bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF BROMOCRIPTINE (CB-154) ON OESTROGEN-INDUCED PROLACTIN RELEASE
Authors: D'Agata R. , Scapagnini U.
Published: December 2008

In order to study the interaction between oestrogens and bromocriptine on PRL release, we evaluated the ability of bromocriptine (CB-154) to counteract the oestrogen-induced PRL release in four hyperprolactinaemic amenorrhoeic women. Bromocriptine acutely administered induced a similar percentage of PRL decrease in the same patient before and after oestrogen administration. When bromocriptine was chronically administered, contemporary oestrogen injection did not affect PRL release. These results show that bromocriptine is able to block the release of PRL induced by oestrogens, suggesting an interaction between oestrogens and DA-mimetic compounds on PRL release.
HYPOPITUITARISM AND ARTIFICIAL VENTILATION
Authors: Barber S. G.
Published: December 2008

Anterior pituitary gland function was assessed in 50 patients maintained for more than 48 h on a mechanical ventilator. Partial hypopituitarism occurred in 7 patients which did not appear to affect survival and proved transient when subsequently re-assessed.

These results indicate that the pituitary infarcts previously reported in such patients are not clinically important.
PROLIFERATION OF PERIPHERAL LYMPHOID CELLS FROM EUTHYROID AND HYPERTHYROID INDIVIDUALS CULTURED WITH HUMAN THYROGLOBULIN
Authors: Blomgren Henric , Lundell Goran
Published: December 2008

Peripheral lymphoid cells from euthyroid and hyperthyroid subjects were tested for proliferative responses to human thyroglobulin in vitro using [3H] thymidine incorporation as assay. Non-fractionated lymphoid cells from both groups displayed weak stimulation. Using a rosette technique for separating sub-populations of lymphoid cells it was concluded that T-cells constituted the responding cells. The results indicate that both hyperthyroid and euthyroid subjects possess clones of T-cells which are reactive against human thyroglobulin.
EFFECTS OF ALPHA- AND BETA-ADRENERGIC BLOCKERS ON BINDING OF THYROTROPHIN TO FAT CELL MEMBRANE
Authors: Kishihara Michizo , Nakao Yoshinobu , Baba Yasuto , Ohgo Shozo , Matsukura Shigeru , Fujita Takuo , Kuma Kanji
Published: December 2008

Alpha- (phentolamine) and beta-adrenergic blocking agents (propranolol) and quinidine similarly enhance the specific binding of TSH to the guinea pig fat cell membranes over the concentration range of 2 × 10−4 to 4 × 10™3 m, increasing the binding affinity of TSH to the membranes. The percentage bound increased from 8 % in the absence of agents to 32 % (phentolamine), 29% (propranolol) and 24% (quinidine), respectively in the presence of these agents (1.5 × 10−3 m). Each minimal detectable quantity of TSH was approximately 10 μU per tube in the presence of these agents (10−3 m) as compared to 100 μU per tube in their absence. Both phentolamine and propranolol appeared to enhance the TSH binding to fat cell membranes through membrane-active, non-specific effects besides their alpha- and beta-adrenergic blocking activities.
POTENTIATION AND INHIBITION OF INSULIN RELEASE IN MAN FOLLOWING PRIMING WITH GLUCOSE AND WITH ARGININE – EFFECT OF SOMATOSTATIN
Authors: Efendić S. , Lins P. E. , Cerasi E.
Published: December 2008

The effect of priming normal subjects with glucose or with arginine on subsequent insulin and glucagon responses was investigated. A 60 min glucose infusion enhanced markedly the insulin response to a second glucose infusion, initiated 60 min after the end of the first one. When the insulin release caused by the first glucose infusion was blocked by somatostatin, enhancement of the response to the second infusion was still present. These results suggest that the action of glucose in inducing a time-dependent potentiation in the islet is not secondary to events associated with granular exocytosis.

Arginine, infused over 30 min, failed to enhance either the insulin or the glucagon response to a second arginine infusion given 60 or 90 min later.

When glucose was given as a rapid iv injection, it inhibited the insulin response to a second glucose load 30 min later. This effect of glucose was independent of its acute stimulation of insulin release: addition of somatostatin to the first glucose injection abolished the acute insulin response, but not the inhibition of the second response.

Priming with arginine, either given as an infusion or as a rapid iv injection, caused the inhibition of the subsequent insulin responses to arginine. In the case of priming with a 30-min arginine infusion, this inhibitory effect could be detected 60 and 90 min later. When priming was through rapid iv bolus, inhibition of the second insulin response appeared after 10 and 20 min, but faded out at 40–60 min. No such inhibition of the consecutive glucagon responses was observed. As for glucose, addition of somatostatin to the priming injection of arginine did not modify the subsequent inhibition of the insulin response.

The following is concluded: 1. Glucose-induced time-dependent inhibition and potentiation of subsequent insulin release is not generated by the insulin secretion process per se. 2. Arginine does not generate time-dependent potentiation of insulin or glucagon release. 3. Arginine generates time-dependent inhibition of subsequent insulin but not of glucagon release. In analogy to glucose this effect is not mediated by the insulin release per se. 4. The mechanisms of acute initiation of insulin release, of time-dependent potentiation and of time-dependent inhibition are different; somatostatin acts exclusively on the acute initiation.
STUDY OF GLUCOSE TOLERANCE AND THE DYNAMIC PROPERTY OF INSULIN SECRETION. ANALYSIS OF INTRAVENOUS GLUCOSE TOLERANCE TEST WITH THE AID OF A CONTROL THEORY
Authors: Kawamori Ryuzo , Shichiri Motoaki , Murata Teishi , Nomura Makoto , Shigeta Yukio , Abe Hiroshi
Published: December 2008

The dynamic property of insulin secretion in relation to glucose tolerance was investigated quantitatively during iv glucose tolerance tests in 237 cases. The following results were obtained; 1) Glucose clearance constant (k-value) was not constant but variable with time and should be expressed as a function of time, K(t). In normal glucose tolerance, K(t) became greater with time. 2) Glucose-induced insulin secretion was expressed as the function of a proportional plus derivative response to glucose concentration. A weighting function of derivative response, reflecting the insulin secretion per unit of rate of change in blood glucose concentration, was calculated from blood glucose concentration (input) and insulin concentration (output) by the deconvolution method. It was clearly shown that the gain in weighting function was small and the response was slow even in the individual whose glucose tolerance was slightly impaired. 3) The greater the weighting function, the larger the change in K(t).
ENHANCED TESTOSTERONE IN FEMALE PATIENTS WITH ANOREXIA NERVOSA: ITS NORMALIZATION AFTER WEIGHT GAIN
Authors: Baranowska B. , Zgliczyński S.
Published: December 2008

In order to elucidate the mechanism of disturbances of gonadal hormones secretion in anorexia nervosa 14 female patients were investigated. A control group also consisted of 14 women of the same age. The serum LH, progesterone, oestrogens: oestrone + oestradiol (Oe1 + Oe2), oestriol (Oe3) and testosterone were determined by radioimmunological methods. In patients with anorexia nervosa the serum testosterone and Oe3 concentrations were dramatically elevated, whereas LH, progesterone and Oe1 + Oe2 were decreased as compared with the control group. Considerable weight gain induced by cyproheptadine treatment caused a normalization of the serum testosterone and Oe3 concentrations in all the patients. A negative correlation between the testosterone level and the deficit in body weight was observed. The mechanism causing the dramatically high serum testosterone concentration in the female patients with anorexia nervosa is discussed.
INTRA-AMNIOTIC THYROXINE (T4) ABSORPTION BY THE PREMATURE HUMAN FOETUS
Authors: Sack Joseph , Mashiach Shlomo , Barkai Gad , Lunenfeld Bruno , Brish Michael , Goldman Boleslav , Serr David M.
Published: December 2008

We reported previously on the beneficial influence of intra-amniotic T4 injection in accelerating human foetal lung maturity. Twenty-four h after T4 (250 μg) intra-amniotic injection, the mean cord serum T4 concentration in 13 premature newborns was 17 ± 2.1 μg/100 ml, while the T4 concentration in a matched group was only 11.6 ± 0.9 μg/100 ml: in 5 of the infants who received intra-amniotic thyroxine T4 was measured 12 h post-partum and rose from 16.1 ± 1.8 to 24.3 ± 2.6 μg/100 ml. No change in maternal T4 concentration was observed. The mean cord serum T4 concentration in premature newborns delivered more than 3 days following T4 intra-amniotic injection, however, was not significantly different from that of the controls. These data suggest that T4 (250 μg) injected intraamniotically is absorbed by the premature human foetus. Furthermore, the hyperthyroxinaemia is only transient, and does not prevent the post-natal T4 surge.
PLASMA TESTOSTERONE IN MALE PUBERTY
Authors: Knorr D. , Beckmann D. , Bidlingmaier F. , Helmig F.-J. , Sip pell W. G.
Published: December 2008

Plasma testosterone was determined by radioimmunoassay in 36 prepubertal boys with hypospadia prior to and 3 days after stimulation with 5000 IU of human chorionic gonadotrophin (hCG). As a control group, 30 boys of comparable age, predominantly with unilateral cryptorchidism, were studied. The increase in plasma testosterone levels after hCG was (median and range) 204 (83–393) ng/100 ml in the control group, whereas in the hypospadiac group a median increase of only 90 (33–272) ng/100 ml was found. The difference between the median testosterone levels after hCG stimulation in the two groups investigated is statistically highly significant (P < 0.0001). After hCG stimulation, 13 out of the 36 boys with hypospadia did not reach the lowest stimulated testosterone level (87 ng/100 ml) found in the control group. It is concluded that a substantial portion of the aetiologically obscure cases of hypospadia are caused by an endocrine testicular insufficiency.
ADRENERGIC INPUTS TO THE AMYGDALA AND THE CONTROL OF GONADOTROPHIN RELEASE
Authors: Borrell José , Piva Flavio , Martini Luciano
Published: December 2008

Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects.

From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.
EFFECT OF ANDROGENS ON PROLACTIN (PRL) RELEASE IN HUMANS
Authors: D'Agata R. , Gulizia S. , Vicari E. , Aliffi A. , Polosa P.
Published: December 2008

In order to evaluate whether androgens were able to affect PRL release, testosterone and dihydrotestosterone were injected intramuscularly in male and female subjects. PRL blood levels were not modified by testosterone either in healthy males or in amenorrhoeic women, and PRL release in males proved unaffected by dihydrotestosterone at the dose used.
DIURNAL VARIATIONS OF PROLACTIN IN THE PLASMA OF MATURING FEMALE RATS BEARING HYPOTHALAMIC LESIONS
Authors: Alvarez Edgardo O.
Published: December 2008

Previous evidence from our laboratory suggested a possible involvement of prolactin (PRL) in the induction of precocious puberty due to hypothalamic lesions in maturing female rats. In the present report the concentrations of PRL in plasma of lesioned and control rats were determined three times a day at three different periods of puberty. Lesions were produced in 20 day-old rats by a radiofrequency current in the anterior hypothalamic area (AHA). Intact littermates were used as control. Respectively 23, 25 and 28 day-old lesioned and control rats were bled at 08.00, 12.00 or 16.00 h. PRL levels, measured by RIA were determined from plasma aliquots. In control rats, elevated plasma PRL levels were found in the afternoon. Hypothalamic lesion induced a tendency to elevate tonically the PRL plasma concentrations which was evident at 16.00 h in 23 and 25 day-old rats and at 08.00 and 12.00 h in 28 day-old rats. The present results give additional support to our previous suggestion that PRL secretion is modified by the effect of lesions in the AHA.
INCREASED INSULIN SENSITIVITY AND CELLULAR INSULIN BINDING IN OBESE DIABETICS FOLLOWING TREATMENT WITH GLIBENCLAMIDE
Authors: Beck-Nielsen Henning , Pedersen Oluf , Lindskov Hans Otto
Published: December 2008

The aim of the present study was to examine the effect of glibenclamide on the insulin receptors, the insulin sensitivity and the insulin secretion in obese non-ketotic diabetics.

Two groups of 9 obese diabetics were studied before and after 10 days' treatment with a 1200 Kcal's diet and a 1200 kcal's diet + 10 mg/day of glibenclamide, respectively. In the group treated with diet alone we found no significant alteration of the insulin secretion pattern (P > 0.1). However, the insulin sensitivity increased 37 % (P < 0.01). Furthermore, the insulin binding to monocytes increased (P < 0.01) due to a 36% rise of the binding affinity. In the group treated with glibenclamide and diet the insulin secretory pattern was unchanged, too (P > 0.1). The insulin sensitivity, however, increased 83% (P < 0.01). Moreover, the insulin binding was raised (P < 0.01) as a result of a 80 % rise of the number of insulin receptors.

In 4 patients who were treated with diet (1200 kcal/day) plus glibenclamide and in 5 patients who were treated with diet alone (1200 kcal/day) the insulin binding to monocytes was studied during treatment for 1 year. After 1 year we found a significantly (P < 0.05) higher cellular insulin binding in the glibenclamide treated patients compared to the patients who got diet alone.

We conclude that 1) the augmentation of the insulin sensitivity is of great importance for the normalization of the diabetic state in obese, 2) the increase in insulin binding may be of importance for the increase in insulin sensitivity, 3) glibenclamide appears to enhance the insulin sensitivity through an increase in the number of insulin receptors.
17-HYDROXYPROGESTERONE IN THE COSYNTROPIN TEST: RESULTS IN NORMAL AND HIRSUTE WOMEN AND IN MILD CONGENITAL ADRENAL HYPERPLASIA
Authors: Gourmelen M. , Pham-Huu-Trung M. T. , Bredon M. G. , Girard F.
Published: December 2008

The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH).

The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle.

One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.
INCIDENCE OF IMMUNE COMPLEX NEPHRITIS FOLLOWING ACTIVE IMMUNISATION WITH A TESTOSTERONE-3-BSA CONJUGATE OR BSA ALONE
Authors: Witting Ch. , Wickings E. J. , Nieschlag E.
Published: December 2008

Before immunisation with hormones can be applied in therapeutic medicine, the possible immunological side effects should be investigated. Therefore the kidneys of 20 rabbits immunised with testosterone-BSA conjugates were examined 4 to 30 weeks after immunisation for the presence of immune complex precipitation and glomerulonephritis. Eighty-five per cent showed differing degrees of precipitation and 50 % had an exudative glomerulonephritis. None of the kidneys from normal control rabbits or those immunised with complete Freund's adjuvant or BSA showed any signs of immune complex precipitation, although high anti-BSA titres were present in the BSA-immunised animals (1/3000 – 1/25 000). BSA antibodies could not be detected in the rabbits immunised with testosterone-3-BSA. In the light of these findings active immunisation with steroid-BSA conjugates would not be advisable as a means of therapy.
PITUITARY-THYROID FUNCTION IN SPIRONOLACTONE TREATED HYPERTENSIVE WOMEN
Authors: Smals A. G. H. , Kloppenborg P. W. C. , Hoefnagels W. H. L. , Drayer J. I. M.
Published: December 2008

Four weeks high dose spironolactone treatment (Aldactone® Searle, 100 mg q. i. d.) significantly enhanced the TSH (Δ max. 8.5 ± 4.1 vs. 4.6 ± 3.1 μU/ml, P < 0.05) and T3 (Δ max. 32±27 vs. 11 ± 16 ng/100 ml, P < 0.05) responses to an intravenous TRH/LH-RH bolus injection in 6 eumenorrhoeic euthyroid hypertensive women, without affecting basal serum TSH, T3 or T4 levels or the basal and stimulated LH, FSH and prolactin values (P > 0.10). The mean serum testosterone, 17-hydroxyprogesterone and oestradiol levels were also similar before and during therapy. Spironolactone, possibly by virtue of its antiandrogenic action, may exert its enhancing effect on pituitary-thyroid function by modulating the levels of receptors for TRH in the thyrotrophs or by altering the T3 receptor in the pituitary permitting a greater response to TRH.
LIVER CIRRHOSIS AND OESTROGEN METABOLISM – PERFUSION STUDIES WITH CIRRHOTIC RAT LIVERS
Authors: Höller Michael , Dengler Karin , Fabricius Renate , Breuer Heinz
Published: December 2008

Radioactive oestrone and oestradiol-17β were perfused through normal and cirrhotic livers of rats. Liver cirrhosis had been induced by a combined application of carbon tetrachloride and azathioprine.

The hepatic uptake of both oestrogens by cirrhotic livers was reduced; the uptake of oestrone was more affected than that of oestradiol-17β,

The pattern of oestrogen metabolites indicated a reduction of the sulphotransferase activity in cirrhotic livers. The activity of other enzymes of oestrogen metabolism were similar in normal and cirrhotic livers.

The amount of oestrogen glucuronides excreted into the bile was significantly less in cirrhotic livers although the bile volume was larger in cirrhotic than in normal livers.

The release of oestrogen metabolites into the circulating medium was considerably higher during perfusion of cirrhotic livers.

From the findings presented here it is concluded that the turnover of oestrogens is slower in cirrhotic than in normal livers. Moreover, it may be speculated that the distribution volume of the oestrogen metabolites is smaller in rats with liver cirrhosis, due to a disturbed enterohepatic circulation. This results in higher oestrogen concentrations in extracellular fluids, thus supporting the concept of hyper-oestrogenism in liver cirrhosis.
HEPATIC UPTAKE OF DESIALYLATED TESTOSTERONE-OESTRADIOL-BINDING GLOBULIN IN THE RAT
Authors: Suzuki Yasuyuki , Sinohara Hyogo
Published: December 2008

Testosterone-oestradiol-binding globulin (TeBG) isolated from bovine serum was desialylated by treatment with neuraminidase and its properties were compared with intact TeBG. No significant differences were observed in the testosterone-binding capacity or antigenic determinant, but electrophoretic mobility of asialo-TeBG decreased slightly. When injected into rat vein, 125I-labelled asialo-TeBG was rapidly taken up by the liver, whereas 125I-labelled intact TeBG remained in the circulation for a much longer period. Galactose oxidase treatment of asialo-TeBG, which presumably oxidized the primary alcohol of galactose at C-6 to an aldehyde, caused a reversion of its survival time in the blood to that of intact TeBG. When incubated with isolated rat liver cells at 20°C, the desialylated, but not intact, TeBG was rapidly taken up, and its uptake was inhibited by excess amount of asialo-orosomucoid. Under these conditions in vitro, [3H] testosterone bound to asialo-TeBG was taken up by the liver cells together with the asialo-TeBG.
OVULATION BLOCKADE AND RECEPTIVITY IN THE CYCLIC RAT
Authors: van Riemsdijk Alice , Zeilmaker G. H.
Published: December 2008

The onset and decline of sexual receptivity was determined around oestrus in intact 5-day cyclic rats and in animals in which spontaneous ovulation was inhibited with nembutal.

It was observed that early receptivity (before the critical hours at 14–16 h) could be induced by prior exposure of pro-oestrous females to male rats during the morning at pro-oestrus. In most cases early receptivity was associated with a failure to block ovulation with nembutal administered at 14 h.

In cyclic rats receptivity disappeared on the day of oestrus between 8 and 10 a. m. By contrast the period of receptivity was prolonged for 24 h in animals in which ovulation was inhibited by nembutal. Reflex ovulation could be induced by exposure of nembutal-blocked rats to intact as well as to pudendectomized male rats, which latter cannot achieve intromissions. This illustrates the limited role of female genital stimuli in the induction of reflex ovulation.

Progesterone (1.25 or 5 mg) injected at pro-oestrus during nembutal sedation did not have an attenuating effect on receptivity 24 h later. It is concluded that LH-surge dependent progesterone secretion at pro-oestrus is not essential for the induction and termination of receptivity around oestrus and that hormones, presumably oestrogens, secreted by the persistent pre-ovulatory follicles, are responsible for the prolonged period of receptivity following nembutal blockade of ovulation.
ISOLATION OF HIGHLY PURIFIED SEX HORMONE BINDING GLOBULIN (SHBG): EVIDENCE FOR MICROHETEROGENEITY
Authors: Mischke W. , Weise H. C. , Graesslin D. , Rusch R. , Tamm J.
Published: December 2008

Highly purified sex hormone binding globulin (SHBG) was isolated in milligram amounts from a human serum fraction (Cohn IV-4). The final preparation was homogeneous by the criteria of polyacrylamide-gel electrophoresis. Immunological evidence for purity could be given by double diffusion according to Ouchterlony. However, following gel isoelectric focusing highly purified SHBG displayed four different bands, as could be demonstrated by staining as well as by a photoscan of the [3H]5α-dihydrotestosterone-SHBG complex. After incubation with neuraminidase the microheterogeneity of SHBG disappeared and the asialo-SHBG showed only one band.
FAMILIAL THYROXINE-BINDING GLOBULIN DEFICIENCY IN ASSOCIATION WITH NON-TOXIC GOITRE
Authors: Bratusch-Marrain Paul , Haydl Hannes , Waldhäusl Werner , Dudczak Robert , Graninger Wolfgang
Published: December 2008

A kindred is presented in which 4 members in 3 generations showed absent or reduced serum concentrations of thyroxine-binding globulin (TBG). TBG was undetectable by radioimmunoassay in one male and decreased to varying extent in 3 female patients (4.0, 4.2 and 8.6 μg/ml; normal range 12.5–26.0 μg/ml). Total thyroxine serum concentrations in the affected subjects were well in the hypothyroid range without clinical evidence of hypothyroidism. The mode of transmission of the trait was consistent with X-chromosome linkage. A high incidence of non-toxic goitre was also present in most of the family members examined irrespective of TBG levels. The transmission of the goitre trait was compatible with autosomal dominant inheritance. Thus its association with transmission of TBG deficiency was interpreted as not causal but coincidental.
STUDIES ON A RECEPTOR ASSAY FOR AN ANTIBODY TO HUMAN THYROID PLASMA MEMBRANE
Authors: Ochi Yukio , Hosoda Shiro , Hachiya Takashi , Yoshimura Manabu , Miyazaki Tadayoshi , Kajita Yoshihiro
Published: December 2008

A receptor assay was examined for the thyroid stimulating immunoglobulin using [125I]LATS. The principle of this method is the determination of displaced [125I]LATS from thyroidal plasma membrane (PM) by test serum. LATS-IgG without thyroidal antibodies was labelled with 125I, and radioactivity (RA) bound to purified PM from human thyroid was used as [125I] LATS. In the routine receptor assay, human thyroidal PM fraction, 0.1 ml of test serum, and [125I]LATS were incubated. Then [125I]LATS bound with the PM was determined after centrifugation. LATS positive serum showed a significant displacement. However, TSH (human and bovine), hCG and cholera toxin did not displace [125I]LATS from the plasma membrane.

The bound per cent in euthyroid subjects was about 29 ± 3 % (mean ± sd). The displacing activity was positive in both hyperthyroid patients and in Hashimoto's thyroiditis, while in simple goitre and in hypothyroid patients with increased serum TSH it was always negative. LATS positive sera showed strong displacing activity in 16 of 17 cases, but LATS negative sera in hyperthyroid patients were positive in only 70 %. The displacing activity was also positive in all sera with positive precipitating antibody for thyroglobulin (TG), while patients with the positive haemagglutination antibody for TG (TRC: ≦ 107)in Hashimoto's disease were positive in about 50 % of cases. The displacing activity was not affected by absorption of TG antibody. Microsomal antibody in Hashimoto's disease was suggested to have an effect on the displacing activity. Although this method is not specific for determining LATS, this assay may be useful for examining thyroid plasma membrane binding immunoglobulin.
PLASMA CLEARANCE OF CORTISOL AS A FUNCTION OF PLASMA CORTISOL LEVELS IN NORMAL AND OBESE PERSONS AND IN PATIENTS WITH URAEMIA OR CIRRHOSIS OF THE LIVER
Authors: Deck K. A. , Baur P. , Hillen H.
Published: December 2008

Plasma cortisol levels in 2 normal persons, 2 obese persons, 2 uraemic patients, and 2 patients with cirrhosis of the liver were raised in 4 steps by a combination of iv priming doses and continuous infusions of cortisol. Plasma cortisol levels and transcortin binding were measured as well as plasma clearance rates of labelled and unlabelled cortisol during each of the 5 experimental periods. Plasma cortisol levels increased less and plasma clearance rates of labelled and unlabelled cortisol increased more in obese persons than in normal persons; in patients with disturbed metabolism of cortisol (uraemia, cirrhosis of the liver) the reverse is true. Plasma clearance rates of free cortisol were calculated and differed from an estimated hepatic plasma flow of 0.7 1/min under certain conditions. Since free cortisol is metabolized faster than transcortin-bound cortisol, increasing plasma clearance rates of cortisol are probably due to increasing ratios free/bound cortisol when total plasma cortisol levels are raised. Low plasma clearance rates of cortisol in uraemia and cirrhosis of the liver are thought to be due to endproduct inhibition, respectively reduced liver cell mass.
RADIOIMMUNOASSAY FOR 2-METHOXYOESTRONE IN HUMAN PLASMA
Authors: Emons Günter , Ball Peter , Postel Gertrud v. , Knuppen Rudolf
Published: December 2008

A bovine serum albumin conjugate of 2-methoxyoestrone was used for the preparation of highly specific antibodies in rabbits. Cross-reactivity for catecholoestrogens and monophenolic steroids was below 0.3 %. Only 2-methoxyoestradiol cross-reacted with 44 %. An assay procedure for the determination of unconjugated and conjugated 2-methoxyoestrone in human plasma is described. The following mean plasma concentrations (pg/ml) were found (unconjugated/conjugated): children 61/1130, young men 74/1320, elderly men 109/1260, cycling women 131/1040, post-menopausal women 102/1420, and pregnant women 3980/5850.
SERUM THYROGLOBULIN IN PATIENTS WITH TOXIC AND NON-TOXIC GOITRES COMPARED TO SEX- AND AGE-MATCHED CONTROL SUBJECTS
Authors: Feldt-Rasmussen Ulla , Bech Karine , Date John
Published: December 2008

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started.

Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively.

It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.
BROMOCRIPTINE-INDUCED MODULATION OF PLASMA ALDOSTERONE RESPONSE TO ACUTE STIMULATIONS
Authors: Birkhäuser M. , Riondel A. , Vallotton M. B.
Published: December 2008

The influence of the dopaminergic agent 2-bromoergocryptine on plasma aldosterone response to acute stimulations was assessed in 14 normal male volunteers. Without modifying basal plasma aldosterone levels or urinary aldosterone excretion, bromocriptine retarded and diminished significantly the plasma aldosterone response to angiotensin II or ACTH, but did not alter the response to upright posture. These results point to a bromocriptineinduced modulation of the plasma aldosterone response to direct stimulations at the adrenal level. The present work brings further evidence for an effect of the dopaminergic system on the physiological control of aldosterone.
CUSHING'S SYNDROME DUE TO ADRENOCORTICAL CARCINOMA A COMPHRENSIVE CLINICAL AND BIOCHEMICAL STUDY OF PATIENTS TREATED BY SURGERY AND CHEMOTHERAPY
Authors: Kelly W. F. , Barnes A. J. , Cassar J. , White M. , Mashiter K. , Loizou S. , Welbourn R. B. , Joplin G. F.
Published: December 2008

Four post-mencpausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission.
DIFFERENT BIOLOGICAL ACTION OF CORTICOSTEROIDS, CORTICOSTERONE AND CORTISOL, AS A BASE OF ZONAL FUNCTION OF ADRENAL CORTEX
Authors: Kahri A. I. , Voutilainen R. , Salmenperä M.
Published: December 2008

The effects of corticosterone and cortisol in concentrations attainable in the adrenal gland were studied on ACTH-induced steroidogenesis in cultured cortical cells of foetal human and rat adrenals. Corticosterone at a concentration of 5.8 × 10−5 mol/l clearly inhibited cortisol production (65.5%; P < 0.005) and simultaneously increased androgen production in tissue culture of foetal human adrenals. Cortisol at a concentration of 2.8 × 10−4 mol/l clearly inhibited 18-OH-DOC (74.0 %, P < 0.001) and aldosterone (83.7 % P < 0.005) production in tissue culture of foetal rat adrenals. In primary culture of foetal human adrenals cortisol did not decrease aldosterone production absolutely, but it significantly decreased the relative amount of aldosterone with respect to corticosterone. Cortisol did not inhibit corticosterone production in either culture.

The results demonstrate that cortisol and corticosterone have qualitatively different effects on adrenal steroidogenesis and that these steroids may play a basic role in the functional zonation of the adrenal gland.
PROLACTIN-SECRETING PITUITARY ADENOMAS: PROLACTIN DYNAMICS BEFORE AND AFTER TRANSSPHENOIDAL SURGERY
Authors: Barbarino Antonino , de Marinis Laura , Menini Edoardo , Anile Carmelo , Maira Giulio
Published: December 2008

Twenty women with hyperprolactinaemia secondary to a pituitary adenoma were studied before and after selective transsphenoidal removal of the tumour.

Pre-operatively, thyrotrophin-releasing hormone (TRH) (200 μg iv) and metoclopramide (MCP) (10 mg po) did not produce a positive PRL response in the tumour patients. By contrast, 14 post-partum lactating women, who were used as controls, exhibited a positive response to MCP administration. Methergoline (4 mg po) was shown to decrease serum PRL levels in 8 normal subjects, in 6 puerperal women, and 9 of 10 tumour patients. Bromoergocriptine (CB-154, 2.5 mg po) decreased serum PRL levels in 10 tumour patients.

Following transsphenoidal removal of the adenoma serum PRL levels were reduced in all patients, and returned to normal in 14 patients. Prognostics for completely normalizing PRL secretion after transsphenoidal surgery is better when initial serum PRL levels are below 200 ng/ml.

After surgery all hyperprolactinaemic patients failed to show a positive PRL response to TRH and MCP. Nine normoprolactinaemic patients had a positive response to both stimuli while 3 patients failed to show a positive response immediately following surgery.

Long-term studies, however, showed that a positive PRL response was obtained in all patients tested 8–14 months after treatment.

A positive PRL response to methergoline and bromocriptine was observed post-operatively in the patients tested regardless of their basal PRL level. Data from this study indicate that surgically proven PRL-secreting adenomas are invariably associated with negative PRL responses to TRH and MCP.

The normalization of the prolactin regulation after surgery points toward the intrapituitary localization of the lesion associated with PRL-secreting adenomas.
STUDY ON THE REPRODUCIBILITY OF HUMAN PROLACTIN RESPONSE TO SULPIRIDE, BENSERAZIDE, INSULIN HYPOGLYCAEMIA AND ARGININE INFUSION
Authors: Pontiroli Antonio E. , Gala Richard R. , Pellicciotta Gabriele , De Pasqua Anna , Girardi Anna M. , Pozza Guido
Published: December 2008

In order to evaluate the spontaneous variability of prolactin (PRL) release in response to various stimuli applied repeatedly on different occasions, groups of 5 to 12 subjects each underwent consecutive identical tests with one of the following stimuli applied at 3–6 days' intervals: sulpiride (100 mg im), benserazide (50 mg po), insulin hypoglycaemia (0.1 U/kg b. w. iv) and arginine infusion (25 g iv in 30 min). When repeated in the same subjects, arginine and benserazide yielded superimposable results. In contrast to this, insulin hypoglycaemia yielded significantly lower PRL release, while the PRL response to the second sulpiride test was significantly higher than to the first one. When an interval of 10 days was left between two consecutive sulpiride tests, an identical PRL release was observed. These results indicate that arginine and benserazide are reproducible tests for PRL secretion and it is possible that the decreasing effect of insulin hypoglycaemia on PRL release is due to the stressful effect of the stimulus. Finally, sulpiride probably enhances both PRL release and synthesis thus making greater amounts of PRL available to a subsequent stimulus. Since some of the above stimuli are usual tools for the study of the neuroendocrine control of PRL secretion, our findings suggest that caution appears necessary in attributing to any (neuroactive) drug an effect which might be merely due to a lack of reproducibility of the stimulus employed.
OSTEOPOROSIS IN HYPERTHYROIDISM ESTIMATED BY PHOTON ABSORPTIOMETRY
Authors: Linde J. , Friis Th.
Published: December 2008

The degree of osteoporosis in hyperthyroidism before and during treatment with carbimazole was studied by photon absorption technique of the right forearm and calcaneus.

In addition serum total calcium, serum ionized calcium, serum phosphorus and serum alkaline phosphatase were determined.

A group of 96 patients suffering from untreated hyperthyroidism (85 women and 11 men) was studied (79 of these patients were also followed during treatment) and compared to a control group of 157 persons (107 women and 50 men).

The women were divided into two groups: ≤ 45 years old and more than 45 years old.

In all groups untreated hyperthyroid patients showed lower bone densities compared to the control group, but this was only significant in women. During treatment all groups showed a significant increase in density. After 3–6 months of treatment bone density in the calcaneus increased 12 % and in the forearm 1.5 %; after 6 months – 3 years 33 % and 31 %, respectively. At that time bone density was normalized.

There was no correlation between bone density in hyperthyroid patients and duration and severity of the disease.

The biochemical changes were characterised by increases in serum alkaline phosphatase (26 %), serum total calcium (16 %) and serum ionized calcium concentration (17 %) in cases of untreated hyperthyroidism. Serum phosphorus concentration did not change. A correlation was found between elevation of the alkaline phosphatase and decreased bone density.
TESTICULAR ACTIVITY IN CUSHING'S DISEASE
Authors: McKenna Terence J. , Lorber Daniel , Lacroix Andre , Rabin David
Published: December 2008

Plasma testosterone levels were suppressed in 6 of 8 mature male patients with Cushing's disease, all of whom complained of loss of libido and decreased sexual potency. Gonadotrophin levels, both under basal conditions and in response to LH-RH, were generally normal. The testicular response to stimulation with hCG was brisk in the 2 patients examined. Oestradiol levels were slightly elevated in 2 patients and prolactin levels were normal in all patients. Thus, male patients with Cushing's disease demonstrated normal gonadotrophin levels in the presence of suppressed testosterone, or, viewed from a slightly different prospect, low testosterone levels despite normal gonadotrophins. Neither oestradiol nor prolactin excess appeared to account for the observations. Possible explanations for these findings include (a) a combination of impaired hypothalamic and testicular function, and (b) a resetting downwards of the level of testosterone that is seen as appropriate by the disordered hypothalamic-pituitary unit. Following correction of cortisol excess in Cushing's disease, testosterone levels rose into the normal range.
INHIBITORY EFFECTS ON GONADOTROPHIN SECRETION AND GONADAL FUNCTION IN MEN DURING CHRONIC TREATMENT WITH A POTENT STIMULATORY LUTEINIZING HORMONE-RELEASING HORMONE ANALOGUE
Authors: Bergquist Christer , Nillius Sven Johan , Bergh Torbjörn , Skarin Göran , Wide Leif
Published: December 2008

Long-term treatment with the potent and long-acting stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was given to 4 healthy men to study its effects on pituitary gonadotrophin secretion and gonadal function. Five μg of the LRH agonist was self-administered sc once daily over 17 weeks. Weekly basal blood samples were obtained for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone. The gonadotrophin responses to the LRH analogue were also determined during the treatment period. LRH tests were performed after treatment. Seminal fluid specimens were collected during and after treatment.

A reduction of the basal serum gonadotrophin and testosterone levels were observed during the treatment period. The FSH and LH responses to the analogue were also diminished. After discontinuation of treatment the gonadotrophin and testosterone concentrations returned to pre-treatment levels within a week. The PRL levels and the seminal fluid specimens did not show any significant changes during the study period. The results suggest that chronic treatment with D-Ser(TBU)6-EA10-LRH has an inhibitory effect on the pituitary gonadotrophin secretion in healthy men. It seems likely that the reduced testosterone level is secondary to the diminished gonadotrophin secretion.
DEPLETION OF COLLOID 27S AND LARGER THYROID IODOPROTEINS FOLLOWING TREATMENT WITH PROPYLTHIOURACIL
Authors: Smeds S. , Anderberg B.
Published: December 2008

By means of a micropuncture technique and microgel electrophoresis the luminal content of single rat thyroid follicles were analysed during PTU treatment for 4 weeks. The relative amount of aggregates of thyroglobulin (i. e. the 27S iodoprotein and larger complex) was reduced from 15 per cent to approximately 3 per cent after 48 h. The aggregates were practically absent after 2 weeks. The thyroglobulin fraction was the predominant colloid constituent. The protein concentration of the colloid was not changed at the end of the period of PTU treatment (8.9 g/100 ml). It is concluded that PTU inhibits the aggregation of thyroglobulin to a larger complex. The results further indicate that the aggregates of thyroglobulin are preferentially localized to the periphery of the lumen in the larger follicles.
CORTICOSTERONE SECRETING ADRENAL CARCINOMA AND EMPTY SELLA TURCICA: A CASE REPORT
Authors: Krølner Bjørn , Larsen Steen , Nielsen Meta Damkjær
Published: December 2008

Pituitary adenoma was suspected in a woman of 74 with hypercorticism, hypokalaemic alkalosis and radiographically enlarged sella turcica. However, non-suppressibility of steroid excretion by high-dose dexamethasone and low plasma concentration of ACTH suggested adrenal tumour. Detailed analysis of urinary steroid excretions demonstrated unusually large amounts of corticosterone metabolites, 14.6 mg/24 h compared to a mean normal value of 0.5 mg. The basal levels of the remaining pituitary hormones were unremarkable.

The patient died incidentally before a planned adrenalectomy. The autopsy disclosed an adrenal carcinoma and an empty sella turcica. The enlarged pituitary fossa was lined by a narrow rim of histological normal pituitary tissue.
EFFECT OF TWO PROSTAGLANDIN SYNTHESIS INHIBITORS, INDOMETHACIN AND ACETYLSALICYLIC ACID, ON PLASMA ACTH AND CORTISOL LEVELS IN MAN
Authors: Cavagnini F. , Di Landro A. , Maraschini C. , Invitti C. , Pinto M. L.
Published: December 2008

The aim of this study was to investigate the possible role of prostaglandins (PG) in the control of the hypothalamic-pituitary-adrenocortical axis in normal volunteers. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycaemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycaemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical cortisol production. Our findings support the concept, based on animal studies, that PG enhance hypothalamic CRF release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary.
DYNAMIC CHANGES IN HYPOTHALAMIC LH-RH LEVELS ASSOCIATED WITH THE OVARIAN STEROID-INDUCED GONADOTROPHIN SURGE
Authors: Kalra Satya P. , Kalra Pushpa S.
Published: December 2008

Pro-oestrous-type LH surges were induced by treating ovariectomized rats (day 0) with either oestradiol benzoate (OeB, 40 μg/rat) or oestrogen (10 μg/rat followed by progesterone (4 mg/rat, day 2, OeBP). To characterize the temporal changes associated with the LH surge on day 2, LH-RH levels in the medial basal hypothalamus (MBH) and the pre-optic area (POA) were analyzed by RIA in rats sacrified at hourly intervals between 10.00–19.00 h. Following these treatments the LH-RH content of POA fluctuated somewhat but no definite pattern was observed. In OeB rats, the MBH LH-RH levels were unchanged through the initial LH surge period (13.00–15.00 h) declining significantly, as in the OeBP group, near the end of the surge period (19.00 h). However, in OeBP rats, the MBH LH-RH contents decreased at 14.00 h and these were followed by markedly elevated levels between 15.00–17.00 h coincident with maximal increments in serum LH. The OeBP group alone showed a surge of serum FSH.
SUPPRESSION OF PROLACTIN SECRETION BY LISURIDE THROUGHOUT THE MENSTRUAL CYCLE AND IN HYPERPROLACTINAEMIC MENSTRUAL DISORDERS
Authors: Bohnet H. G. , Hanker J. P. , Horowski R. , Wickings E. J. , Schneider H. P. G.
Published: December 2008

Normally menstruating volunteers as well as patients with hyperprolactinaemic menstrual disorders were treated with lisuride hydrogen maleate (200 μg b.i.d.), an ergoline derivative with dopaminergic properties. Within 3 h after an oral dose of 200 μg lisuride, PRL levels decreased significantly in all subjects to a plateau which lasted up to 3 h. Thereafter a gradual increase of serum PRL was noted.

In the normally menstruating volunteers lisuride treatment did not result in any significant change of gonadotrophin or of sex steroid secretion, while both, basal as well as metoclopramide (MTCL) stimulated PRL release were significantly diminished. The inhibition of PRL secretion in patients with short luteal phases resulted in an increase of luteal progesterone output. In both treated groups ovulation occurred 1 to 5 days earlier in cycles on lisuride than in control cycles. LH-RH/MTCL tests performed in the patient bearing a pituitary prolactinoma before and after lisuride treatment revealed a continuous increase of pituitary LH pools, while PRL secretion decreased under lisuride therapy. Subsequently ovulation and menstruation occurred.

The data presented demonstrate that lisuride is a potent inhibitor of PRL secretion and has proven its clinical usefulness for treatment of hyperprolactinaemic menstrual disorders. Application of lisuride resulted in an increase of luteal progesterone secretion in previously demonstrated corpus luteum insufficiency as well as in restoration of normal cyclical feedback mechanisms in tumorous hyperprolactinaemic anovulation. The MTCL-PRL stimulation test is suitable to monitor PRL suppression during lisuride treatment, while LH-RH testing reveals the effectiveness of lisuride by demonstrating an increase of pituitary gonadotrophin pools.