of glutathione (GSH) and total protein-free thiols (NPSH) were determined on micro-dissected islet lobules. GSH was found to be of the same order of magnitude (22–25 mg/100 g wet weight) as in the islet parenchyma of a previously studied teleost fish and of some mammals, including man. However, the NPSH was found to be considerably higher in the islet lobules of the hagfish than in the teleostean islet parenchyma. As in both teleost fish and mammals, GSH made up most of the NPSH in the hagfish erythrocytes, myocardium, and skeletal musculature. This discrepancy between hagfish islet parenchyma and other tissues indicates that the non-GSH portion of NPSH may be of particular significance for the insulin-producing B-cells.

By means of flameless atomic absorption spectrophotometry the contents of zinc, cobalt, and manganese were determined in micro-dissected hagfish islet lobules. Neither zinc, nor cobalt, occurred in significantly higher concentrations in the islet parenchyma than in the liver or the skeletal musculature. Only manganese was found in somewhat higher amounts in the islet lobules than in the other tissues, but the contents were still low. The results indicate that none of the three heavy metals play any important role in the synthesis, storage, or release of insulin in the hagfish.

The significance of this in relation to the prevailing hypotheses regarding the pathogenesis of alloxan diabetes is discussed.
METABOLIC AND HORMONAL EFFECTS OF POST-MENOPAUSAL OESTROGEN REPLACEMENT TREATMENT
Authors: Larsson-Cohn Ulf , Wallentin Lars
Published: December 2008

Glucose, insulin and growth hormone (GH) levels were measured during 3 h oral glucose tolerance tests, performed in two groups of post-menopausal women. Nineteen subjects were given ethinyloestradiol (EOe) 0.05 mg daily and 20 received oestradiol valerianate (OeV) 2 mg daily. The tests were performed twice before treatment and after 1, 3 and 6 cycles of medication.

EOe induced a slight but statistically significant deterioration of the glucose tolerance concomitant with a tendency to elevated insulin levels. The women taking OeV showed no significant alteration of the glucose or insulin levels. The GH concentrations were increased in both groups although the elevation was more pronounced in those taking EOe. The reduced carbohydrate tolerance was not believed to have been responsible for the raised GH levels.
STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE
Authors: Landgren B.-M. , Campo S. , Cekan S. Z. , Diczfalusy E.
Published: December 2008

The variation of the plasma levels of 11 steroids and LH was investigated in 6 normally menstruating women during the peri-menstrual period. Blood was withdrawn continuously over a period of 42 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The changes in hormone levels were studied during 14 3-h sampling periods (42 h) which - with respect to the clock time - were identical in all subjects.

Cortisol, 17-hydroxypregnenolone and dehydroepiandrosterone exhibited a marked circadian rhythm with the highest mean levels in the morning between 06.00 and 09.00 h and the lowest mean levels during the night between 21.00 and 03.00 h. The amplitude of the variation was high, the differences between the highest and lowest values being 200, 590 and 150%, respectively. Also the coincidence of individual peak values with the average peaks was high (mostly in 5 out of 6 cases). The correlation of cortisol levels with those of 17-hydroxypregnenolone and dehydroepiandrosterone was significant (r = 0.79 and 0.59, respectively; P < 0.001).

The circadian variation of 17-hydroxyprogesterone, androstenedione and pregnenolone was also significant, but less pronounced, as indicated by lower amplitudes and larger spread of individual peaks around average peaks. The correlation of the levels of these steroids with those of cortisol was significant (r=0.47 P<0.001; r=0.44 P<0.001 and r=0.31: P<0.01, respectively).

Progesterone, 20α-dihydroprogesterone, testosterone and oestradiol did not exhibit any circadian variation, but a steady decrease of levels. The levels of the first two steroids were significantly correlated (r = 0.81; P < 0.001).

The dihydrotestosterone and LH levels did not show any significant changes during the entire study. If, however, only the second half of the sampling time was statistically analysed, a significant increase was found in the LH levels. During this time the LH levels were negatively correlated with the decreasing levels of progesterone and 20α-dihydroprogesterone (r=−0.59 and −0.66, respectively; P < 0.001).

A comparison of the data with those of a previous study performed during the peri-ovulatory period suggests that the occurrence, intensity and regularity of the circadian rhythm varies according to different phases of the menstrual cycle. The data also suggest that 17-hydroxypregnenolone in plasma is an excellent indicator of adrenocortical activity.
SERUM GONADOTROPHINS, TESTOSTERONE AND SPERMATOGENESIS IN SUBFERTILE MEN
Authors: Aafjes J. H. , van der Vijver J. C. M. , Docter R. , Schenck P. E.
Published: December 2008

In 210 subfertile men there existed a significant positive correlation between serum FSH and LH (0.41). No correlation was observed between the gonadotrophin levels and testosterone. In contrast to this FSH as well as LH were negatively correlated with the natural logarithm (In) of the sperm count/ml ejaculate (−0.44 and −0.18, respectively). When the positive correlation which existed between FSH and LH was used to calculate partial correlation coefficients, the coefficient between FSH and ln sperm count did hardly change (−0.41) the coefficient between LH and ln sperm count on the other hand became insignificant (−0.05). This suggests that spermatogenesis influences FSH serum levels in subfertile men by a decreased suppression when sperm production is diminished.

Testicular biopsies taken from 97 of these patients were used to determine biopsy scores. These scores showed a significant negative correlation with FSH (−0.34) and a positive one with ln sperm count/ml ejaculate (0.45). Interestingly the biopsy score of 16 patients who fertilized their wives, was found to be higher compared with the score of the other patients who did not fertilize. The number of sperm/ml ejaculate and the FSH values of these 2 groups of biopsied patients were, however, not significantly different. This leads to the conclusion that the biopsy score is a better parameter for the evaluation of oligospermic men than either sperm count or FSH serum values.
CHANGES IN INSULIN RECEPTOR CONCENTRATION IN RAT FAT CELLS FOLLOWING TREATMENT WITH THE GESTAGENS CLOMEGESTONE ACETATE AND CYPROTERONE ACETATE
Authors: Krauth M. C. , Schillinger E.
Published: December 2008

Specific insulin receptors were measured in isolated fat cells of rats after treatment with clomegestone acetate1). Under conditions when peripheral insulin insensitivity was observed, the number of insulin receptors was simultaneously reduced. A similar though smaller decrease in insulin receptor concentration was seen in rats after treatment with cyproterone acetate, a compound which did not cause insulin resistance.

It is concluded that the gestagenic compounds tested decrease insulin receptor concentration. Only drastic reduction of the number of binding sites results in significant perturbations of carbohydrate metabolism.
HYPERPROLACTINAEMIA IN AMENORRHOEA - INCIDENCE AND CLINICAL SIGNIFICANCE
Authors: Bergh Torbjörn , Nillius Sven Johan , Wide Leif
Published: December 2008

Prolactin concentrations in serum were determined in 287 women with amenorrhoea. The incidence of hyperprolactinaemia was 14.6 per cent. All but 4 of the 31 women with persistent hyperprolactinaemia had galactorrhoea. Radiological signs suggestive of a pituitary tumour were seen in 48 per cent of the hyperprolactinaemic women, while only 4.5 per cent of the 245 normoprolactinaemic women had abnormal sellar X-rays. All the patients with prolactin concentrations above 100 μg/I had radio-logically abnormal sellae, but lower prolactin levels did not rule out the existence of even large pituitary tumours. The hyperprolactinaemic women with normal and abnormal sellae and a control group of healthy women in the early follicular phase all had similar mean basal FSH and LH levels with one exception, the group with abnormal sellae had lower basal LH levels than the control group. There was no difference in the mean FSH and LH responses to LH-RH between the hyperprolactinaemic women with pathological sellae and the control group while the hyperprolactinaemic women with normal sellae had higher responses than the other two groups. Prolactin determinations were found to be superior to other pituitary hormone estimations for identifying patients who are at risk of having pituitary tumours.
ASSAYS FOR ANTIGEN-STIMULATED LYMPHOCYTE-DERIVED MIGRATION ENHANCEMENT AND INHIBITION FACTORS FROM PATIENTS WITH THYROID DISEASES AND THEIR RELATIVES
Authors: Matsui Yukio , Beall Gildon N. , Chopra Inder J. , Solomon David H. , Kruger Sally , Beall Marie
Published: December 2008

Cell-mediated immunity to thyroid antigens was studied by means of an assay for antigen-stimulated leukocyte migration inhibition factor (LIF) in 5 groups of subjects: patients with Graves' disease, Hashimoto's thyroiditis, their relatives and normal controls. We also sought evidence for the possibility that the hypothesized migration enhancement factor (MEF) might be produced by lymphocytes from patients with autoimmune disorders.

We found little evidence of LIF production and none of MEF production by the leukocytes of patients with autoimmune thyroid diseases upon exposure to thyroid antigens. Similarly, either no or only minimal amounts of LIF were demonstrated in culture supernatants of leukocytes of their immediate relatives.
HLA-BW35 AND B5 IN JAPANESE PATIENTS WITH GRAVES' DISEASE
Authors: Kawa A. , Nakamura S. , Nakazawa M. , Sakaguchi S. , Kawabata T. , Maeda Y. , Kanehisa T.
Published: December 2008

Thirty-three Japanese patients with Graves' disease and 106 healthy controls living in the Kagoshima area, the southernmost part of the Japanese mainland, were HLA typed by the NIH method. None of them were related to each other.

The only antigen showing an increased frequency in Japanese patients with Graves' disease was HLA-BW35 (corrected P < 0.02). A decreased frequency of B5 in the patients was also statistically significant (corrected P < 0.02).
TSH AND CATECHOLAMINES: INDEPENDENT EFFECTS ON ACTIVE TRANSPORT AND IODINE ORGANIFICATION IN ISOLATED THYROID CELLS
Authors: Maayan Morelly L.
Published: December 2008

Catecholamines greatly stimulated iodine organification in thyroid
cells isolated by trypsinization but failed to increase the
cell-medium (C/M) ratio of 131I− or 99mTcO4− in the same cells preparation. Both TSH and catecholamines increased the concentration of organified iodine in thyroid cell despite the presence of active transport inhibitors, suggesting either the existence of a second thyroidal transport system or the possibility of an accelerated entry of anions into thyroid cells in the presence of stimulatory agents
VARIATIONS IN UTERINE CYTOSOLIC OESTROGEN AND PROGESTERONE RECEPTOR LEVELS DURING THE RAT OESTROUS CYCLE
Authors: Kielhorn Janet , Hughes Alun
Published: December 2008

The levels of cytosol receptors for both oestradiol and progesterone were simultaneous monitored in the uterus at various stages of the rat oestrous cycle. The use of the synthetic gestagen R-5020, with its high specificity and affinity for the progesterone receptor, eliminated interference arising from corticosteroid binding globulin (CBG) contamination of uterine extracts. The results show that the patterns for both receptors are markedly different over the cycle. The variation can be correlated with changes in ovarian steroid output. The results also suggest that oestradiol and progesterone interact not only with their specific receptor, but also influence the other receptor system.
CORRELATION BETWEEN PER CENT DISCHARGE OF THIOCYANATE TEST AND THYROID FUNCTIONS IN PATIENTS WITH HASHIMOTO'S DISEASE
Authors: Yamamoto Makiko , Saito Shintaro , Sakurada Toshiro , Yoshida Katsumi , Kaise Kazuo , Kaise Nobuko , Yoshinaga Kaoru
Published: December 2008

The thiocyanate test was carried out in 18 patients with Hashimoto's disease. Thiocyanate was given orally several hours after the administration of tracer doses of 131I when the thyroid counts seemed to have reached a plateau. The per cent discharge of thiocyanate test was significantly higher in the groups with lower level of T4 (< 5.5 μg/100 ml), RSU (<25.5%) and BMR (<+2.5 %), and higher levels of TSH (> 10.0 μU/ml). A chi-square (ϰ2) test with Yates correction led to ϰ2 = 3.56 (1 df) with P=0.06 (per cent discharge vs T4, RSU, BMR and TSH). Then the per cent thiocyanate discharge was increased with the degree of hypothyroidism in patients with Hashimoto's disease. The correlation between the per cent discharge and 131I 24 h uptake was not significant. It was apparent that the iodide concentration mechanism was present even in the severe hypothyroid stage of Hashimoto's disease. This disproportion between the uptake of iodide and the iodide organification may result in the increase in unbound iodide. It is concluded that the hypothyroidism in Hashimoto's disease may not be caused by a defect in iodide organification, even if it correlated to the degree of hypothyroidism.
EFFECTS OF EXPERIMENTAL HYPOTHYROIDISM ON SKELETAL MUSCLE METABOLISM IN THE RAT
Authors: van Hardeveld C. , Kassenaar A. A. H.
Published: December 2008

Hind-limb perfusion was used to study the effect of thyroidectomy on some metabolic parameters in the skeletal muscle of the rat. A week after thyroidectomy obtained by one dose of 3/4 mCi 131I, neither T4 nor T3 was detected in the blood. Lactate production and glycerol production were already decreased a week after the treatment and reached a base level at two weeks. At that time, the oxygen consumption was significantly lower (70 % of initial level) than in the control animals and decreased further in the third week to nearly 50 % of the control level.

Glucose consumption and alanine release were decreased three weeks after thyroidectomy. One dose of T3 (10 μg/100 g b. w.), administered to animals two weeks after the injection of 131I, restored the oxygen consumption, lactate production, and glycerol production to normal levels in 24 h. After 48 h, the glucose consumption was normal. Glycerol production was already significantly increased 6 h after T3 injection in animals one week after thyroidectomy, and in another group of animals two weeks after thyroidectomy. Apparently the diminished oxygen consumption in the latter group does not retard the lipolytic response to T3. No direct relationship could be found between the activity of lipolytic process and the thyroid hormone controlled oxygen consumption.
THE EFFECT OF URINARY GLUCOSE EXCRETION ON THE PLASMA GLUCOSE CLEARANCES AND PLASMA INSULIN RESPONSES TO INTRAVENOUS GLUCOSE LOADS IN UNANAESTHESIZED DOGS
Authors: Kaneko J. J. , Mattheeuws D. , Rottiers R. P. , Van Der Stock J. , Vermeulen A.
Published: December 2008

The effect of urinary glucose excretion on the plasma glucose clearance and insulin response to varying sizes of glucose loads was studied in normal unanaesthesized dogs. Glucose loads ranging from 0.15 to 1.25 g/kg b.w. were infused intravenously in a standard time period of 30 seconds. Plasma glucose and plasma immunoreactive insulin (IRI) concentrations were determined during one-hour after infusion. All urine excreted during the one-hour was collected by a catheterization and bladder wash-out procedure. The urinary glucose excretion was expressed as the percent of the glucose load. The urinary glucose excretion varied directly with the size of the glucose load and ranged from minimal to 12 %. This would indicate that urinary losses play a considerable role proportionate to the degree of hyperglycaemia above the renal threshold. Thus, urinary loss of glucose must be recognized as an important factor influencing the plasma glucose clearance and hence the plasma IRI response. A glucose load of 0.5 g/kg b.w. given in 30 seconds with the k-value calculated between 15–45 min would minimize the influence of urinary loss and provide more accurate plasma clearance values.