bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF THYROTROPHIN RELEASING HORMONE ON PITUITARY AND THYROID FUNCTION IN PRE- AND POST-NATAL LAMBS
Authors: Wallace A. L. C. , Nancarrow C. D. , Evison B. M. , Radford H. M.
Published: December 2008

Thyrotrophin releasing hormone (TRH, 50 μg) was injected into chronically catheterized foetuses at various ages from 107 days gestation and into lambs up to 13 days post-partum. Changes in the concentrations of TSH, prolactin, T3 and T4 in plasma were measured by radioimmunoassay.

The initial concentration of TSH (1.2 ± 0.2, sem, ng/ml) and its increase in response to TRH was similar at all foetal ages tested. However, both pre-injection concentrations of prolactin in plasma and the magnitude of the response to TRH increased with foetal age. The responses in lambs up to 13 days old were greater than those in the foetuses.

The concentration of T4 was 6.3 μg/100 ml plasma in a 107 day-old foetus This had doubled by 128 days but declined again towards parturition. After TRH injection plasma T4 concentration increased in lambs, but showed little or no change in 113 and 137 day-old foetuses.

The concentration of T3 increased from 4–5 ng/100 ml plasma in 110–116 day-old foetuses to 40 ng/100 ml just prior to parturition. Values were high in the young lambs (362 ± 79 ng/ml) but declined with increasing age. There was no response to TRH up to 130 days gestation. A small response was obtained in a 137 day-old foetus while the concentration of T3 rose from 37 to 90 ng/100 ml in the 144 day-old foetus.

Injection of luteinizing hormone releasing hormone in quantities ranging from 25 to 150 μg caused no changes in circulating levels of TSH and prolactin.

It is concluded that although the foetal pituitary can respond to TRH by at least 107 days gestation, its maturity in relation to prolactin synthesis and release develops gradually, but most rapidly over the last 10 days of gestation. In comparison, the pituitary-thyroid system, known to be functioning before 107 days, may be insensitive to hypothalamic control. The evidence suggests that there is increased maturity of the thyroid gland with increasing foetal age, the concomitant rise in thyroid hormones initiating a negative feedback response.
TWO ABNORMALITIES OF GLUCOSE-INDUCED INSULIN SECRETION: DOSE-RESPONSE CHARACTERISTICS AND INSULIN SENSITIVITY
Authors: Turner R. C. , Harris E. , Ounsted M. , Ponsford C.
Published: December 2008

To characterize the defect of insulin secretion in diabetes, the response to different iv glucose loads has been studied in women who have had gestational diabetes and are, by definition, latent diabetic (LD). Women who have produced a large-for-dates baby, but who were not known to have been diabetic (LFD), have been investigated to determine if they have abnormal metabolism. Both groups were found to have raised fasting plasma glucose concentrations. Only the LD had glucose intolerance, which was associated with a reduced first phase insulin response to all glucose loads with a decreased maximal secretory capacity (low V max). The LFD women appeared to include a distinct abnormality in which the β cells had decreased sensitivity to glucose (high Km), with diminished secretory response to small but normal response to large loads. Whereas the LD probably have disordered μ cell function, some of the LFD women may represent the upper end of the normal range of the glucose "set" of β cell function. Neither group had insulin resistance, as measured by the hypoglycaemic response to an iv insulin bolus. A woman who has produced a LFD, but who was not known to be diabetic, does not necessarily have a diabetic tendency.
INHIBITORY EFFECT OF SOMATOSTATIN ON INSULIN SECRETION DURING α-ADRENERGIC BLOCKADE IN THREE DIFFERENT SPECIES
Authors: Järhult Johannes , Ahrén Bo , Lundquist Ingmar
Published: December 2008

It has recently been suggested from experiments in dogs that somatostatin suppresses insulin release via a stimulation of the inhibitory α-adrenoceptors of the pancreatic B-cell. The effect of somatostatin on insulin secretion during α-adrenergic blockade with phentolamine was therefore studied in three different species; the rat, the cat and the mouse.

It was found that somatostatin significantly depressed insulin release during α-adrenoceptor blockade in all three species. In the rat, infusion of somatostatin at a dose of 0.3 μg/kg/min decreased basal plasma insulin concentration by 92 %. In the presence of phentolamine, the same dose of somatostatin lowered plasma insulin by 85 %. In the cat, a similar infusion of somatostatin lowered basal plasma insulin concentration by 87 %, but its depressive effect during α-adrenergic blockade was comparatively less pronounced (68 %) than in the rat. In the mouse, a single iv injection of somatostatin induced a short-lasting depression of plasma insulin concentration during α-adrenergic blockade.

From these results it seems unlikely that somatostatin should inhibit insulin release simply by stimulation of α-adrenoceptors on the B-cell. It cannot be ruled out, however, that a more complex interaction exists between somatostatin and the sympatho-adrenal system with regard to the control of insulin secretion.
CHANGES IN PLASMA ALDOSTERONE FOLLOWING THE ADMINISTRATION OF VARIOUS COMBINATIONS OF STIMULI
Authors: Gaillard R. C. , Riondel A. , Merkelbach U. , Vallotton M. B.
Published: December 2008

The effects on plasma aldosterone levels of combinations of the main factors involved in aldosterone regulation have been studied in normal young male subjects. These factors, namely K, angiotensin II and ACTH were studied using combinations of K+ with angiotensin II, K+ with ACTH, and angiotensin II with ACTH.

KC1 infused in amounts (5–10 mEq./h) insufficient to increase plasma aldosterone by itself was found to potentiate the aldosterone response to an infusion of angiotensin II (7 ng/kg/min) in 8 out of 13 subjects. The same amount of KCl was also found to increase the rise in plasma aldosterone following an infusion of ACTH (16 ng/kg/min).

When an angiotensin II infusion was superimposed on the last 2 h of a 4-h infusion of ACTH, a striking rise in plasma aldosterone was observed, which exceeded the values obtained by ACTH alone. Conversely, when an ACTH infusion was superimposed on the last 2 h of a 4-h angiotensin II infusion, a further increase of plasma aldosterone was again observed. Our data support the idea that changes in all the known stimuli of aldosterone secretion have to be taken into account when interpreting changes in plasma aldosterone. Thus KCl, infused at rates without effect on aldosterone when given alone, will increase aldosterone during angiotensin II or ACTH infusion. The data also demonstrate that no refractory period is observed when one stimulus is superimposed on a previous one.
PLASMA 1,25-DIHYDROXYVITAMIN D LEVELS IN PREGNANCY AND LACTATION
Authors: Lund Bjarne , Selnes Anders
Published: December 2008

Plasma concentrations of 1,25-dihydroxyvitamin D (1,25–(OH)2D), serum prolactin and serum parathyroid hormone (PTH) were followed during pregnancy and lactation in 16 women.

High 1,25–(OH)2D was demonstrated in human pregnancy and lactation. A causative relationship between 1,25–(OH)2D and prolactin is discussed and a possible explanation of the mechanism of the augmented calcium absorption in human pregnancy and lactation is suggested.
ISOLATION, CHARACTERIZATION AND RADIOIMMUNOASSAY OF CORTICOSTEROID-BINDING GLOBULIN (CBG) IN HUMAN SERUM – CLINICAL SIGNIFICANCE AND COMPARISON TO THYROXINE-BINDING GLOBULIN (TBG)
Authors: Bernutz C. , Hänsle W. O. , Horn K. , Pickardt C. R. , Scriba P. C. , Fink E. , Kolb H. , Tschesche H.
Published: December 2008

Isolation of the corticosteroid-binding globulin CBG was achieved by 5 chromatographical steps on cortisol Sepharose, QAE-Sephadex A-50, Con A-Sepharose and hydroxylapatite. The purity of the isolated CBG was demonstrated in polyacrylamide gel electrophoresis, SDS electrophoresis, immunodiffusion and ultracentrifugation. Microheterogeneity was shown in isoelectric focusing by 5 bands in the pH range of 3.7–4.2, which could be reduced to one major band after neuraminidase treatment. The equimolar binding of cortisol to CBG was demonstrated by binding studies. The association constant for cortisol was 2.8 × 108 m−1, for progesterone 1.7 × 106 m−1. From analytical ultracentrifugation, the molecular weight was calculated on 50 700; the sedimentation coefficient was 3.6 S, the partial specific volume 0.690 ml/g, the Stokes radius 38 Å and the frictional coefficient ratio 1.5.

A specific radioimmunoassay for CBG was established using the purified CBG for immunization, radioiodination and for calibration standards. The normal range of CBG levels in human serum was 2.4–4.4 mg/100 ml (mean ± 2 sd). Studies were performed to compare the levels of CBG and thyroxine-binding globulin (TBG). No sex differences but a significant biphasic age dependence were observed for both proteins. In pregnancy and under oestrogen treatment of women and men, CBG was demonstrated to be the more distinct indicator of oestrogenic activity as compared with TBG, whereas the sensitivity of TBG was more pronounced to supposedly antioestrogenic substances like Danazol, and in severe disease. No coincidence of genetic CBG and TBG deficiencies have been found so far.
SERUM LEVELS OF SOMATOMEDIN A AND GROWTH DURING LONG-TERM TREATMENT OF PATIENTS WITH PITUITARY DWARFISM WITH HUMAN GROWTH HORMONE
Authors: Takano Kazue , Hizuka Naomi , Shizume Kazuo , Hasumi Yoko
Published: December 2008

Eighteen patients with pituitary dwarfism were treated for 1 7/12 to 6 years with human growth hormone (hGH) at a dose of 0.19–0.62 unit (U) per kg of body weight per week. The mean increment in height was 2.0 ± 0.4 and 8.8 ± 0.5 cm/year before and the first year after treatment of hGH, respectively.

A significant positive correlation was observed between serum levels of somatomedin A and growth rate, especially in children with bone age below 10 and a duration of treatment of less than one year (r = 0.66, P < 0.005). Long-term treatment with hGH was accompanied by a decreasing response. However, the serum levels of somatomedin A did not decrease significantly. Therefore, decreased growth increment in these situations was not due to decreased serum levels of somatomedin A.
A TSH SECRETING PITUITARY TUMOUR CAUSING HYPERTHYROIDISM: PRESENTATION OF A CASE AND REVIEW OF THE LITERATURE
Authors: Afrasiabi Ali , Valenta Lubomir , Gwinup Grant
Published: December 2008

A 45 year old male with a 12 year history of mild hyperthyroidism and a pituitary tumour is presented. He had both clinical and laboratory evidence of hyperthyroidism and his serum TSH was persistently and markedly elevated. A TRH test resulted in no further rise in serum TSH. No evidence of pituitary or peripheral endocrine deficiencies existed and prolactin levels were normal. Craniotomy was performed and a pituitary adenoma was removed. On light microscopy, it was mostly composed of chromophobes. However, occasional granulated cells were observed, and on electron microscopy, most of the cells contained fine granules, which suggested possible thyrotroph origin of the tumour. One week post-operatively the patient's serum TSH returned to normal. Again, TRH produced no response in TSH. The patient became hypothyroid by clinical and laboratory findings and is currently on thyroid replacement therapy. The previously reported TSH secreting tumours associated with hyperthyroidism are reviewed.
EFFECTS OF THREE-DAY ORAL CHOLECYSTOGRAPHY ON SERUM IODOTHYRONINES AND TSH CONCENTRATIONS: COMPARISON OF THE EFFECTS AMONG SOME CHOLECYSTOGRAPHIC AGENTS AND THE EFFECTS OF IOPANOIC ACID ON THE PITUITARY-THYROID AXIS
Authors: Suzuki Hoji , Kadena Nariyuki , Takeuchi Keisuke , Nakagawa Shoichi
Published: December 2008

The effects of repeated doses of oral cholecystographic agents on serum thyroxine (T4), 3,3′,5-triiodothyronine (T3), 3,3′,5′-triiodothyronine (rT3) and thyrotrophin (TSH) concentrations were studied in 37 euthyroid male subjects.

Iobenzamic acid, tyropanoic acid, iopanoic acid, and ipodate sodium, in a dosage of 3 g for 3 days, respectively, induced a significant decrease in serum T3 and an increase in rT3 within 24 h after the initial dose, followed by an increase in TSH and a slight increase in T4. The extent of the changes in rT3 varied between the agents, ipodate causing the greatest change, but without any relation to the changes in T3 or T4.

Responses of serum T4, T3, rT3 and TSH concentrations to exogenous thyrotrophin-releasing hormone (TRH) and bovine TSH were also studied before and after 3-day doses of iopanoic acid. In 11 subjects given iopanoic acid, the response of TSH to TRH (500 μg, iv) was increased but the T3 response was unchanged. A dose of TSH (10 U.S.P. units, im) caused a significant increase in serum T3 and a decrease in TSH concentrations in 5 subjects both before and after cholecystography.

It is thus suggested that in euthyroid subjects given multiple doses of oral cholecystographic agents, (1) the primary and consistent events are the reciprocal changes of serum T3 and rT3. although the extent of the changes is not coordinately reciprocal; (2) the responsiveness of the pituitary thyrotrophs and thyroid to TRH is preserved; and (3) the high basal and TRH-induced TSH in the serum may be ascribed to the decrease in the serum T3 concentration.
SOLUBILIZATION AND PARTIAL CHARACTERIZATION OF THYROID MEMBRANE TSH BINDING PROTEINS
Authors: Czarnocka B. , Nauman J. , Adler G. , Kiełczyński W.
Published: December 2008

Crude plasma membranes obtained from bovine thyroids were found to possess one class of high affinity, low capacity binding sites for TSH with average association constant (Ka) of 1.301 × 109 m−1 and maximal capacity 8.76 × 10−10 m/mg of protein.

Treatment of crude membranes fraction with 0.1 % Triton X-100 and the subsequent sonication in ultrasonic disintegrator resulted in solubilization of membranes proteins with mean recovery of 40.0 ± 6.2 %. Soluble proteins retained the property to bind [125I]TSH, but the binding of the hormone was decreased.

The removal of the detergent from the solubilizate by gel filtration on Sephadex LH-20 increased the binding of TSH well above that demonstrated for crude thyroid membranes.

The chromatography of soluble proteins on Ultrogel AcA-44 revealed the presence of two TSH binding proteins, one with the molecular weight (m.w.) above 130 000 daltons and the other with the m.w. approximately 30 000 daltons.

The electrofocusing of solubilizate on Ampholine resulted in two protein peaks, one at pH 4.0–4.1 and the other at pH 4.4–4.6. The latter peak was shown to bind [125I]TSH specifically.

The present results have confirmed the heterogeneous character of solubilized TSH receptor preparation and have shown that the hormone binding sites belong to acid proteins.
INTERACTION OF SYNTHETIC PROGESTAGENS WITH RENAL MINERALOCORTICOID RECEPTORS
Authors: Wambach G. , Higgins J. R. , Kern D. C. , Kaufmann W.
Published: December 2008

Progesterone increases urinary sodium excretion at least in part by competition for renal mineralocorticoid receptors. In contrast, synthetic progestagens do not increase sodium excretion or even cause a slight sodium retention. We therefore compared the ability of progesterone and 12 progesterone like compounds to displace [3H] aldosterone from binding at cytoplasmic mineralocorticoid receptors in rat kidney. All synthetic progesteronelike steroids were less active than progesterone in competing with [3H]aldosterone for the receptor binding: progesterone 100 %, 11β-OH progesterone 50 %, 17 a OH-progesterone 24 % and 16 α-methylprogesterone 3 %. Derivates of 17 α OH-progesterone (medrogestone 5 %, dydrogestone 4 %, medroxy progesterone-acetate 2 % and chlormadinone-acetate 0.5 %) were more potent than 19-nor-testosterone derivates: ethisterone 1 %, norethisterone < 1 %, norethindrone < 1 %, norethylnodrel < 1 %, and ethynodiol-diacetate < 1 %. The decreased affinity of synthetic progestins for mineralocorticoid receptors explains in part the lack of natriuretic activity of these compounds.
STUDIES ON A PROTEIN SYNTHESIS DEPENDENT STEP IN LH RELEASE BY LH-RH
Authors: de Koning J. , van Dieten J. A. M. J. , Tijssen A. M. I. , van Rees G. P.
Published: December 2008

The hypothesis that LH-RH induces LH release partly through a protein synthesis dependent step (protein factor) was further investigated using two different experimental designs.

First, during incubation of pituitary glands of intact dioestrous female rats with a maximally active concentration of LH-RH, the inhibitor of protein synthesis cycloheximide was added at various times after the beginning of the incubation. The results show that it takes a relatively long time, i.e. more than 1 h of exposure to LH-RH before the amount of the protein factor has increased sufficiently to allow a maximal LH secretion.

Secondly, LH-RH was injected iv after which the protein factor was assayed by incubating the pituitary glands with a maximally active concentration of LH-RH in the presence of cycloheximide and measuring LH release in vitro. It was found that 1 h after the injection sufficient protein factor was present to permit an elevated response to LH-RH. This response could be suppressed by injecting cycloheximide prior to LH-RH. When the interval between injection of LH-RH and beginning of the incubation was increased to 2 h, LH release in vitro decreased again. However, ovariectomy immediately before LH-RH injection resulted in maintenance of the elevated response to LH-RH in vitro, indicating a role of the ovaries in this phenomenon.
THE EFFECT OF RITODRINE ON CARBOHYDRATE AND LIPID METABOLISM IN NORMAL AND DIABETIC PREGNANT WOMEN
Authors: Lenz Suzan , Kühl Claus , Wang Palle , Mølsted-Pedersen Lars , Orskov Hans , Faber Ole K.
Published: December 2008

The metabolic effects of a one hour intravenous infusion of the β-2-receptor stimulating drug ritodrine were studied in seven normal pregnant women, three White class A pregnant diabetics and eight White class B-D pregnant diabetics.

During ritodrine infusion all subjects in the three groups exhibited increases in plasma glucose (1.0, 1.6 and 2.1 mmol/l respectively), free fatty acids (360, 850 and 1150 μmol/l), lactate (0.43, 0.80 and 0.86 mmol/l) and β-hydroxybutyrate and decreases in standard bicarbonate. The rise in plasma glucose, free fatty acids and lactate was more pronounced in insulin treated diabetic. The rises in β-hydroxybutyrate and decreases in standard bicarbonate were of the same magnitude in all three groups. Plasma potassium fell in all subjects, whereas no detectable changes in plasma sodium were observed.

The endocrine pancreatic function was assessed by measuring plasma insulin (White class A and normals), C-peptide (White class B-D) and glucagon (all subjects). Plasma insulin increased in normals (22 μIU/ml) and White class A diabetics (33 μIU/ml), whereas plasma C-peptide of the insulin treated patients (White class B-D) were below measurable concentrations. Plasma glucagon and cortisol concentrations were not influenced by ritodrine.

The results suggest that the diabetogenic changes induced by ritodrine are augmented with the severity of diabetes but not ascribable to a diabetes-like change in the function of the endocrine pancreas.
SOLUBILIZATION OF THYROXINE-5′-DEIODINASE ACTIVITY FROM RAT LIVER MICROSOME FRACTION
Authors: Takaishi Masaru , Shimizu Taeko , Shishiba Yoshimasa
Published: December 2008

The greater part of T3 is converted from T4 in liver or kidney. The majority of this activity exists in microsomal fraction. In the present study, we investigated whether this activity can be solubilized from rat liver microsomal pellet with various concentrations of deoxycholate (DOC). The extent of solubilization was compared with that of protein, rotenone insensitive NADH cytochrome c reductase or NADH cytochrome b5 reductase, which have been shown to associate with microsomal membrane rather than luminar contents. When 0.05 % of DOC which was capable of releasing luminar contents of microsomal vesicles was applied to microsomal suspension, only a limited part of NADH cytochrome b5 reductase, rotenone insensitive NADH cytochrome c reductase or T4-5′-deiodinase activity was solubilized. When the concentration of DOC was increased to 0.125 %, 41 % of T4-5′-deiodinase activity was solubilized. Solubilization of protein, NADH cytochrome b5 reductase or rotenone insensitive NADH cytochrome c reductase was increased abruptly to 66 %, 58 % or 63%, respectively. The highest specific activity was obtained at 0.125% DOC. These results suggest that the T4-5′-deiodinase is associated with microsomal membrane instead of luminar contents.
RESPONSES OF ALDOSTERONE-PRODUCING ADENOMAS TO ACTH AND ANGIOTENSINS
Authors: Saruta Takao , Okuno Tetsuji , Eguchi Toyohisa , Nakamura Ryuichi , Saito Ikuo , Kondo Kazuoki , Oka Masatsugu , Matsuki Shun
Published: December 2008

To elucidate the control mechanism of aldosterone production in primary aldosteronism, in vivo and in vitro studies were done in 7 patients with aldosterone-producing adenomas.

In the in vivo study, plasma aldosterone was stimulated more significantly by synthetic ACTH than by angiotensin II or furosemide. Diurnal variations of plasma aldosterone, which were studied in 4 patients, were similar to those seen in normal controls. In agreement with the results in the in vivo study, the in vitro study also revealed ACTH stimulated aldosterone and deoxycorticosterone (DOC) from the adenoma more markedly than angiotensin II or III. There was no adenoma which was more sensitive to angiotensin II or III than to ACTH. From these results it is considered that changes in plasma aldosterone induced by the exogenous administration of angiotensin II or ACTH in patients with aldosterone-producing adenoma are mainly based on changes in aldosterone production in the adenoma. Furthermore, in patients with an aldosterone-producing adenoma in whom diurnal variations of plasma aldosterone similar to those in normal subjects are observed, responses of aldosterone to angiotensin II are supposed to be less than those to ACTH.
Repetitive intravenous TRH-stimulations at short intervals in euthyroid and hypothyroid subjects
Authors: Ahuja S. , Baumgarten S. , Oeff K.
Published: December 2008

In 17 euthyroid normal volunteers and 17 hypothyroid patients, serum concentrations of TSH, T3 and T4 were measured after multiple stimulations with TRH. All subjects received 6 TRH-injections (200 μg iv) at intervals of 2 h. Three euthyroid normal volunteers were stimulated 12 times with TRH in the same way.

The TSH response (ΔTSH) was significantly decreased (P<0.01) after the 4th injection, and after the 5th of 6th stimulation, it was significantly raised (P<0.02) compared with the 4th. In the case of the 12-fold stimulations, the ΔTSH also rose after the 9th or 10th injection compared with the response after the 8th of 9th.

In 5 of the 17 normals, the increase in ΔTSH observed after the 5th or 6th TRH-injection was greater than the ΔTSH after the first stimlation.

Serum T3 and T4 levels rose already after the first TRH-stimulation (P<0.01) and remained at these increased levels thereafter.

The hypothyroid patients also showed initial decrease of ΔTSH (P<0.01). The increase of the TSH-response to TRH, however, was observed after the 4th TRH-injection (P<0.05) rather than after the 5th or 6th, followed by another decrease of ΔTSH after the 5th stimulation (P = 0.02). In 11 of the 17 hypothyroid patients, there was a second increase of ΔTSH after the 6th TRH-stimulation. This second increase was greater than the first in 10 of the 11 subjects. Serum T3 and T4 levels in the hypothyroid subjects remained unchanged during the entire examination period.

From these results, it can be concluded that the cause for the TSH response pattern in TRH-stimulations repeated at brief intervals cannot be due to the feed-back of thyroid hormones, but rather to the activity of TSH-producing pituitary cells.
The International Reference Preparation of Calcitonin, Human, for Bioassay: Assessment of material and definition of the International Unit
Authors: Das Rose E. Gaines , Zanelli Joan M.
Published: December 2008

An international reference material is required for bioassays of preparations of synthetic human calcitonin for administration to man and for use in immunoassays.

A preparation of synthetic human calcitonin in ampoules coded 70/234 (previously widely used as the MRC Research Standard) has been examined in an international collaborative study involving 7 laboratories in 6 countries. The results of 34 in vivo bioassays with two other preparations of synthetic human calcitonin showed that this preparation was suitable to serve as a standard.

With the agreement of the participants in the collaborative study, the batch of ampoules, code 70/234, was established in 1978 by the World Health Organization as the International Reference Preparation of Calcitonin, Human, for Bioassay. The International Unit of human calcitonin was defined as the activity contained in one ampoule of this preparation, thus maintaining continuity of the unit of the research standard.
Ethanol inhibition of insulin secretion by perifused rat islets
Authors: Singh Sant P. , Patel D. G. , Snyder Ann K.
Published: December 2008

In vivo and in vitro effects of ethanol on the kinetics of insulin secretion in response to glucose and tolbutamide were studied in perifused rat islets. Phases I and II insulin response to 16.7 mm glucose was decreased 46% and 48%, respectively, in islets of rats given ethanol intragastrically 1 g/kg 1 h prior to sacrifice. Mean blood ethanol levels at the time of animal sacrifice were 19.4 mmol/l. The magnitude of insulin suppression was not significantly enhanced with higher ethanol doses, 2 or 3 g/kg, although mean blood ethanol levels increased to 25.9 and 60.3 mmol/l, respectively. Similarly, significant inhibition of both phases of insulin response to glucose occurred when ethanol 1 or 3 g/kg was given intraperitoneally instead of orally. Ethanol had no effect on insulin secretion when given orally 4 h instead of 1 h prior to islet isolation.

Ethanol, 65 mmol/l, added directly to rat islets perifusate simultaneously with 16.7 m m glucose decreased both phases I and II insulin response nearly half; whereas addition of 21.7 instead of 65 mmol/l ethanol had no effect. Pre-treatment of islets with 21.7 or 65 mmol/l ethanol during 30 min basal islets perifusion period had no effect on subsequent insulin response to 16.7 mm glucose. Insulin response to 10 mm tolbutamide was decreased nearly 81% by the simultaneous presence of 65 mmol/l ethanol in islets perifusate.
Properties of partially purified thymidine kinase in adrenal tissue of hyperplasia, adenomatous hyperplasia, adenoma and carcinoma of patients with Cushing's syndrome.
Authors: Nawata Hajime , Kato Ken-ichi , Ibayashi Hiroshi
Published: December 2008

Thymidine kinase (TK) was partially purified from adrenal tissues with adrenocortical hyperplasia, adenomatous hyperplasia, adenoma and carcinoma from patients with Cushing's syndrome and from normal adrenal glands. Adrenocortical carcinoma, adenoma, hyperplasia and nodule and hyperplastic portion of adenomatous hyperplasia contained higher concentration of TK than normal adrenal gland. By DEAE-cellulose column chromatography, adrenocortical carcinoma gave two peaks (Peak I and Peak II) of TK, while in other adrenal tissues the second peak (Peak II) was only slightly detected or hardly detected. TK in all these tissues was identical with respect to pH optimum, metal requirement and inhibition by dTTP. dCTP inhibited TK activities of normal adrenal gland and the hyperplastic portion of adenomatous hyperplasia by 55%, respectively, but hardly affected the activity of the nodule of adenomatous hyperplasia, adenoma, hyperplasia and carcinoma. TK from hyperplastic portion of adenomatous hyperplasia showed the intermediate heat stability between the heat-stable enzyme from normal adrenal gland and the heat-labile enzyme from adrenocortical carcinoma, adenoma, hyperplasia and the nodule of adenomatous hyperplasia. The apparent Km for thymidine from adenocortical carcinoma (Peak I and Peak II) was 5.0 and 11.1; adenoma, 4.8; hyperplasia, 5.5; adenomatous hyperplasia (nodule, 5.0 and hyperplastic portion, 19.8) and normal adrenal gland, 25.0 μm.

These observations indicated that TK with different catalytic properties existed in various human adrenal tissues. They also demonstrated that TK isolated from the nodule of adrenocortical adenomatous hyperplasia had similar properties as adrenocortical adenoma, while TK from the hyperplastic portion had the intermediate catalytic properties between normal adrenal gland and adrenocortical hyperplasia.
Studies on changes in the concentration of serum adrenal androgens in pubertal twins
Authors: Akamine Yasuo , Kato Ken-ichi , Ibayashi Hiroshi
Published: December 2008

A cross-sectional study was undertaken to investigate the correlation of the level of serum adrenal androgens with clinical signs of puberty and to assess the participation of genetic factors in the onset and progression of puberty. Serum concentrations of 11-deoxy-17-ketosteroids (11-deoxy-17-KS), dehydroepiandrosterone (DHEA) and androstenedione (4-A-dione) were measured in 74 monozygotic and 24 dizygotic twin pairs during the years of puberty. The mean serum concentrations of the adrenal androgens increased significantly with the advancement of bone age. A comparison of the adrenal androgen concentrations at a bone age of 15 years revealed the trend of earlier progression of puberty in girls than in boys. Serum 11-deoxy-17-KS and DHEA levels correlated fairly well with the stages of pubic and axillary hair growth in both sexes. No correlation of adrenal androgen levels with pituitary gonadotrophins or prolactin was observed in either sex during puberty. These results strongly suggest the importance of the specific action of adrenal androgens on the onset and progression of puberty, and further suggest that the maturation of the hypothalamic-pituitary-gonadal axis is not involved primarily in the maturation of the adrenal cortex during puberty.

From the viewpoint of twin zygosity, intra-pair differences of serum adrenal androgen levels were compared between monozygotic and dizygotic pairs of twins. Serum 11-deoxy-17-KS and 4-A-dione levels in monozygotic pairs of twins showed a significantly higher intrapair similarity than in dizygotic pairs of twins. These findings suggest that during puberty the maturation of the adrenal cortex is regulated by genetic factors.
Thyroid-pituitary function in eight anencephalic infants
Authors: Grasso S. , Filetti S. , Mazzone D. , Pezzino V. , Vigo R. , Vigneri R.
Published: December 2008

The function of the thyroid pituitary axis was investigated in 8 anencephalic infants with no hypothalamus.

Thyrotrophin (TSH), thyroxine (T4), 3,5,3′-triiodothyronine (T3) and 3,3,′5′-triiodothyronine (reverse T3, rT3) were measured in the cord blood in 5 cases and during the first 4 h of life in 3 cases, TSH response to synthetic thyrotrophin-releasing hormone (TRH) (200 μg iv) was carried out in two cases and thyroid hormone response to bovine TSH (5 IU iv) was evaluated in 3 cases.

The following results were obtained:

1) The pituitary gland was found in all infants and the thyroid was normal both grossly and by microscopic sections.

2) TSH levels at birth were normal but there was no spontaneous post-delivery surge.

3) T4 and T3 values at delivery were within normal range, but no T3 increase was present after birth. rT3 levels at birth were higher than normal in 3 cases.

4) Administration of TRH caused a marked and rapid TSH release.

5) Thyroid hormone response to TSH was normal.

The present findings suggest that in the anencephalic foetus both pituitary TSH-secreting cells and the thyroid gland do develop despite the absence of the hypothalamus and are able to function if adequately stimulated.
The effect of glucagon and prostaglandin E1 on cyclic AMP levels in liver of heat exposed hamsters
Authors: Aharon Miriam , Graziani Yosef , Chayoth Reuben
Published: December 2008

Cyclic AMP levels in liver slices of hamsters exposed to 35°C for 21 days and controls maintained at 22°C was found to be similar in basal conditions. Glucagon (10 μg/ml) caused 3.5 times elevation of cyclic AMP levels in control hamsters and 9 times elevation in 35°C exposed hamsters, thus a difference of 150% of the nucleotide concentration was found between the two experimental groups. When 10−2m theophylline was added, the cyclic AMP levels were 80% higher in 35°C exposed hamsters both in the presence and absence of 10 μg/ml glucagon.

The difference between controls and heat exposed animals was found to be the same when various concentrations of both glucagon or prostaglandin E1 were added to the liver slices.

Adenylate cyclase activity was similar in both experimental groups, while low Km phosphodiesterase was significantly less active in the liver of 35°C exposed animals when compared to the controls.
Cushing's syndrome due to unilateral nodular adrenal hyperplasia: a new pathophysiological entity?
Authors: Josse Robert G. , Bear Robert , Kovacs Kalman , Higgins H. Patrick
Published: December 2008

A case is presented of a 43-year-old Caucasian female with Cushing's syndrome, malignant hypertension and renal insufficiency. Plasma cortisol values were elevated (19.5 μg/100 ml at 0800 h and 18.5 μg/100 ml at 2200 h) with loss of diurnal variation and failure of suppression with low and high dose dexamethasone. 17-ketogenic steroid excretion remained unchanged after metyrapone administration. Adrenal vein plasma cortisol values showed prominent left-sided gradient. Gross, histologic and electron-microscopic examination of the left adrenal gland revealed changes of nodular adrenal hyperplasia. The presence of a suppressed right adrenal gland was confirmed post-operatively by a five day ACTH infusion. This case may represent a previously unreported variant of Cushing's syndrome due to unilateral nodular adrenal hyperplasia.
Ontogeny of somatostatin in the human gastro-intestinal tract, endocrine pancreas and hypothalamus
Authors: Chayvialle J. A. , Paulin C. , Dubois P. M. , Descos F. , Dubois M. P.
Published: December 2008

The appearance, time and distribution of somatostatin in the pancreas, gastro-intestinal tract and hypothalamus were studied comparatively in human foetuses aged 6–32 weeks, by immuno-cytochemistry and radioimmunoassay. Somatostatin was detected by both methods in all segments including the colon. The first cells were observed, and somatostatin was present in measurable amounts at 8 weeks in pancreas, duodenum and intestine, while the peptide was detected at 12 weeks in antrum and colon, at 14 weeks in fundus, and at 16 weeks in hypothalamus. Subsequently, the largest cell population was located in the pancreas, where peptide concentration and age were positively correlated (P < 0.01, r = 64). From 15 to 21 weeks of age, the mean somatostatin concentration in pancreas (12.4 ± 1.84 ng/mg) was clearly higher than in hypothalamus (0.05 ± 0.02 ng/mg) or in any segment of the gut, where values ranged from 0.36 ± 0.06 (fundus) to 4.74 ± 0.83 ng/mg (duodenum). The early appearance time of somatostatin, and its specific distribution with preferential location in the pancreas, suggest that the peptide may play a major role for the development of the foetal digestive tract, and that it may be involved in the regulation of other endocrine secretions, especially in the pancreas.
Plasma LH levels following electrochemical stimulation of the deafferented medial basal hypothalamus
Authors: Carrillo A. J. , Hagino N. , Setalo G.
Published: December 2008

We have investigated the capability of a completely deafferented medial basal hypothalamus (MBH) pituitary complex to support LH release following electrochemical stimulation (ECS) of the arcuate-median eminence (ARC-ME) region. In adult female rats the MBH was completely deafferented (CD) on the morning of pro-oestrus (08.00-10.00 h of day 0). In the first experiment the animals were divided into 5 groups depending on the day of ECS (14.00–16.00 h) and oestradiol benzoate (Oe) treatment (08.00–10.00 h): group No. 1) ECS on day 0; 2) no ECS; 3) ECS on day 1; 4) Oe on day 0 and ECS on day 1; 5) Oe on day 4 and ECS on day 5. Blood samples were collected from the external jugular vein under ether anaesthesia for LH determinations just before and 1 and 2 h after ECS. ECS on day 0 resulted in a significant (P<0.01) rise in plasma LH at 1 and 2 h, while the rats subjected to CD, but not ECS failed to show any changes in plasma LH levels. ECS on days I and 5 (groups 3 and 5) failed to alter plasma LH levels, however, ECS on day 1 in Oe treated rats produced a significant (P < 0.01) elevation in plasma LH that was comparable to that of day 0. In a second experiment Oe was injected on days 1–5 and ECS of the ARC-ME was done bilaterally. ECS on day 5 resulted in a significant (P < 0.05) rise in plasma LH levels in rats with a completely deafferented MBH. In animals with an incomplete deafferentation ECS resulted in a much greater (P < 0.005) rise in plasma LH at l and 2 h. Since LH was released several days after complete hypothalamic deafferentation, these data suggest that LRH secreting cells may be present within the MBH of the rat. In a third experiment injection of LRH (400 ng) on days 0, 1 and 5 with Oe on days 0, 4 or 1–5 resulted in a significant (P < 0.001) rise of plasma LH at 30 and 60 min in all groups. Rats injected on day 0 showed the greatest elevation at 60 min in all groups. Saline injected rats did not show any changes in plasma LH levels.
The influence of raphe nucleus lesions on fertility in the female rat
Authors: Waloch W. , Szreniawski Z.
Published: December 2008

By lesioning brain raphe nuclei, the effect of decreasing the activity of the serotoninergic (5-HT) system on the fertility of the female rat was investigated. The females were mated on the 10th day after lesioning. On both the 15th and 21st day of pregnancy the numbers of live and resorbed foetuses and the weights of placentas in the lesioned groups did nor differ statistically as compared with the control group. Interestingly, the lesioned group showed an increase in the number of ovulating cells on the one hand, and decrease in the number of implantations on the other. The data obtained strongly suggest that midbrain serotoninergic cell groups (B7, B8) inhibit ovulation and are not associated with initiation of labour in the female rat.
Effects of propranolol and atenolol on plasma and urinary cyclic adenosine 3′,5′-monophosphate in hyperthyroid patients
Authors: Nilsson Ove R. , Andersson Rolf G. G. , Karlberg Bengt E.
Published: December 2008

Supine and upright plasma concentrations and the urinary excretion of cyclic adenosine 3′,5′-monophosphate (cAMP) were studied in 26hyperthyr oid patients before and during treatment for 3–6 days and one month with a non-selective (propranolol, n = 13) or a selective β-l-adrenergic antagonist (atenolol, n = 13). Before treatment supine and upright plasma concentrations of cAMP were elevated compared to healthy controls and compared to a re-investigation in the euthyroid state. Propranolol and atenolol both reduced supine and upright plasma cAMP and the reduction persisted during one month of treatment. In five untreated hyperthyroid patients no changes in plasma cAMP were observed between two different investigations. Turning to an upright posture was associated with an increase in plasma cAMP levels in 22 out of the 31 hyperthyroid patients (P < 0.05), while all 11 patients re-examined in the euthyroid state showed a rise in plasma cAMP in the upright position (P < 0.001). The 24 h urinary excretion of cAMP was unaltered during treatment with β-adrenergic antagonists.

The data support earlier findings of stimulation of adrenergic receptor activity by thyroid hormone excess. In hyperthyroidism β-adrenergic antagonists decrease but do not normalize the activity of the adenylate cyclase system. This reducing effect may be of importance for the alleviation of hyperthyroid symptoms and signs during treatment with β-adrenergic antagonists.
Clofibrate and a related compound suppress TSH secretion in primary hypothyroidism
Authors: Kobayashi Isao , Shimomura Yohnosuke , Maruta Sakae , Ohshima Kihachi , Mori Masatomo , Kamio Nobuyuki , Fukuda Hitoshi
Published: December 2008

A single oral dose of the hypolipidaemic agent ethyl-p-chlorophenoxyisobutyrate (clofibrate, 750 mg) produced a significant reduction on the high basal serum TSH level in patients with primary hypothyroidism. There was no consistent change in serum levels of thyroxine-iodine (T4-I), triiodothyronine (T3) and per cent free T4 (%FT4) during the study. On the other hand, clofibrate failed to produce discernible changes in the basal and TRH-induced TSH secretion in euthyroid subjects. Similar results were also obtained with the centrally active drug meclofenoxate hydrochloride (MH, 750 mg, drip infusion), similar in structure to clofibrate. These findings suggest that clofibrate and MH inhibit TSH secretion in patients with primary hypothyroidism, possibly by a direct action at the hypothalamic or pituitary level.
Intrafollicular re-cycling of organic iodine in the hypophysectomized rat as observed by a long-term kinetic study
Authors: Bastiani Paul , Simon Claude , Penel Claude
Published: December 2008

A long-term kinetic study was started 8 days after hypophysectomy in rats previously adapted to receive 5 μg iodide daily, and maintained on the same diet after surgery. At each time, the renewed fraction for thyroglobulin (Tg) and lysosomes in the gland, and hormones in the plasma was calculated by the method of isotopic equlibrium.

All the pools studied are renewed very slowly, but with different kinetics. Between time zero and the 25th day of the experiment, the renewed fraction in plasma hormones always exceeds that of Tg. Thus, in hypophysectomized rats, Tg pool is composed of at least two compartments with different turn-over rates. Tg molecules of both compartments are endocytosed, but that of the faster compartment participate in secretion in a preferential way.

Peeling of the data for the 60-day period of experiment confirms these results. In addition, peeling demonstrates a 15-day delay in the turn-over of the second compartment. Such a delay was not found in the turn-over of this compartment in lysosomes. Thus, we may again postulate, in hypophysectomized rats, a recycling of iodine in organic form from the lysosomes back to the luminal colloid, as previously proposed for control rats.
Pancreatic glucagon response to glucose in hyperlipoproteinaemia with and without abnormalities in carbohydrate metabolism
Authors: Ratzmann K. P. , Schulz B. , Witt Sabine , Ziegler M. , Heinke P.
Published: December 2008

The pancreatic glucagon (IRG) and insulin (IRI) secretion patterns were studied in 19 normal weight healthy male subjects without a family history of diabetes, and in 24 male patients with endogenous hyperlipoproteinaemia, by means of a 2 h-glucose infusion (12 mg/kg/min) primed by an initial injection of 0.33 g/kg. The hyperlipoproteinaemic group consisted of 8 non-obese subjects with normal carbohydrate tolerance (group A), 8 non-obese (group B) and 8 obese (group C) subjects with maturity onset type diabetes mellitus controlled diet alone.

Group B was characterized by a lack of IRI-response to glucose whereas a hyperinsulinaemia was found both in group A and C. The fasting IRG levels increased from controls (29.7 ± 2.3 pmol/1) to group A (36.7 ± 6.5 pmol/l; n.s.), group B 47.3 ± 8.8 pmol/l; P < 0.05) and group C (57.7 ± 8.2 pmol/l; P < 0.01). In group A the IRG concentration pattern was comparable with that of the controls. On the contrary, in groups B and C the IRG levels remained significantly higher inspite of the excessive hyperglycaemia achieved by the glucose infusion, suggesting a reduced suppressibility of the alpha cell function to glucose. In addition, the latter groups were characterized by a lack of an IRG rebound after termination of the glucose infusion. No correlation was found between hyperglycaemia and the degree of IRG rebound in all groups so far studied. A diminished molar IRI-IRG-ratio was found in group B whereas an increase ratio was recorded in groups A and C during glucose infusion. There were no correlation between IRG secretion and relative body weight, carbohydrate tolerance or IRI-response to glucose.

Our findings suggest a normal alpha cell response to glucose in hyperlipoproteinaemia without obesity and carbohydrate intolerance. The abnormal alpha cell function in non-obese and obese hyperlipoproteinaemics with maturity onset type diabetes mellitus is a feature characteristic of diabetes than of hyperlipoproteinaemia.
The effect of weight gain on gonadotrophins and prolactin in anorexia nervosa
Authors: Isaacs A. J. , Leslie R. D. G. , Gomez J. , Bayliss Richard
Published: December 2008

Serum levels of gonadotrophins and prolactin and their response to luteinizing hormone/follicle stimulating hormone - releasing hormone (LRH) and thyrotrophin releasing hormone (TRH) were measured in 14 females with anorexia nervosa when at low body weight and again in 6 cases during, and 12 cases after weight gain. Mean serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were low initially and whereas FSH increased significantly with weight gain, LH levels remained subnormal in most patients. LH responses to LRH were grossly impaired or absent in patients whose weight was below 75% of the ideal, but increased dramatically above this weight overshadowing the more modest increase in FSH response. In three patients, however, impaired LH responses persisted as ideal weight was approached. Basal prolactin levels were well within the normal range in all patients. During weight gain there was no change in basal levels but the prolactin level 20 min after TRH was significantly increased.
Serum myoglobin in thyroid disease
Authors: Karlsson F. A. , Dahlberg P. A. , Venge P. , Roxin L. E.
Published: December 2008

Serum myoglobin levels were measured longitudinally in patients undergoing therapy because of various thyroid disorders. Elevated myoglobin values - 72.6 (58.7–89.7) μg/l (mean ± sem) were found in a group of hypothyroid subjects. The degree of myoglobin increase seemed related to the severity of hypothyroidism. When rendered euthyroid the myoglobin levels of these patients were normalized − 41.0 (37.3–45.1) μg/l. In patients with hyperthyroidism, due to Graves' disease or subacute thyroiditis (de Quervain), only minor changes of myoglobin values within the reference range of healthy subjects, were measured. This suggests that mechanisms not affecting myoglobin release are responsible for the muscular weakness of thyrotoxic patients.
Immunochemical properties of trypsin fragments of human thyroglobulin
Authors: Dominici R. , Salabé G. B. , Diodato A. , Sorcini M. , di Iorio M. G. , Carta S.
Published: December 2008

Purified human thyroglobulin (Tg) was enzymatically digested with trypsin. After completion of digestion, the tryptic digest was fractionated by gel filtration on a Biogel A 1.5 m column. Further separation and isolation of the major peak C was carried out on a Sephadex G-75 column. Nine fractions were separated and antigenic properties evaluated by a specific and sensitive radioimmunoassay using a rabbit antiserum to 19S Tg and three different antisera from patients with autoimmune thyroid diseases. The Tg fragments react with both hetero- and auto-antisera. The highest antigenic activity was found on larger fragments, but a fairly good activity was also observed on fragments (C6, C7) with lower molecular weight.

Antigenic determinants of Tg differ in individual sera suggesting that different sets of determinants elicit the autoimmune process.