bluuebunny/crossref_metadata_2025 huggingface dataset:
INFLUENCE OF GROWTH HORMONE ON SPLANCHNIC GLUCOSE PRODUCTION IN MAN
Authors: Adamson Ulf , Wahren John , Cerasi Erol
Published: December 2008

The influence of growth hormone (GH) on splanchnic exchange of glucose and glucogenic precursors was investigated in 11 healthy subjects using the hepatic venous catheter technique. GH was infused intravenously at the rate of 40 μg/kg body weight over 30 min. A peak plasma GH level of 219 ± 25 ng/ml was obtained. During GH infusion the blood glucose concentration fell slightly but significantly. In addition, the splanchnic glucose output decreased by approximately 35–40% during and immediately after GH infusion. The splanchnic uptake of the glucogenic precursors lactate, pyruvate, alanine and glycerol was not significantly influenced by GH infusion. The arterial concentration of insulin fell slightly, while the glucagon level remained unchanged during the infusion but decreased 20–30 min after the end of GH infusion. Indirect estimates of the peripheral glucose utilization indicated that GH infusion was accompanied by a 25% reduction in peripheral glucose uptake.

The influence of GH on the inhibition of splanchnic glucose output induced by endogenous insulin in connection with intravenous glucose infusion (2 mg/kg/min) was studied in 6 subjects. GH infusion, given 60 min before the onset of glucose administration, did not significantly modify the splanchnic glucose output response to glucose infusion.

It is concluded that a) GH may exert a direct inhibitory influence on splanchnic glucose output which is independent of changes in insulin and glucagon, b) hepatic glycogenolysis, but probably not gluconeogenesis is influenced by GH, and c) GH infusion is accompanied by decreased peripheral utilization of glucose.
SIMULTANEOUS DETERMINATION OF THE CONTENT OF SEROTONIN, DOPAMINE, NORADRENALINE AND ADRENALINE IN PANCREATIC ISLETS ISOLATED FROM FED AND STARVED MICE
Authors: Hansen S. E. , Hedeskov C. J.
Published: December 2008

A highly sensitive double isotope method for the simultaneous determination of serotonin, dopamine, noradrenaline and adrenaline has been developed. Advantages and limitations of the method are discussed.

The mentioned biogenic amines are all present in isolated pancreatic islet tissue from albino mice in concentrations ranging from approximately 5-30 μmol per kg wet weight (0.8–5 × 10−3 pmol/ng DNA). A somewhat higher content of these amines, especially dopamine, was found in pancreatic acinar tissue.

The hypothesis that the impaired glucose-induced insulin secretion during starvation partly is caused by an increased content of biogenic amines in the pancreatic islets was not supported by our experiments which showed an unchanged islet content of these amines after 48 h starvation.
AN IN VIVO MODEL FOR TESTING INHIBITION OF ARGININE-INDUCED INSULIN AND GLUCAGON RELEASE BY SOMATOSTATIN ANALOGS
Authors: Gordin Ariel , Meyers Chester , Arimura Akira , Coy David H. , Schally Andrew V.
Published: December 2008

An animal model for testing the in vivo potency of somatostatin analogs in inhibiting the release of insulin and glucagon is described. The secretion of these pancreatic hormones was stimulated in rat by infusion of arginine. The plasma insulin level increased almost to a maximum after an infusion of 10 min, while plasma glucagon rose more slowly, reaching its maximum only after a 30 min infusion. Concomitant infusion of graded doses of somatostatin (2.5, 10, 40 and 160 μg/100 g BW) for 30 min inhibited both insulin and glucagon release in a dose-dependent manner, enabling us to test somatostatin analogs for insulin and glucagon-suppressive activity in a semi-quantitative manner. Using this animal model, 3 analogs of somatostatin, [D-Cys14]-, [Ala2, D-Cys14]- and [D-Trp8, D-Cys14]somatostatin were tested in a 4-point assay. They all showed dissociated activity in inhibiting the secretion of glucagon more than that of insulin.
SPECIES DIFFERENCES IN STEROIDOGENESIS FOLLOWING THE IN VITRO INCUBATION OF DECAPSULATED TESTES
Authors: de la Torre B. , Hedman M. , Diczfalusy E.
Published: December 2008

Decapsulated testes of rats, guinea pigs and rabbits were incubated with or without labelled precursors and the steroids formed under various experimental conditions were analysed. Also a decapsulated human testis was incubated with labelled acetate.

Cholesterol, testosterone and androstenedione were isolated in a radiochemically homogeneous form following the incubation of carbon-14-labelled sodium acetate with decapsulated testes of all 3 animal species. No other labelled steroid was detected following the incubation of rat testes. Guinea pig testes also converted labelled acetate to pregnenolone. Rabbit and human testes converted labelled acetate to cholesterol, pregnenolone, dehydroepiandrosterone, androstenediol, testosterone and androstenedione. When decapsulated testes of rats, guinea pigs and rabbits were incubated with carbon-14 labelled pregnenolone as a precursor, radiochemically homogeneous progesterone, 17-hydroxypregnenolone, dehydroepiandroster-one, androstenediol, androstenedione and testosterone were isolated in each experiment.

Using radioimmunoassay techniques, preformed steroids together with steroids formed from endogenous precursors were analysed following the incubation of rat, guinea pig and rabbit testes in the absence and in the presence of human chorionic gonadotrophin (HCG).

Marked (seasonal?) variations were observed between the results of experiments conducted at different times. Incubation of guinea pig testes in the absence as well as in the presence of HCG resulted in a major increase in pregnenolone levels. No such finding was encountered when rat and rabbit testes were incubated. The addition of HCG resulted in at least a 10-fold increase in testosterone formation by the testes of all three species. The addition of HCG to the incubation medium induced a marked rise in dihydrotestosterone levels in the rabbit testes but had no effect whatsoever on the levels of this steroid in guinea pig testes.

It is concluded that considerable species differences exist in the steroid metabolism of decapsulated testes incubated in vitro.
THE EFFECTS OF THE DOPAMINE AGONIST, LERGOTRILE MESYLATE, ON PROLACTIN SECRETION IN WOMEN
Authors: Leebaw Wayne , Lee Louyse , Woolf Paul
Published: December 2008

Lergotrile mesylate, an ergot derivative and dopamine agonist, decreases basal (single sample) prolactin levels and blunts phenothiazine-mediated prolactin release. To more thoroughly evaluate the effect of this drug, we measured prolactin and growth hormone concentrations hourly over 24 h in 5 healthy women and during insulin (0.1 U/kg) induced hypoglycaemia (ITT) in 6 women before and during 2-day lergotrile treatment. Lergotrile (4.0 to 6.0 mg/day) significantly decreased the mean 24-hour prolactin concentration in 3 and abolished the nocturnal rise in 4. For the entire group, the mean nocturnal levels (2400–0700 hours) were 24.0 #x00B1;7.5 vs 14.4 ± 3.9 ng/ml during waking (0800–2300 hours) pre-lergotrile (P<0.05), while during therapy the concentrations were 8.9 ± 2.8 vs 8.0 ± 1.4 ng/ml (NS), respectively. The prolactin response to ITT was also significantly inhibited by lergotrile with the peak response reduced from 78.2 ± 35.1 ng/ml to 9.0 ± 3.6 ng/ml (P < 0.05). The mean 24-hour growth hormone concentration was unchanged during therapy, and there was no significant effect on the GH response during ITT.

The effects of chronic therapy with lergotrile (8 mg/day for 6 weeks) were studied in one acromegalic patient with elevated levels of prolactin and growth hormone. Her prolactin concentration fell from 452.2 ± 8.0 to 216 ng/ml, while GH declined from 23.8 ± 1.3 to 14.8 ng/ml.

Lergotrile mesylate effectively lowers mean 24-hour prolactin concentrations (determined hourly) and completely abolishes both nocturnal and hypoglycaemia-mediated prolactin release. This drug may also be beneficial in the therapy of acromegaly.
DOSE-RESPONSE STUDY WITH A NEW LH-RH ANALOGUE, D-Ser (TBU)6 LH-RH 1–9 (EA)10 DURING THE FOLLICULAR PHASE OF THE MENSTRUAL CYCLE
Authors: Friedrich E. , Etzrodt A. , Becker H. , Hanker J. P. , Keller E. , Kleisl P. , Pinto V. , Schindler A. E. , Schneider H. P. G. , Vanderbeke O. , Werder H. , Wyss H. I.
Published: December 2008

D-Ser (TBU)6 LH-RH 1–9 (EA)10 (HOE 766) a highly active LH-RH analogue, was studied with regard to its effects on the release of follicle stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol-17β (Oe2) during the follicular phase of the menstrual cycle. Forty-two regularly menstruating women were allowed to five different treatment groups with different doses (1.25 μg; 2.5 μg; 5.0 μg; 10.0 μg; 20.0 μg) of HOE 766 given as intravenous bolus injections and the plasma concentrations of FSH, LH and Oe2 were measured up to 24 h after injection using specific radioimmunoassays. In the majority of cases, peak values of both FSH and LH occurred 4 h after injection being significantly different from pre-injection levels (P < 0.02 in the 1.25 μg treatment group, P < 0.005 for the other treatment groups). Statistical analysis of maximum values as well as the absolute and relative increase in the different treatment groups revealed a dose-dependent effect of HOE 766.

Maximum values of Oe2 occurred 8 h after injection and were found to be significantly different from pre-injection levels (P < 0.005). However, no dose dependent effect was observed. It was concluded that HOE 766 is a potent and long-acting stimulator of FSH, LH and Oe2 release in women. The effect of HOE 766 is dose dependent for FSH and LH but not for Oe2.
EFFECT OF TSH ON cAMP AND cGMP LEVELS IN THYROID CANCERS, ADENOMAS AND NORMAL HUMAN THYROID TISSUE
Authors: Thomas-Morvan Colette
Published: December 2008

The effect of TSH (50 mU/ml) alone or in combination with theophylline (10 mm) on the cAMP level in human thyroid tissue after a 10 min incubation has been studied in 8 normal tissues, 7 adenomas and 10 thyroid cancers (8 differentiated and 1 anaplastic). Our results have shown the lack of responsiveness to TSH in the 2 anaplastic carcinomas studied, as well as in 4 cases among the 8 differentiated cancers studied. In thyroid adenomas, on the contrary, the cAMP increase in response to TSH was close to that observed in normal tissues. In these adenomas, the mean basal cAMP level (0.43 ± 0.07 pmol/mg tissue) was not statistically different from that in normal tissues (0.36 ± 0.06), while in thyroid cancers the mean basal cAMP level (0.93 ± 0.26) was significantly greater than that in normal tissues (P < 0.05).

The cGMP level was measured in the same conditions in 7 normal thyroid tissues and 8 thyroid cancers (7 differentiated and 1 anaplastic). The mean basal cGMP level in these cancers (9 ± 1 fmol/mg tissue) was not statistically different from that in normal tissues (12 ± 2). In response to TSH, no increase of cGMP level was observed in cancers, or in the normal tissues.

The disorders of hormone synthesis previously seen in human thyroid cancers did not appear related to a decreased cAMP content, but might be due to a lack of responsiveness to TSH in undifferentiated cancers and in some cases of differentiated carcinomas.
COMPARISON OF THE METHODS FOR TISSUE TRIIODOTHYRONINE (T3) EXTRACTION AND SUBSEQUENT RADIOIMMUNOASSAY
Authors: Takaishi Masaru , Miyachi Yoshie , Aoki Mariko , Shishiba Yoshimasa
Published: December 2008

Although there have been various reports on tissue T3 concentration, the examination of the quality of radioimmunoassay has not been available. In the present study, we tried to determine whether the available methods for T3 extraction are adequate for the various methods of T3 radioimmunoassays used. T3 was extracted from liver by ethanol extraction or by acid butanol extraction (Flock's method) and the extract was applied to radioimmunoassay either by Seralute T3 column, ANS-double antibody or the ANS-charcoal method. The values of T3 were compared with those obtained by isotope-equilibration method. The dilution curve of ethanol extract was not parallel with that of the standard in ANS-charcoal or ANS-double antibody technique. When the extract was tested by Seralute method, the dilution curve was parallel to the standard, whereas the T3 value obtained with this method was two-fold higher than that with the isotope equilibration technique. The analysis of the ethanol extract suggested that the lipid extracted by ethanol interfered with the assay. The acid butanol extract when tested either by the ANS-double antibody or Seralute method, showed parallelism to the standard curve and gave T3 values almost identical with those by the isotope-equilibration method. When tested by ANS-charcoal method, the dilution curve of the acid butanol extract was not parallel to the standard. Thus, to obtain reliable results, tissue extraction by Flock's method and subsequent T3 radioimmunoassay by either ANS-double antibody or Seralute T3 method are recommended.
FAMILIAL CUSHING'S SYNDROME
Authors: Arce Bartolomé , Licea Manuel , Hung Santiago , Padrón Rubén
Published: December 2008

Cushing's syndrome has been demonstrated in four of seven siblings with clinical manifestations appearing around puberty in three of the four siblings. The only other associated findings in these cases were short stature and disturbed carbohydrate metabolism. Adenomatous hyperplasia of the adrenal glands was demonstrated in 3 of the patients, and a virilizing adrenal carcinoma in the fourth sibling. The pathogenesis of the adrenocortical disorders in these siblings is discussed.
CONGENITAL ADRENAL HYPERPLASIA: SIMULTANEOUS DETERMINATION OF PLASMA ALDOSTERONE AND 17-HYDROXYPROGESTERONE
Authors: Parth K. , Zimprich H. , Swoboda W. , Brunel Roswitha , Bohrn Edith
Published: December 2008

Plasma levels of aldosterne and 17-hydroxyprogesterone were determined in 5 just diagnosed cases of congenital adrenal hyperplasia due to 21-hydroxylase deficiency without salt-loss before onset of therapy, and in 14 children suffering from the same disorder, under glucocorticoid therapy before and after withdrawal of therapy for one week as well as before and after ACTH-stimulation. Furthermore, urinary pregnanetriol, pregnanetriolone, 17-ketosteroids and 17-ketogenic steroids were determined with and without therapy. Serum concentrations of 17-hydroxyprogesterone in patients before onset of therapy were at least 40 times above the normal range (normal range: 0.39 ± 0.23 ng/ml determined in 19 children of age 1–12 years), aldosterone was also elevated (range 16.5–84.4 ng/100 ml, normal aldosterone being 7.3 ± 4.7 ng/ml). In contrast, well controlled patients (judged on urinary pregnanetriol-excretion) had normal aldosterone (one exception) and 17-hydroxyprogesterone levels below 5 ng/ml. Both steroids were well stimulated by ACTH. In 3 poorly controlled cases elevated pregnanetriol and 17-hydroxyprogesterone values up to 130.9 ng/ml were found. Withdrawal of therapy resulted in pronounced rise of aldosterone and 17-hydroxyprogesterone. Exogenous ACTH had no detectable effect in 7 cases leading to further stimulation in the other children. We found an excellent correlation between plasma 17-hydroxyprogesterone and urinary pregnanetriol (r = 0.84, P < 0.003, n = 14). Fairly good correlation also exists between aldosterone and 17-hydroxyprogesterone values (r = 0.65, P < 0.01, n = 14) in patients before the onset and after withdrawal of therapy.

The data confirm the value of 17-hydroxyprogesterone determinations for diagnosis and management of congenital adrenal hyperplasia on the one hand, and the compensatory elevated aldosterone production in the non-salt-losing form of the disorder on the other.
EFFECT OF AMINOGLUTETHIMIDE PHOSPHATE ON IN VITRO OESTRADIOL STIMULATED PROGESTERONE SYNTHESIS BY RABBIT CORPORA LUTEA
Authors: Fuller Gene B. , Markaverich Barry M. , Hobson William C.
Published: December 2008

Slices of rabbit corpora lutea were incubated for 3 and 8 h with oestradiol-17β in the presence or absence of aminoglutethimide phosphate (AGP)2) in order to identify a possible site(s) of action of oestrogen on progesterone synthesis. Oestradiol was unable to increase progesterone biosynthesis above controls in luteal tissue exposed to AGP during either incubation period. AGP alone significantly reduced progesterone concentrations and synthesis from [14C]acetate at both time periods while oestradiol alone increased progesterone mass at 8 h. Changes in 20α-OH progesterone typically paralleled those of progesterone at 3 h but no effect of the inhibitor was seen at 8 h. Except for an increase in 14C-incorporation into cholesterol esters in the AGP-treated groups at 3 h the concentration or synthesis of sterols from labelled acetate did not respond to treatment.

These results suggested that cholesterol side chain cleavage and cholesterol synthesis are not major in vitro sites of action of oestradiol in the rabbit corpus luteum.
IN VIVO INTERACTION BETWEEN STEROIDAL ALKYLATING AGENTS AND OESTROGEN RECEPTORS IN RABBIT UTERI
Authors: Asai Masafusa , Takeuchi Hiroshi , Okada Hiroji
Published: December 2008

The binding of steroidal alkylating agents to specific tissue component is necessary for the selective distribution of these compounds to their target tissues. The in vivo interaction of Estracyt or NSC-112259 with oestrogen receptors may play an important role in their action mechanism.

Both Estracyt and NSC-112259 which were administrated in vivo, gradually reduced the binding of [3H]oestradiol to cytoplasmic oestrogen receptor in rabbit uteri. From this, it was suggested that a negligible amount of oestradiol was released from these compounds and that the oestradiol moiety was useful as a carrier for the nitrogen mustard moiety. And it appeared that the synthesis of a new receptor protein was inhibited by the nitrogen mustard moiety, thereby causing a decrease in the cytoplasmic oestrogen receptor level.
CORD SERUM PROLACTIN IN RELATION TO THE TIME OF THE DAY, THE SEX OF THE NEONATE AND THE BIRTH WEIGHT
Authors: Badawi M. , Van Exter C. , Delogne-Desnoeck J. , Van Meenen F. , Robyn C.
Published: December 2008

Serum prolactin was measured in 581 blood samples collected immediately after birth from 563 single new-born and from 9 pairs of twins.

Cord serum prolactin is high at birth: the mean level is some 5 times higher than in adults. There is no sex difference in cord serum prolactin concentration in the neonate.

Mean serum prolactin is significantly higher at 1.00 and 2.00 a.m. Thus a circadian periodicity in serum prolactin concentration seems to appear already during foetal life well before the organization of sleep rhythm.

Cord serum prolactin increases with birth weight ranging from 1500 g to 3500 g. Thus, the control of levels of circulating prolactin changes during foetal life resulting in a progressive increase starting from mid-pregnancy.

Mean cord serum prolactin at birth is lower in twins than in single newborns. There is no significant difference in serum prolactin between the first and the second twin.
ABSENCE OF POSITIVE FEEDBACK EFFECT OF OESTROGEN ON LH RELEASE IN PATIENTS WITH TESTICULAR FEMINIZATION SYNDROME
Authors: Aono Toshihiro , Miyake Akira , Kinugasa Takayuki , Kurachi Keiichi , Matsumoto Keishi
Published: December 2008

The response of serum LH to exogenous oestrogen administration was studied in 5 patients with testicular feminization syndrome (TFS).

The serum LH levels were elevated in all the patients, while serum testosterone levels were within the normal male range. Serum FSH levels were elevated in 4 patients and normal in one patient. Intravenous administration of 100 μg of LH-RH provoked a further increase in both LH and FSH. Following intravenous injection of 20 mg of conjugated oestrogen (Premarin®), the LH levels were serially determined until 120 h in TFS patients, 5 normal males, and 10 normal females during the mid-follocular phase (D7-9). Both TFS patients and normal males showed no LH release following oestrogen injection in contrast to normal females who displayed a significant increase in LH with a peak at 48 to 56 h after the injection.

These results seem to suggest that the insensitivity of the hypothalamus to androgen in TFS patients do not affect the sex differentiation of the hypothalamus. The possible role of oestradiol conversion from testosterone in the hypothalamus is discussed.
CHANGES IN SERUM TSH LEVEL AFTER INTRAVENTRICULAR INJECTION OF VARIOUS NEUROMEDIATORS IN RATS
Authors: Holak Henryk , Baldys Agata , Jarzab Barbara , Wystrychowski Antoni , Skrzypek Jan
Published: December 2008

The influence of various neuromediators on pituitary TSH secretion in rats has been investigated. Noradrenaline 50 μg/rat, dopamine 50 μg/rat, serotonine-creatinine-sulphate 100 μg/rat, gamma-aminobutyric acid 100 μg/rat, pilocarpine 1 mg/rat, histamine 100 μ/rat were administered into the lateral ventricle of the brain. All agents were dissolved in Parker's fluid. Two control groups of animals were given Parker's fluid and subjected to surgical manipulations, respectively. Plasma TSH level was estimated after 30 min by means of radioimmunoassay.

The increase in the TSH level was observed after the injection of serotonine and noradrenaline (4.0 and 3.1 ng/ml, respectively) as compared with control group (0.7 ng/ml).
RADIOIMMUNOASSAY OF 3,3′,5′-TRIIODOTHYRONINE (REVERSE T3) ON SMALL REUSABLE SEPHADEX COLUMNS
Authors: Faber Jens , Friis Thorkild , Kirkegaard Carsten , Siersbæk-Nielsen Kaj
Published: December 2008

A simple radioimmunoassay for serum reverse triiodothyronine on small reusable Sephadex G 25 fine columns has been developed. The assay was unaffected by serum volumes of up to 100 μl. The recovery of reverse T3 added to serum was in the mean 98.3 ± sem 3.2 % and the coefficient of variation within and between assay determinations 5.4 % and 7.5 %, respectively. The detection limit was 2.2 pg reverse T3/column. Serum reverse T3 in 58 euthyroid controls was in mean 48 ± sd 9 ng/100 ml, and was positively correlated to age (P < 0.001). No overlap was found between the control group, and the hypo- and hyperthyroid group respectively. Three patients with T3-toxicosis had a normal serum rT3.
IODOAMINO ACID COMPOSITION OF POORLY IODINATED HUMAN THYROGLOBULIN FRACTIONATED BY ISOPYCNIC CENTRIFUGATION
Authors: Vignal A. , Nataf B. M. , Tubiana M.
Published: December 2008

The distribution of iodotyrosines and iodothyronines has been studied in poorly iodinated 19 S thyroglobulins isolated by sucrose gradient centrifugation from five human thyroid tissue. The 19 S thyroglobulins have been fractionated by isopycnic centrifugation in 34.5 % rubidium chloride gradient. The distribution of iodoamino acids depends on the total iodine content of each fraction. The variations in MIT1) and DIT residues with increasing levels of iodination are not identical, the elevation of DIT residues being higher than that of MIT. The number of T4 residues increases quite rapidly after 5 atoms of iodine while T3 increases slightly and slowly. It is shown here that, even after fractionation of poorly iodinated thyroglobulin, the synthesis of thyroid hormones is observed at a level of iodine content as low as 1.4 and 1.8 atoms per molecule of thyroglobulin. This shows that the thyroglobulin fractions obtained by isopycnic centrifugation are still heterogeneous, although less than the initial non-fractionated thyroglobulin. In order to explain our data, it must be admitted that a large proportion of thyroglobulin molecules are not iodinated.
INHIBITION OF ANGIOTENSIN III ACTION BY DES-ASP1-,ILEU8-ANGIOTENSIN II IN MAN
Authors: Kono Tsuyoshi , Ikeda Fumitake , Oseko Fumimaro , Nanno Masataka , Imura Hiroo , Endo Jiro
Published: December 2008

In 5 normal men intravenous infusion of 600 ng/kg/min of des-asp1-,ileu8-angiotensin II (AIIIA) inhibited a rise in blood pressure as well as increase in plasma aldosterone caused by an intravenous infusion of 20 or 100 ng/kg/min of des-asp1-angiotensin II (angiotensin III, AIII). This result and our previous study on simultaneous infusions of 600 ng/kg/min of AIIIA and 20 ng/kg/min of angiotensin II (All) in the same 5 normal men demonstrate that this dose of AIIIA antagonizes AIII and All on the adrenal cortex as well as peripheral arterioles and that AIIIA has the same degree of inhibitory effect on the aldosterone-stimulating action of AIII and on that of All in man.
THE EFFECT OF LOCAL TESTICULAR IRRADIATION ON TESTICULAR HISTOLOGY AND PLASMA HORMONE LEVELS IN THE MALE RAT
Authors: Hopkinson C. R. N. , Dulisch B. , Gauss G. , Hilscher W. , Hirschhäuser C.
Published: December 2008

Adult male rats were subjected to local testicular irradiation, plasma hormone levels and testicular histology being quantified at intervals up to 52 days thereafter.

LH and FSH increased coincidently with spermatid but not with spermatocyte or spermatogonia depletion. Testosterone levels seemed to decrease but this effect was not significant. Oestradiol levels showed no significant changes.

From the correlations between the various parameters it was concluded that the lack of inhibin was the main cause of the increase in both LH and FSH and that spermatids provide the signal for production of this non-steroidal inhibitor. The site of inhibin production was not definitively established but the results would be consistent with production of inhibin by the Sertoli cells in association with spermatids.
KININASE INHIBITION BY GLUCAGON
Authors: Olsen Uffe Bang
Published: December 2008

In vitro glucagon (1–100 μg/ml) has been shown to inhibit the degradation of bradykinin by kininases present in kidney microsomes and erythrocytes. Glucagon was less active on kininases present in plasma and was inactive on purified pancreatic carboxypeptidase B. In conscious dogs the intravenous infusion of glucagon (10 μg/min) increased urine flow (160 %) and urine kinin excretion (130%) and decreased urine kallikrein excretion (14 %). It is suggested that in vivo inhibition of kininases might contribute to the biological effects of glucagon.
EFFECT OF PROSTAGLANDIN SYNTHETASE INHIBITORS ON RENIN AND ALDOSTERONE IN MAN ON A NORMAL OR LOW SODIUM DIET
Authors: Norbiato G. , Bevilacqua M. , Raggi U. , Micossi P. , Moroni C. , Fasoli A.
Published: December 2008

The effect of two inhibitors of prostaglandin synthetase activity (acetylsalicylic acid (ASA) and diclofenac sodium (DCFS)) on plasma renin activity (PRA) and plasma aldosterone (PA) was studied in normal subjects kept on a diet with constant sodium and potassium intake or on a low-salt diet for 7 days.

In 9 subjects, 2 days of treatment with ASA (3 g/day) was followed by a significant decrease of PA in the supine position (after overnight rest); there was no significant decrease of PRA. However, both PA and PRA with the subjects in the upright position were significantly reduced after ASA.

In 9 subjects treated with DCFS (200 mg for 2 days), both PA and PRA with the subjects in the supine and upright positions decreased significantly. Similar results were obtained from 4 subjects on a low-sodium diet (15–30 mEq./day) treated with DCFS (150 mg/day for 3 days).

In contrast, no significant changes in PA or PRA with the subjects in the supine or upright position were observed in 4 subjects on a very low sodium diet (< 15 mEq./day) treated with DCFS (150 mg/day for 3 days). Covariance analysis (with PRA as independent variable and PA as dependent variable) of the data obtained in the upright position before and after treatment with ASA or DCFS showed that the decrease in PA remained significant after adjustment for the PRA effect.

These results suggest a direct effect of prostaglandins on PA. The data obtained from subjects on a low sodium diet indicate that sodium deprivation may counteract the effects of DCFS on PRA and PA.
THE SEQUENCE OF HORMONAL CHANGES DURING PROSTAGLANDIN INDUCED LUTEOLYSIS OF THE SUPERLUTEINIZED RAT OVARY
Authors: Torjesen P. A. , Dahlin R. , Haug E. , Aakvaag A.
Published: December 2008

Immature female rats were pre-treated with pregnant mare's serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) to achieve superluteinization. Eight days after the HCG administration luteolysis was induced by sc injection of 5 μg of the prostaglandin F2α (PGF2α) analogue cloprostenol (Estrumate®). The serum levels of progesterone, 20α-dihydroprogesterone (20α-DHP), prolactin (PRL) and luteinizing hormone (LH) as well as the number of ovarian LH binding sites were measured during the first 23 h after cloprostenol injection.

The serum levels of progesterone decreased from 500 to 200 ng/ml within 25 min after cloprostenol administration. A further decrease to 20 ng/ml occurred during the next 4 h, and serum progesterone remained low for the rest of the period. An increase in serum prolactin (PRL) to values between 28 and 44 ng/ml was observed after 3 h and the values remained elevated for the next 7 h. Although the serum levels of progesterone declined immediately, the serum 20α-dihydroprogesterone (20α-DHP) levels remained at 60 to 140 ng/ml for the first 5 h and then gradually increased to values corresponding to the initial progesterone levels 14 to 23 h after treatment. The number of ovarian LH binding sites was between 1.2 and 1.4 × 10−12 mol/mg protein during the first 9 h after prostaglandin (PG) injection, and then decrreased to 0.8 and 0.5 × 10−12 mol/mg protein at 14 and 23 h, respectively. The serum LH levels remained below the limit of detection for the assay (10 ng/ml) throughout the observation period. PGF2α injection induced the same basic changes in the serum levels of progesterone and 20α-DHP as cloprostenol treatment.

Thus, the first effect of PG treatment measured was an immediate decline in the serum levels of progesterone, and this decline probably initiated the subsequent increase in pituitay PRL and ovarian 20α-DHP secretion. Therefore, the decrease in the number of ovarian LH binding sites appeared to be a consequence rather than a mediator of luteolytic effects of the prostaglandins.
SERUM LEVELS OF TESTICULAR AND ADRENAL STEROIDS AFTER DEXAMETHASONE AND HCG-ADMINISTRATION IN THE LABORATORY-MAINTAINED RHESUS MONKEY
Authors: Wickings E. J. , Nieschlag E.
Published: December 2008

In order to evaluate the endocrine testicular and adrenal function of rhesus monkeys in vivo, and to compare this with the human situation, the effect of dexamethasone (Dxm), HCG and combined Dxm/HCG administration on the steroid levels was investigated in 8 adult male rhesus monkeys in November/December (= season of high testicular activity). Serum levels of cortisol, testosterone (T), androstenedione (A), 17-hydroxyprogesterone (17-OHP), oestradiol (Oe2), dehydroepiandrosterone (DHA) and its sulphate (DHA-S) were measured radioimmunologically.

Basal T and DHA serum levels were similar to those found in man, whilst A levels amounted to 1/10 and DHA-S to 1/30 of human values. Oe2 and 17-OHP levels were higher than in man. T and A levels were not suppressed by Dxm and very high degrees of stimulation were reached after HCG. The HCG-induced increment in T was smaller under Dxm/HCG than under HCG alone. 17-OHP levels were reduced to 25% of basal levels under Dxm, but the incremental response to Dxm/HCG was the same as that without Dxm. DHA and DHA-S were 60 and 75% lower under Dxm, and the increment in DHA after Dxm/HCG was less than that after HCG. DHA-S did not respond to HCG.

In conclusion, several important differences in basal steroid levels and in the response to dynamic testing were found in the rhesus monkey, as compared to man. The adrenal contributes 75% to circulating 17-OHP levels, and 60 and 75% respectively to DHA and DHA-S levels. A is produced solely by the testis in the rhesus monkey. As compared to man, the rhesus monkey testis in vivo synthesises T via both the Δ4 and Δ5 pathways. The Δ5 pathway appears to be dependent on adrenal steroid precursors.
EFFECT OF INSULIN INDUCED HYPOGLYCAEMIA ON THE BLOOD LEVELS OF CATECHOLAMINES, GLUCAGON, GROWTH HORMONE, CORTISOL, C-PEPTIDE AND PROINSULIN BEFORE AND DURING MEDICATION WITH THE CARDIOSELECTIVE BETA-RECEPTOR BLOCKING AGENT METOPROLOL IN MAN
Authors: Hökfelt Bernt , Hansson Bengt-Göran , Heding Lise G. , Nilsson Karl Olof
Published: December 2008

Studies were performed in 8 males with moderate hypertension to explore the influence of metoprolol on the sensitivity to insulin and on the response to hypoglycaemia with respect to plasma catecholamines, glucagon, growth hormone and cortisol. C-peptide and proinsulin were determined in some instances. All subjects were studied before treatment, after one month on placebo and after 3 months on metoprolol. The final maximal dose used was 50–150 mg three times daily.

The sensitivity to insulin was the same during all three conditions studied. The response in catecholamines, glucagon, growth hormone and cortisol following insulin induced hypoglycaemia was similar during placebo as compared to no treatment.

Adrenaline, growth hormone and cortisol showed a greater response to hypoglycaemia during metoprolol whereas no difference was seen with respect to noradrenaline and glucagon.

The half-life of exogenous insulin was the same before and during metoprolol (7.6 min).

Metoprolol caused no changes in the basal C-peptide levels. During the hypoglycaemic phase C-peptide showed a continuous gradual fall, which was similar before and during metoprolol. Proinsulin was below the lower limit of detection before and following the injection of insulin both without treatment and during metoprolol.
INHIBITION OF TESTOSTERONE 5α-REDUCTASE BY AND ANTIANDROGENICITY OF ALLENIC 3-KETO-5,10-SECOSTEROIDS
Authors: Voigt Walter , Castro Albert , Covey Douglas F. , Robinson C. H.
Published: December 2008

(4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione(II), a 3-keto-5,10-secosteroid which is an irreversible inhibitor of Δ5-3-ketosteroid isomerase was tested for its possible antiandrogenicity in the hamster flank organ test. The organs of female animals topically treated with 4 μg of testosterone propionate (TP) for 4 weeks enlarged in size and showed pigmentation resembling adult males. When compound II was applied concomitantly with TP, androgenic stimulation was completely blocked and the flank organs remained small like those of female animals. These results suggest that compound II may be a useful anti-androgen when applied topically. It may well act mainly by inhibition of the formation of 5α-reduced metabolites of testosterone, as judged by its effect on rat prostatic 5α-reductase. Thus, incubation of a rat prostatic homogenate with [4-14C]testosterone produced 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol as the main products. However, when compound II was included in the incubation mixture, the production of these 5α-reduced metabolites was markedly inhibited.
THYROID HORMONE FORMATION IN ECTOPIC THYROID GLAND
Authors: Matsumoto Toshio , Ogata Etsuro , Yamamoto Michiko , Aiyoshi Yuji , Nagataki Shigenobu
Published: December 2008

Several steps of thyroid hormogenesis were studied on a subhyoid ectopic thyroid tissue in a case of compensated hypothyroidism with simultaneous sublingual and subhyoid ectopic thyroid.

The patient, a 19-year-old girl, had normal values for serum T4, T3U and T3, and an elevated serum TSH level. The thyroidal 131I uptake was elevated both at 3 h and 24 h after oral 131I intake. No significant discharge of radioiodine was observed after perchlorate load. On the thyroid biopsy specimen, peroxidase activity was shown to be normal by both assays of guaiacol oxidizing and iodinating activity. Thyroglobulin was 19S and was normally iodinated in vitro with peroxidase. Iodine content of thyroglobulin was within the normal range. The mean percentage distribution of 131I administered 7 days prior to the biopsy showed no significant difference from the normal pattern.

From these studies, no specific defects in thyroid hormogenesis could be detected in this case. It is suggested that abnormalities in thyroid function in this case are mainly due to insufficient functioning mass in the ectopic thyroid.
EFFECT OF ANTITHYROID TREATMENT ON CALCIUM-PHOSPHORUS METABOLISM IN HYPERTHYROIDISM
Authors: Mosekilde Leif , Melsen Flemming
Published: December 2008

Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.
QUALITATIVE AND SEMIQUANTITATIVE CALCIUM CYTOCHEMISTRY IN B CELLS OF MICE TREATED WITH CYPROHEPTADINE AND MANNOHEPTULOSE
Authors: Klöppel Günter , Bommer Gerhard , Ruttmann Elke , Schäfer Hans-Jörg
Published: December 2008

The effect of cyproheptadine (CPH) and D-mannoheptulose (MH) on the function and the histo- (GBHA-method) and ultracytochemical (pyroantimonate method) calcium handling by pancreatic B cell were studied in mice. Intraperitoneal injection of CPH (45 mg/kg) or MH (1500 mg/kg) produced a hyperglycaemic syndrome, which was accompanied by decreased plasma insulin levels. CPH and MH also abolished glucose-induced insulin release. CPH led to a decrease of about 30 to 40 % in the histochemical calcium content of islets as revealed by semi-quantitative micro-densitometry, while MH did not change the calcium content of the islets. The ultracytochemical distribution pattern of calcium-rich precipitates were identical in CPH and MH treated B cells. The subcellular calcium deposits were predominantly located in the cytoplasmic matrix, but were rarely seen in granule halos and along the cell membranes. In contrast, glucose stimulation of the B cells resulted in an accumulation of the precipitates along the cell membranes and in the secretory granules. The results suggest that CPH and MH inhibit insulin release by either directly or indirectly interfering with the normal calcium handling by the B cell.
SERUM LIPIDS AND LIPOPROTEINS DURING TREATMENT WITH ORAL CONTRACEPTIVES CONTAINING NATURAL AND SYNTHETIC OESTROGENS
Authors: Bostofte E. , Hemmingsen L. , Møller K. J. Alling , Serup J. , Weber T.
Published: December 2008

Increases in serum triglycerides, cholesterol and pre-β- and β-lipoproteins have been considered as significant pathogenic factors regarding the possible thrombotic side-effect of treatment with oral contraceptives of the combined type containing synthetic oestrogen. With the purpose of investigating the influence of natural oestrogen (oestradiol-17β + oestriol/norethisterone acetate) versus synthetic oestrogen (ethinyloestradiol/norethisterone acetate) on serum lipids and lipoproteins in young women compared to independent and individual controls, as controlled double-blind investigation was performed in 33 women in a total material and 18 women in a selected group. The significant changes were as follows: quantitative increases in serum triglycerides (P < 0.001) and β-lipoproteins (P < 0.01) during treatment with synthetic oestrogen, while in contrast no such change was observed in subjects on natural oestrogen, which was found to decrease serum cholesterol (P < 0.05), phospholipids (P < 0.05) and α-lipoprotein (P < 0.05). Quantitative estimation of serum lipoproteins was found to be more valuable than the relative estimation by electrophoresis. It is concluded that oral contraceptives containing natural oestrogens induce less significant and, qualitatively, more benign changes in serum lipids and lipoproteins than preparations containing synthetic oestrogen do.
TREATMENT OF PITUITARY DEPENDENT CUSHING'S SYNDROME WITH CLOSED STEREOTACTIC RADIOSURGERY BY MEANS OF 60Co GAMMA RADIATION
Authors: Thorén M. , Rähn T. , Hall K. , Backlund E. O.
Published: December 2008

Four patients with pituitary dependent Cushing's syndrome were treated with external irradiation to the pituitary using 60Co gamma irradiation given with a stereotactic technique. The size of the sella turcica was normal or slightly enlarged in all patients. The doses given varied between 7000 and 10 000 rad, and the observation time ranged between 14 and 20 months. Three of the patients showed complete clinical remission and one marked improvement. One patient developed ACTH insufficiency, while none developed insufficient secretion of other pituitary hormones. No complications of the irradiation were observed.
INVERSE EFFECTS OF CORTICOSTERONE AND THYROXINE ON GLUCOCORTICOID BINDING SITES IN THE ANTERIOR PITUITARY GLAND
Authors: Koch B. , Lutz-Bucher B. , Briaud B. , Mialhe C.
Published: December 2008

The aim of this study was to determine whether pituitary glucocorticoid binding sites are under hormonal control. It was shown that corticosterone and thyroxine exerted antagonistic effects on both the transcortin-like component and true receptor present in the hypophysis: thyroid hormones, in contrast to glucocorticoids which exhibited opposite influence, increased maximum binding without affecting significantly the apparent association constant. Thus, it seems that the concentration of glucocorticoid binding sites is regulated by the glucocorticoid ligands, as well as by a different hormone. Moreover, a striking parallelism was found between plasma transcortin and pituitary transcortin-like capacity, argueing in favour of a plasma origin for this pituitary binder.
THYROID FUNCTION TESTS IN ADULTS WITH DOWN'S SYNDROME
Authors: Korsager S. , Chatham E. M. , Kristensen H. P. Østergaard
Published: December 2008

Thyroid status was studied in 24 patients above the age of 40 years with Down's syndrome. Three patients had thyroid function tests indicating hypothyroidism. Eight patients had thyroid autoantibodies in serum and 8 patients had a higher than normal level of thyroid stimulating hormone in serum. None of the patients had figures indicating thyrotoxicosis. None of the patients showed any of the clinical signs usually seen in patients with hypothyroidism. It is concluded that biochemical tests indicating hypothyroidism are much more often seen in patients with Down's syndrome than in normal subjects and that thyroid status should be assessed in old patients with this disease.
INTRATHYROIDAL IODINE METABOLISM IN HASHIMOTO'S DISEASE
Authors: Nakashima T. , Inoue K. , Omae T. , Hisatsugu T. , Yoshizumi T.
Published: December 2008

The thyroid of Hashimoto's disease is unique in its susceptibility to exogenous iodide and the positive perchlorate test. It would be of interest to know if there is any alteration of iodine metabolism in the thyroid.

The results obtained in 9 cases with untreated Hashimoto's disease were compared with those in 9 normal thyroids; 5 cases were investigated for iodine metabolism and 4 cases for the peroxidase study.

The thyroglobulin content in thyroid wet weight showed lower values 1.6 ± 1.2 % compared to 8.0 ± 1.5 % in normal. Thyroglobulin represented 18.9 ± 9.3 % of total soluble protein and was significantly lower than normal, 66.9 ± 5.4 %. Iodine content of thyroglobulin was extremely low, 0.10 ± 0.05 % compared to 0.49 ± 0.03% in normal. The thyroglobulin with low degree of iodination showed a low sedimentation coefficient of 18.1 ± 0.1. Distribution of iodo-amino acid-iodine was 8.1 ± 2.8% for thyroxine (T4) and 14.4 ± 9.7 % for triiodothyronine (T3), resulting in a much higher T3/T4 ratio than in normal thyroids. Monoiodotyrosine/diiodotyrosine (MIT/DIT) ratio was higher and T4/DIT ratio was apparently lower than normal. These results resemble the pattern of that found in iodine deficiency. T3/T4 ratio was increased in the blood of patients with Hashimoto's disease. Consequently the alteration of distribution of iodo-amino acids in the thyroid may contribute to the increase in T3/T4 ratio in the blood of this disease.

Peroxidase activity showed 103 ± 51 U/mg particulate protein and was significantly lower than values in normal thyroids, 299 ± 85 U/mg protein.

On the other hand, the total amount of thyroglobulin was not significantly decreased in this disease. The total amount of organified iodine, however, was apparently lower than normal.

These results suggest that the low degree of iodination of thyroglobulin is an essential alteration in the thyroid of Hashimoto's disease.
THE USE OF PROTEOLYTIC ENZYME INHIBITOR (TRASYLOL) IN RADIORECEPTOR ASSAY OF TSH - ITS APPLICATION TO MEASURING THYROID STIMULATING IMMUNOGLOBULINS (TSI) IN THYROID DISEASES
Authors: Kishihara Michizo , Nakao Yoshinobu , Baba Yasuto , Ohgo Shozo , Matsukura Shigeru , Kuma Kanji , Imura Hiroo
Published: December 2008

In order to estimate thyroid stimulating immunoglobulins (TSI) in serum, a stable, reproducible and sensitive radioreceptor assay (RRA) capable of detecting 100 μU of thyroid stimulating hormone (TSH) has been developed using a proteolytic enzyme inhibitor (Trasylol), partially purified human TSH and particulate fractions of human thyroid homogenate. The binding of 125I-labelled TSH to the crude thyroid membranes was significantly increased from 2–3 % to 15–20 % in the presence of Trasylol (2000 KIU per tube). Further investigations suggested that Trasylol might inhibit the aggregation of 125I-labelled TSH during incubation with these membranes. With this assay system, the serum immunoglobulins from a great majority of untreated patients with Graves' disease were shown to inhibit the binding of 125I-labelled TSH to those membranes more markedly than those from control subjects. Therefore, this RRA for TSH was considered to provide a sensitive and stable method for detecting TSI.
RE-EXAMINATION OF HUMAN CALCITONIN RADIOIMMUNOASSAY
Authors: Argémi Bruno , Hours Marie Claude , Even Frédérique , Garguilo Gabrielle , Hollard Jean Marie
Published: December 2008

Evaluations of human immunoreactive calcitonin (IRCT) assay have been extensively reviewed. Labelled hormone was re-purified on carboxymethyl-cellulose in order to isolate a fraction containing mainly monoiodinated calcitonin, which was found to be very stable. Two antisera with different immunochemical characteristics were used for incubation studies, one of which was incubated with unextracted and extracted plasma samples. The sensitivity of the assays was 60 pg/ml plasma.

However, marked differences were observed in the results obtained by the three methods depending on the importance of the inhibitory effect of plasma on the binding of the tracer to antibodies. However, the absolute plasma IRCT level could not be related to the presence of calcitonin M, except in one case. Further studies are needed in order to ascertain the origin and the significance of the immunoreactive material which was detected in normal plasma by one antiserum.