bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgery depresses pulsatile growth hormone release in rats for up to 2 days
Authors: Obonsawin M. C. , Shin S. H. , Arrowsmith J.
Published: December 2008

Abstract. In order to study the pulsatile release of rat growth hormone in a stress-free environment, many investigators obtain sequential blood samples from individual rats bearing an indwelling, right atrial cannula. There has been little systematic study of the stressful effects of the cannulation procedure on the pulsatile release of rat growth hormone. We examined the acute and chronic effects of right atrial cannulation on growth hormone release in male rats by monitoring plasma growth hormone concentration at every 2 min. Right atrial cannulation was performed under ether anaesthesia. Blood was collected from the rats for a 2 h period (11.00–13.00 h), either immediately following, or 2, 3 or 7 days following the surgery. When blood was collected 7 days after surgery, growth hormone was released in large bursts. The amplitude of these bursts however, did not differ significantly from the bursts of growth hormone in rats cannulated 3 days prior to blood collection. On the other hand, the bursts of hormone release in rats cannulated immediately or 2 days before blood collection were significantly smaller in amplitude than those in rats cannulated 3 days before collection, but were not significantly different from each other. In many of the rats cannulated immediately before or 2 days before blood collection, pulsatile growth hormone release was completely suppressed. The results of the study suggest that blood sampling from right atrial cannulae to measure the plasma concentration of rat growth hormone should not be carried out until at least 3 days after the cannulation procedure.
Serum thyroglobulin (Tg) stimulation with bovine TSH: a useful test for diagnosis of congenital goitrous hypothyroidism due to defective Tg synthesis
Authors: Medeiros-Neto Geraldo A. , Marcondes José A. , Cavaliere Humberto , Wajchenberg Bernardo L. , Knobel Meyer
Published: December 2008

Abstract. Sixteen patients with congenital goitre were submitted to a bovine TSH stimulation test (bTSH), and serum thyroid hormones (T3, T4), TSH and thyroglobulin (Tg) were measured before and after bTSH injection. In 9 patients with an organification defect basal levels of Tg were normal (19.4 ± 3.1 μg/l) rising after bTSH to a mean level ± sem of 37.3 ± 4.1 μg/l. Six patients with defective Tg synthesis or release had a mean basal level of serum Tg of 8.7 ± 1.9 μg/l (mean ± sem) and failed to raise serum Tg concentrations after bTSH (mean ± sem: 10.4 ± 2.1 μg/l). In both groups a modest although significant (P < 0.05) change in serum thyroid hormones after bTSH was noted. We conclude that the bTSH test may be used to distinguish the group with defective Tg synthesis or release from other types of congenital goitre.
Prenatal diagnosis of a thyroglobulin synthesis defect in goats
Authors: Kok K. , van Dijk J. E. , Fokkens R. H. , Gons M. H. , de Vijlder J. J. M.
Published: December 2008

Abstract. A strain of goats with congenital goitre due to a thyroglobulin (Tg) synthesis defect was studied. All goats excreted low molecular weight iodinated material (LOMWIOM) in their urine, but non-goitrous goats excreted in the LOMWIOM fraction less than 5 μg iodine per 24 h and the goitrous ones more than 15 μg iodine per 24 h.

Prenatal diagnosis of the Tg synthesis defect in goats is possible since non-goitrous goats pregnant with goitrous kids excrete in the LOMWIOM fraction more than 10 μg iodine per 24 h while non-goitrous goats pregnant with non-goitrous kids excrete 10 μg or less iodine per 24 h as LOMWIOM. In 24 out of 25 cases a correct diagnosis could be made in the last 47 days of pregnancy. We argue that prenatal diagnosis of analogous defects in man may also be possible, using the excretion of LOMWIOM in maternal urine as yard-stick.

By means of field desorption mass spectrometry (FOMS) and high performance liquid chromatography (HPLC) monoiodohistidine was identified as the major component of the LOMWIOM fraction in the urine of goitrous goats.
Effects of eledoisin on thyrotrophin secretion in rats
Authors: Mitsuma Terunori , Nogimori Tsuyoshi , Sun De Heng , Chaya Masahiro
Published: December 2008

Abstract. The effect of peripheral administration of eledoisin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. Eledoisin (500 μg/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay.

The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after eledoisin injection, whereas its plasma concentration tended to decrease, but not significantly. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. Plasma thyroid hormone levels did not change significantly. Plasma ir-TRH and TSH responses to cold were inhibited by eledoisin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine-pretreated group, the inhibitory effect of eledoisin on TSH levels was prevented, but not in the l-dopa- or 5-hydroxytryptophan-pretreated group. These drugs alone did not affect plasma TSH levels at the dose used. The inactivation of TRH immunoreactivity by plasma or hypothalamus in vitro after eledoisin injection did not differ from that of controls.

These findings suggest that eledoisin acts on the hypothalamus to inhibit TRH release, and its effects are modified by amines of the central nervous system.
Correlation between urinary oestrogen levels determined by haemagglutination inhibition reaction and serum oestradiol levels determined by radioimmunoassay
Authors: Seki Katsuyoshi , Seki Mitsunori , Kato Koichi
Published: December 2008

Abstract. Measurement of urinary or blood oestrogen is essential for a precise monitoring of follicular development in gonadotrophin therapy. Blood oestradiol levels are considered most accurately to reflect follicular maturation. Although radioimmunoassays (RIA) for oestradiol yielding rapid results are now available, they require qualified technicians and equipment for RIA. Recently, a simple, rapid method for determining urinary total oestrogen has been developed by Mochida Pharmaceutical Co. Ltd., Japan. To determine whether this kit may be applicable to monitoring gonadotrophin therapy, urinary total oestrogen concentrations measured by the kit were compared with serum oestradiol levels determined by RIA in patients who were treated with gonadotrophin. Urinary total oestrogen concentrations in samples obtained either at 07.00 h (first morning urine specimen) or at 09.00 h significantly correlated with serum oestradiol levels. Thus, urinary total oestrogen concentrations determined by the kit appear to reflect follicular development accurately, and are considered applicable to monitoring gonadotrophin therapy. Correction of the urinary total oestrogen concentrations by the creatinine level significantly improved the correlation between urinary total oestrogen values and serum oestradiol levels. Therefore, the primary total oestrogen values should be corrected by the creatinine level.
Circulating immunoreactive somatostatin in man. Effect of age, pregnancy, growth hormone deficiency and achlorhydria
Authors: Webb Susan M. , Wass John A. H. , Penman Erica , Murphy M. , Serrano José , Binimelis Jaume , Pavía Carlos
Published: December 2008

Abstract. Plasma immunoreactive somatostatin (IRS) levels were measured fasting at 09.00 h in groups of adult individuals and children of different ages, as well as in pregnant women, in patients with pernicious anaemia documented to be achlorhydric, and in children with growth hormone deficiency.

There was a gradual rise in the mean level of IRS from the third decade (mean 35.8 ± 3.8 pg/ml), which reached significance at the seventh (61.1 ± 8.4 pg/ml), eighth (66.7 ± 5 pg/ml) and ninth decade (82.6 ± 13.8 pg/ml). No change was observed in the second 28.3 ± 3.8 pg/ml) and third (31.1 ± 3.2 pg/ml) trimester of pregnancy when compared with matched, non-pregnant controls (29.7 ± 2.2 pg/ml); however, the children aged under 2 years (69.6 ± 11.2 pg/ml) had significantly higher values than the eldest group (12 to 16 years old) (46.3 ± 7.2 pg/ml) (P < 0.05). In achlorhydric patients, basal (27.2 ± 3.7 pg/ml; P < 0.01) and postprandial IRS (42.8 ± 7.7 pg/ml; P < 0.001) was significantly lower than in a matched, normal control group (basal 59.4 ± 7.2; postprandial 132.1 ± 26.3 pg/ml). Growth hormone deficiency was not associated with any differences in circulating IRS, basally or after insulin hypoglycaemia, when compared with values in normal children.

These results would suggest, 1) that age has a significant effect on plasma IRS, and should be considered in the interpretation of fasting plasma levels of IRS; 2) that pregnancy and growth hormone deficiency is not accompanied by any changes in circulating IRS and presumably, somatostatin binding proteins; 3) that gastric acid is necessary for a normal release of IRS from the gastrointestinal tract to the circulation.
Heterogeneity of human lutropin. Detection and identification of α- and β-subunits
Authors: van Ginkel L. A. , Loeber J. G.
Published: December 2008

Abstract. A highly purified LH preparation, prepared from human pituitaries (NM14) was studied using immunochemical and in vitro biological techniques. Using isoelectric focusing 5 different biologically active components could be detected, 4 of which were located between pH = 7.0 and 8.6, one was located at pH = 4.9. The biological activity in the acidic part of the pH gradient is probably due to the formation of an artefact during storage in solution. The experiments were performed with special emphasis on the occurrence of LH subunits, for which until now no pI-values have been reported.

Using specific radioimmunochemical (RIA) systems at least 7 different α-subunit components and 4 different β-subunit components could be detected. The presence of even more components is likely. The α-subunit components, with pI-values of: 4.6, 5.2, 6.0, 7.1, 8.1, 8.8 and 9.7, were located spread over the entire pH-gradient whereas all β-subunit components were located above pH = 7.5, the pI-values being 7.7, 8.4, 8.5 and 10.4.

The identification of these components as α- or β-subunit was based on the relative response in the different RIA systems, the absence of biological activity and the response changes during incubation at 37°C.

Refocusing of the above mentioned biologically active components individually resulted each time in a single component with a pI-value identical to its corresponding 'parent'. After incubation at 37°C of these components each time the same variety of subunit components was found with discrete pI-values, identical to those above.
Regulation of gonadotrophin secretion in male mice from birth to adulthood. Response to LRH injection, castration and testosterone replacement therapy
Authors: Jean-Faucher Ch. , Watik N. El , Berger M. , de Turckheim M. , Veyssière G. , Jean Cl.
Published: December 2008

Abstract. Plasma LH and FSH concentrations were determined by radioimmunoassay in male mice from birth to adulthood after LRH injection, castration and testosterone replacement therapy. Except at birth for LH, LRH significantly increased circulating levels of both gonadotrophins at all stages studied. It is suggested that a change in the pituitary LH response to LRH occurs around puberty and perhaps represents the time of initiation of pubertal processes. At all stages studied (except the infantile stage for LH) castration resulted in a significant rise in circulating LH and FSH levels. The magnitude of LH response to castration increased with age but not that of FSH. Testosterone replacement therapy, inducing supra-physiological circulating testosterone levels, was ineffective to depress the post-castration rises of LH and FSH levels.
Effect of haemodialysis on plasma ADH levels, plasma renin activity and plasma aldosterone levels in patients with end-stage renal disease
Authors: Iitake Kazuhiro , Kimura Tokihisa , Matsui Kuniaki , Ota Kozo , Shoji Masaru , Inoue Minoru , Yoshinaga Kaoru
Published: December 2008

Abstract. Changes in plasma ADH levels and plasma aldosterone levels (PA) were studied in patients with end-stage renal disease (N = 40). The patients were divided into two groups according to their plasma renin activity (PRA) into a low renin (LR, n = 9) and a high renin group (HR, n = 31). The metabolic clearance rate (MCR) of plasma ADH was also investigated in 4 patients and 5 normal volunteers. Additionally, it was examined whether plasma ADH, aldosterone and renin were permeable through the dialysis membrane. Pre- and post-dialysis plasma ADH levels in LR were similar to those in the HR group. However, pre- and post-dialysis PA in the HR group were significantly greater than those in the LR group. Post-dialysis PRA was significantly increased in HR compared to pre-dialysis, but not in LR. Pre- and post-dialysis plasma osmolality was increased in both groups, but effective plasma osmolality (EPosm) was within the normal range. There was a significant correlation between EPosm and plasma ADH level both before and after haemodialysis, but the majority of the abnormally high values of ADH compared to the normal values was found within the normal range of EPosm. The patients exhibited high blood pressure and a rise in body weight, and haemodialysis caused a significant fall in body weight and blood pressure in both groups. MCR of ADH was significantly lower in the patients than that in normal subjects. Plasma ADH proved to be permeable through the dialysis membrane in all cases, but aldosterone in only a few cases. Renin was not permeable.
Gonadotrophic regulation of prolactin mediated progesterone secretion in vitro
Authors: Alexander J. Steven , Crisp Thomas M.
Published: December 2008

Abstract. The effects of preincubating rat granulosa cells with FSH, LH, and Prl on subsequent Prl mediated progesterone secretion were investigated. Granulosa cells were isolated from ovarian follicles 50 h after injection of 5 IU PMSG and were then plated on poly-l-lysine coated coverslips in serum supplemented medium. Cells were preincubated for 24 h in the absence of hormones (control) or with the addition of either 0.25, 2.5, 25 ng/ml rat FSH or rat LH, or 1 μg/ml rat Prl. Following the preincubation period, cells were maintained for an additional 6 or 8 days in the presence or absence of 1 μg/ml Prl. When cells were preincubated with FSH or LH, only the two higher concentrations (2.5 and 25 ng/ml) stimulated significantly more progesterone secretion than control cultures during the 24 h preincubation period. For each series of preincubations, cells cultured for 6 or 8 days in the presence of Prl secreted significantly more progesterone at each day of culture than cells cultured without Prl. Cells preincubated and cultured with Prl secreted only 3–7-fold more progesterone than cells preincubated in control medium and then cultured with Prl. Preincubation with FSH or LH promoted a 20–45-fold increase in Prl mediated progesterone secretion compared to control preincubation cultures that also subsequently were cultured with Prl. The magnitude of Prl mediated progesterone secretion observed through 6 days of culturing was dose dependent on the preincubation concentration of FSH or LH. The establishment of an in vitro model system in which gonadotrophins enhance the responsiveness of granulosa cells to Prl in serum supplemented medium provides the opportunity for study of the regulatory mechanisms involved with the induction and maintenance of such responsiveness.
Cushing's syndrome presenting the coexistence of a pituitary corticotrophic cell hyperplasia and a unilateral functional adrenal adenoma
Authors: Watanobe Hajime , Kawagishi Takahiko , Hirai Yuichi , Sato Tatsuro , Tsutsui Masahiro , Kamata Yoshimasa , Takebe Kazuo
Published: December 2008

Abstract. A very unusual case of Cushing's syndrome is presented. Most of the preoperative biochemical and radiological examinations were compatible with Cushing's syndrome owing to a right adrenal adenoma. Exceptional findings include normal concentrations of adrenocorticotrophin (ACTH) in plasma as well as a disturbance of its circadian rhythmicity and a significant adrenocortical responsiveness to exogenous ACTH. Secretory patterns of ACTH did not change even after right adrenalectomy.

Studies in vitro revealed that the adenoma itself, but not the surrounding normal adrenal, was the source of cortisol secreted in response to ACTH. Post mortem examinations disclosed unexpectedly a hormonally inactive left adrenal adenoma and a focal hyperplastic lesion of the anterior pituitary with an ACTH concentration 53 times higher than that of the remaining tissue of the gland.

It is a possibility that this case may have represented a transition between pituitary-dependent adrenocortical hyperplasia and adrenal adenoma to this date reported in only one similar case.
The measurement and characterisation by high pressure liquid chromatography of immunoreactive α-melanocyte stimulating hormone in human plasma
Authors: Thody A. J. , Fisher C. , Kendal-Taylor P. , Jones M. T. , Price J. , Abraham R. R.
Published: December 2008

Abstract. Immunoreactive α-MSH was found in human plasma and in normal subjects ranged from < 10–45 pg/ml. Plasma α-MSH concentrations were within the normal range in 13 out of 15 subjects during the last trimester of normal pregnancy and only just outside the normal range in the remaining two. Elevated plasma α-MSH concentrations were found in 6 of the 11 patients with Nelson's syndrome and in 10 of the 11 patients with pituitary dependent Cushing's disease. Separation on high pressure liquid chromatography (HPLC) revealed two major peaks of immunoreactivity. These peaks, which were identified as des-acetyl α-MSH and α-MSH were similar in size in normal subjects and Cushing's disease. In Nelson's syndrome, on the other hand, there was a greater proportion of des-acetyl α-MSH and it is possible that this peptide is secreted from tumour cells of anterior lobe origin. Although there was no correlation between the circulating α-MSH and the degree of pigmentation the high concentrations of plasma immunoreactive α-MSH in Cushing's disease and the HPLC profiles in Nelson's syndrome could provide useful information as to the localization of the defects in these particular disorders.
Autologous mixed lymphocyte reaction in Graves' disease: relationship to clinical status
Authors: Bagnasco M. , Ciprandi G. , Orlandini A. , Torre G. , Canonica G. W. , Giordano G.
Published: December 2008

Abstract. The autologous mixed lymphocyte reaction (AMLR), i.e. the ability of T lymphocytes to proliferate when cultured with autologous non-T cell fractions, is an 'in vitro' phenomenon showing immunological memory and specificity, probably related to the cooperation ability of immunocompetent cells.

We have evaluated AMLR in 27 patients with Graves' disease of varying clinical status (untreated and treated with antithyroid drugs, surgery or 131I). The results obtained show:

Impaired AMLR in untreated patients (as in other autoimmune diseases).

Significantly higher AMLR in cured patiens, and that

AMLR in cured patients varies with the treatment (higher after surgery or radioiodine than after medical treatment).

These results are consistent with the hypothesis of a functional defect of T cells in Graves' disease, which improves when clinical remission is achieved.
Endocrine control of extrathyroidal peroxidases and iodide metabolism
Authors: De Swapan K. , Ganguly Chayan K. , Chakraborty Tapan K. , Bose Arya K. , Banerjee Ranajit K.
Published: December 2008

Abstract. The role of the thyroid and adrenal glands on iodide transport and peroxidase-catalyzed formation of iodotyrosines in extrathyroidal tissues such as stomach and submaxillary glands has been investigated. Thyroidectomy stimulates iodide concentration and iodotyrosine formation in stomach, sensitive to the administration of thyroxine but having no effect on the peroxidase activity. In contrast, although thyroidectomy stimulates the submaxillary peroxidase which is reversed on treatment with thyroxine, it has no effect on iodide concentration and organification in the submaxillary gland. Gastric peroxidase activity is specifically stimulated by adrenalectomy and is inhibited by glucocorticoids which also inhibit iodotyrosine formation in stomach.
Pulsatile GnRH therapy – an alternative successful therapy for induction of ovulation in infertile normo- and hyperprolactinaemic amenorrhoeic women with pituitary tumours
Authors: Bergh Torbjörn , Skarin Göran , Nillius Sven Johan , Wide Leif
Published: December 2008

Abstract. Pulsatile treatment with gonadotrophin-releasing hormone (GnRH) was given to induce ovulation in 3 infertile, amenorrhoeic women with pituitary tumours not suitable for conventional therapy with human gonadotrophins or dopamine agonists. Two of the women had prolactinomas and the third a non-secreting adenoma. The GnRH therapy resulted in ovulations in all the 3 women, in 2 of them despite marked hyperprolactinaemia. Two women conceived and had term pregnancies. One pregnancy was uneventful while the woman with the non-secreting tumour developed symptoms of raised intracranial pressure. These symptoms rapidly disappeared when bromocriptine therapy was instituted. Chronic pulsatile GnRH administration is an effective alternative treatment for induction of ovulation in some amenorrhoeic women with pituitary tumours.
Effects of oestradiol-17β and LRH upon the two fractions of pituitary follicle-stimulating hormone separated by concanavalin-A chromatography
Authors: Ulloa-Aguirre Alfredo , Torra Emma , Domínguez Roberto , Scherpbier Robert , Larrea Fernando
Published: December 2008

Abstract. The effects of oestradiol-17β (E2) and LRH upon the two fractions of pituitary follicle stimulating hormone (FSH) obtained by concanavalin A (Con A) chromatography were studied. Anterior pituitary glands were removed from adult intact rats at different times throughout the oestrous cycle, and from long-term ovariectomized (Ovx) rats after specific endocrine treatments. The presence, relative ratio and biological activity of each Con A separable FSH fraction were assessed by a specific radioimmunoassay and by an in vitro bioassay. After separation by concanavalin A chromatography, glands from intact rats sacrificed during the days of oestrus, dioestrus 1 and dioestrus 2, exhibited constant relative ratios (U:B FSH ratio) of the two FSH fractions so separated (Con A unbound and bound FSH), whereas donors sacrificed at the morning and early afternoon (13.00– 15.00 h) of the day of pro-oestrus, showed the highest U:B FSH ratio; this ratio abruptly declined at the time of the FSH surge, after 15.00 h of pro-oestrus. Ovx rats exhibited lower ratios than intact animals. Pituitary extracts from Ovx donors under short-term (20 h) E2 exposure (condition which decreased pituitary sensitivity to LRH), showed the lowest U:B FSH ratio, whereas glands from Ovx rats exposed to conditions which caused increased pituitary LRH exposure (immediately before the oestradiol-induced FSH surge or after injection of 100 ng of LRH) showed an increase in their U:B FSH ratio, as compared with Ovx and Ovx + E2 (20 h) rats. Ovx animals exposed to oestradiol (during 33 h), phenobarbitone (at 30 h) and 200 ng of LRH (at 31 h), exhibited a dramatic decrease in the pituitary content of the Con A unbound FSH fraction, similar to that shown in intact rats during the late afternoon of pro-oestrus. Both FSH fractions exhibited similar in vitro biological activity and apparent molecular weight. These studies demonstrate that the existing endocrine milieu regulates the carbohydrate content and/or arrangement of the FSH molecule, and hence, the type of FSH produced by the anterior pituitary gland.
Primary aldosteronism with normal aldosterone levels in blood and urine
Authors: Nomura Kaoru , Han Doo Chol , Jibiki Kazuko , Demura Hiroshi , Tsushima Toshio , Shizume Kazuo
Published: December 2008

Abstract. A 47 year old woman examined for hypertension (200/100 mmHg) was normokalaemic, and had low plasma renin activity (PRA) (0.1 ng/ml · h) and normal aldosterone levels in both plasma (7–13 ng/dl) and urine (4.7–7.4 μg/day). Computed tomography (CT) and scintiscan indicated an adenoma on the right adrenal gland, which was then removed. The histology of the adenoma and analysis of the aldosterone content were compatible with the criteria for an aldosterone-producing adenoma. Three months after surgery, her hypertension had improved, serum potassium levels had increased slightly, and PRA had normalized. This was an unusual form of primary aldosteronism which showed normal levels of aldosterone in both blood and urine.
Effect of etomidate on cortisol biosynthesis: site of action after induction of anaesthesia
Authors: De Coster R. , Helmers J. H.J. H. , Noorduin H.
Published: December 2008

Abstract. To determine the site of inhibition of etomidate on cortisol biosynthesis, plasma cortisol, aldosterone, 17α-hydroxyprogesterone, 11-deoxycortisol and ACTH levels were measured in healthy women before and after the administration of a single dose of either 0.20 mg kg−1 etomidate (mean value, n = 10) or 3.15 mg kg−1 thiopental (n = 9) for induction of anaesthesia in a randomized trial.

Etomidate produced a smaller increase in plasma cortisol and had a later onset of action than thiopental. Plasma ACTH levels, however, rose higher in the etomidate-induced patients to reach peak levels 6 h after drug administration. In the same group, plasma aldosterone remained below the control levels but still within the normal range, whereas it rose about 2-fold in the thiopental group. Plasma levels of 17α-hydroxyprogesterone and 11β-deoxycortisol were hardly modified after thiopental but increased significantly and remained high for 6 h after etomidate injection. This marked rise in precursors together with a blunted and delayed cortisol response to high ACTH levels, and slightly lowered plasma aldosterone concentration indicates a blockage of 1 1β-hydroxylation in adrenal cortisol synthesis after induction of anaesthesia with etomidate.
Incomplete androgen insensitivity: asymmetry in morphology and steroid profile and metabolism of the gonads. An analysis of a case
Authors: Fredricsson Bengt , Carlström Kjell , Kjessler Berndt , Lindstedt Jan , Plöen Leif , Ritzén Martin , de la Torre Bartolomé
Published: December 2008

Abstract. A patient with clinical manifestations of the incomplete androgen insensitivity syndrome was studied with respect to peripheral blood levels of steroids and steroid sulphates before, during and after gonadectomy. Steroid and steroid sulphate concentrations were also analyzed in spermatic venous blood and gonadal tissue collected during surgery. The metabolic capacity of gonadal tissue was also studied in vitro using progesterone, dehydroepiandrosterone sulphate and oestrone sulphate as substrates.

Profound differences between the two gonads were noted with respect to both steroid content and release into pampiniform veins and to in vitro conversion of progesterone and oestrone sulphate. Histological examination revealed the presence of seminiferous tubules with carcinoma in situ in both gonads.

It is suggested that the differences between the gonads may be due to an autonomous steroid production in the right gonad in spite of adequate or even elevated gonadotrophic stimulation resulting in a steroidogenic situation resembling the complete androgen insenstitivity syndrome, while the conditions found in the left gonad more resembles the incomplete form of the disease.
Bioassayable growth hormone activity in blood from healthy individuals and acromegalic patients
Authors: Thorngren Karl-Göran , Hallengren Bengt
Published: December 2008

Abstract. Biological growth activity (bioassayable GH) was determined in blood from healthy individuals and from patients with acromegaly using the rate of longitudinal bone growth in hypophysectomized rats with tetracycline as intravital marker. Also radioimmunoassayable GH and somatomedin A activity were determined.

In pooled plasma or serum from normal subjects no bioassayable growth activity was demonstrated. In the clinically active acromegalic patients as a group as well as in one individual patient there was a significant (P <0.05) bioassayable growth activity in serum as compared to serum from normal subjects. The bioassay determination of GH in plasma/serum from normal subjects and acromegalic patients was hampered by the toxicity and the problems connected with the administration of large volumes.
Plasma thyrotrophin (TSH) response to intrahypothalamic injection of an α2-adrenergic receptor agonist (clonidine)
Authors: Ishikawa Koichi , Kakegawa Tadao , Suzuki Mitsuo
Published: December 2008

Abstract. To delineate the site at which the central noradrenergic (NE) system may exert its stimulatory influence on the thyrotrophin (TSH) secretion, plasma TSH concentrations were measured before and after clonidine (an α2-agonist) administration to the hypothalamus of unanaesthetized, unrestrained rats. When the animals received a simultaneous injection of clonidine (0.2 μg) and phenoxybenzamine (2.0 μg) into the dorsomedial nucleus (DMN)/the paraventricular nucleus (PVN). a significant rise in TSH levels was observed. Injection of the mixture into the anterior hypothalamus, posterior hypothalamus, ventromedial hypothalamus, and arcuate nucleus had no influence on the plasma TSH concentration. Clonidine (10.0 μg/100 g body weight) and phenoxybenzamine (100 μg/100 g body weight) injected into the jugular vein also caused a prompt increase in the plasma TSH concentration. In rats with an intact small hypothalamic island, the TSH response to the iv injection of the drugs was considerably diminished. These data support the view that NE receptors in the DMN/PVN are of importance in exerting an NE-stimulatory influence on the TSH secretion, probably through the TRH neurons.
Beneficial effects of intensive plasma exchange followed by immunosuppressive therapy in severe Graves' ophthalmopathy
Authors: Glinoer D. , Etienne-Decerf J. , Schrooyen M. , Sand G. , Hoyoux P. , Mahieu P. , Winand R.
Published: December 2008

Abstract. Nine patients with severe Graves' ophthalmopathy were treated by intensive plasma exchange, followed by immunosuppression. Severity of ocular involvement and response to therapy were evaluated clinically by numerical scoring (ophthalmopathy index). Serum thyroid stimulating immunoglobulins (TSI) and urinary excretion of glycosaminoglycans (GAG) were measured immediately before and immediately after plasmapheresis.

Plasma exchange was rapidly accompanied by marked clinical improvement in 8/9 patients. The most marked effects were on soft tissue involvement, proptosis, intraocular pressure, and visual acuity. The ophthalmopathy index decreased from 9.7 ± 4.1 to 5.7 ± 2.2 (P <0.001) after plasmapheresis. Serum TSI levels were initially elevated in 6 patients and remained positive in 3 patients after treatment. Urinary GAG excretion was initially 2- to 12-fold normal levels and was decreased by 60%. After plasmapheresis, patients received immunosuppressive drugs for 3–6 months. The follow-up period, after withdrawal of drugs, ranged from 5 to 38 months with a median of 17 months. The ocular condition remained stable in 6 patients. Three patients had a relapse 1 year after plasmapheresis: they were treated a second time by plasma exchange with subsequent improvement.

In conclusion, intensive plasma exchange provided prompt and effective improvement in patients with severe progressive Graves' ophthalmopathy. This therapeutic procedure, followed by immunosuppression, gave long lasting results. Relapses were responsive to plasmapheresis therapy. The data suggest that plasma exchange may represent the best primary treatment for severe progressive Graves' ophthalmopathy
Loss of adrenergic regulation of cAMP production in the FRTL-5 cell line
Authors: Brandi Maria Luisa , Rotella Carlo M. , Zonefrati Roberto , Toccafondi Roberto , Aloj Salvatore M.
Published: December 2008

Abstract. Rat thyroid cells in primary culture augment cAMP production when challenged with β-adrenergic agonists; at 10−5m the potency is isoproterenol > nor-epinephrine > epinephrine. In analogy with human thyroid cells, rat thyroid primary cultures display α-adrenergic-stimulated cGMP production which inhibits TSH and norepinephrine stimulation of cAMP. Adrenergic regulation of cyclic nucelotide production is lost in the cloned thyroid cell line of rat origin known as FRTL-5. Also the potentiating effect of phentolamine on TSH stimulation of cAMP production in thyroid primary cultures becomes an inhibitory one in the FRTL-5 cells. Neither 'soluble factors' nor contamination of other cell populations could account for the different behaviour of the primary culture and the cell line toward adrenergic regulation. The reported activation by norepinephrine of iodide efflux in FRTL-5 cells rules out the loss of specific adrenergic receptors in the FRTL-5 cells. It is proposed that the cloning of FRTL-5 cells from primary cultures causes an 'alteration' in the coupling of adrenergic receptors to the adenylate cyclase system. This alteration does not affect those mechansism of message transduction that do not involve cAMP as the signal.
Selective determination of C-terminal (70–84) hPTH: elevated concentrations in cholestatic liver disease
Authors: Rittinghaus E. F. , Jüppner H. , Burdelski M. , Hesch R. D.
Published: December 2008

Abstract. In order to obtain a better resolution of circulating PTH-fragments, we developed a radioimmunoassay with an antiserum raised against the synthetic 70–84 hPTH molecule in a sheep. [125I](69 Tyr) 70–84 hPTH was used as the radioactive tracer with the antiserum at a final dilution of 1:200 000. Displacement curves showed that only the 70–84 hPTH, (69 Tyr) 70–84 hPTH and 53–84 hPTH fragments were able to compete with the tracer. Synthetic 28–48 hPTH, 44–68 hPTH, (61 Tyr) 62–68 hPTH, purified 1–84 hPTH and 53–84 bPTH showed no ability to displace the tracer indicating that the idiotype of the antibody is directed against the 70–84 portion that is usually hidden within the globular structure of the intact molecule. Healthy adults revealed PTH-peptide levels of 153 ± 86 pg/ml (mean ± 2 sd); 2 sd range: 67–239 pg/ml.

C-terminal PTH-peptide (70–84 hPTH) concentration was normal in patients with primary hyperparathyroidism and chronic renal failure, thus excluding that neither the kidney nor the parathyroid gland is involved in the generation of this C-terminal PTH-peptide sequence. Increased levels of 70–84 hPTH immunoreactivity were found in most individuals with severe cholestatic liver disease. Since the liver appears to be responsible for part of the peripheral PTH metabolism, this assay system might be used as an indicator of altered liver function.
α- and β-adrenergic receptor activity in circulating blood cells of patients with phaeochromocytoma: effects of adrenalectomy
Authors: Ratge Dieter , Wisser Hermann
Published: December 2008

Abstract. In many tissues adrenergic responsiveness may be impaired by chronic exposure to adrenergic agonists. We examined the effects of high levels of circulating norepinephrine and epinephrine to α2- and β2-adrenoceptors on platelets and mononuclear leucocytes (MNL) of patients with phaeochromocytoma. When compared with controls the density of β2-receptors prior to removal of the tumour was diminished by 67% (500 ± 160 sites/cell, n = 7 vs 1500 ± 350 sites/cell, n = 29; P < 0.001). Binding affinities for [3H]dihydroalprenolol (apparent KD = 0.45 ± 0.16 nmol/l in phaeochromocvtoma, 0.52 ± 0.19 nmol/l in controls) were not significantly different in MNL preparations from the two groups. MNL adenylate cyclase activities in response to 10 μmol/l (-) isoproterenol was lower in the patients (7.5 vs 22 pmol cAMP/106 MNL/10 min; P < 0.001). Conversely, the number of α2-adrenoceptors on platelets and the affinity of these receptors for [3H]yohimbine did not differ between patients and controls.

Ensuing adrenalectomy the regeneration of the β-adrenergic cAMP-system results from a two-phase process. A prompt but moderate restoration was followed by a gradual rise to the normal range within about 1 to 2 months indicating the dynamic character of the β2-adrenoceptor cAMP-system in MNL. We conclude that the downregulation observed in MNL, which appears not to be operative in human platelets, represents only one mechanism of feedback control in the sympatho-adrenal-system protecting tissues from prolonged stimulation by excessive catecholamines.
Incidentally discovered ACTH-dependent adrenal adenoma presenting as 'Pre-Cushing's syndrome'
Authors: Bogner U. , Eggens U. , Hensen J. , Oelkers W.
Published: December 2008

Abstract. An adrenal tumour was incidentally discovered with no clinical signs of Cushing's syndrome. The endocrine evaluation revealed the unique hormonal constellation of an increased urinary cortisol excretion rate, unequivocal suppressibility of plasma and urinary cortisol by dexamethasone, but only to a residual level in the low normal range which probably reflected ACTH-independent 'autonomous' cortisol secretion. After removal of the adrenal mass, urinary cortisol secretion and dexamethasone suppressibility were normalized. In vitro, the tumour cells were as sensitive towards ACTH as 'normal' human adrenal cells, but showed a reduced cortisol production rate per cell. We suppose that the adrenal mass participated in the diurnal rhythm of ACTH-mediated cortisol secretion in vivo, which resulted in an increased cortisol secretion. During the night, when ACTH levels were low, the cortisol production decreased and the hormone levels were probably too low to suppress ACTH. We regard the hormonal findings in our patients as 'Pre-Cushing's syndrome', although the absence of clinical features of Cushing's syndrome remains unclear. We suggest that every patient with an incidentally discovered adrenal mass should have an endocrinological evaluation because the results may help to decide whether or not the adrenal tumour should be removed.
ERRATUM
Authors: del Pozo E. , Neufeld M. , Schlüter K. , Tortosa F. , Clarenbach P. , Bieder E. , Wendel L. , Nüesch E. , Marbach P. , Cramer H. , Kerp L.
Published: December 2008

Abstract. The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201–995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 μg. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 μg of SMS 201–995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P < 0.001 and P < 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P < 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P < 0.001) inhibited by previous sc injection of 50 μg of SMS 201-995. Pretreatment with 50 and 100 μg of SMS 201-995 sc (n = 9) inhibited (P < 0.001) the stimulatory effect of TRH (200 μg iv) on TSH without modifying basal levels. The injection of 100 μg/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials.

Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation.

With its high potency, slow plasma clearance, and long action SMS 201–995 may represent a valuable tool in the long-term management of states of inappropriate GH secretion.
Effect of mouse epidermal growth factor on DNA and protein synthesis, progesterone and inhibin production by bovine granulosa cells in culture
Authors: Franchimont P. , Hazee-Hagelstein M. T. , Charlet-Renard Ch. , Jaspar J. M.
Published: December 2008

Abstract. The effect of mouse epidermal growth factor (EGF) was investigated on DNA and protein synthesis, progesterone and inhibin production by bovine antral granulosa cells. When incubated for the whole period of culture, EGF inhibited inhibin production the second day of culture, progesterone the third and the fourth days whereas it stimulated DNA and protein synthesis only the fourth day of culture. Inhibition of progesterone and stimulation of DNA and protein were dose-dependent when treatment with EGF (pre-incubation) is followed by 24 h without EGF, a stimulatory effect on DNA and protein synthesis was observed after 48 and 72-h preincubation. Progesterone was reduced after 3 day preincubation and inhibin only after 2-day pre-incubation. Effects observed after 3-day pre-incubation were dosedependent. These experiments demonstrated the stimulatory effect of EGF on growth of granulosa cells and its inhibitory action on hormonal production by these cells in vitro.

The inhibitory effect on progesterone and inhibin production is more precocious than stimulatory effect on DNA and protein synthesis. The inhibitory action of EGF on granulosa cell production of progesterone and inhibin could thus be not directly dependent on its stimulatory action on DNA synthesis.
Testicular gonadotrophins and their receptors in human cryptorchidism as revealed by immunohistochemistry and radioreceptor assay
Authors: Hovatta Outi , Huhtaniemi I. , Wahlström T.
Published: December 2008

Abstract. The localisation of endogenous FSH and LH was studied in 4 inguinal adult human testes by the immunoperoxidase technique utilising antisera against the β-subunits of human FSH and LH. The content of available FSH and LH receptors was determined by radioreceptor assay. The Sertoli cells and about 10% of cells in the intersitium the Leydig cells, possibly the testicular macrophages, were similarly FSH-positive in cryptorchidism and control testes. The FSH receptor levels per testis were significantly lower in cryptorchidism than in control testes. Also the localisation of LH in Leydig cells in cryptorchidism was similar to the control testes, but the LH receptor level was significantly lower. These data bring further evidence for Leydig and Sertoli cell malfunction in the inguinal human testis.
Antler cycle and thermolabile and thermostable alkaline phosphatase in white-tailed deer; circannual and circadian rhythms and variation after thyroxine, dexamethasone and ACTH administration
Authors: Sempéré A. J. , Bubenik G. A. , Smith J. H.
Published: December 2008

Abstract. The plasma levels of thermolabile (TLAP) and thermostable (TSAP) alkaline phosphatase were investigated in adult male white-tailed deer. Distinct seasonal variation of TLAP (with highly elevated levels in July) were observed, whereas TSAP exhibits low concentration with a small increase in October. No circadian rhythm was found for TLAP or TSAP. A close correlation (r = 0.98) between TLAP activity and antler weight was found. Administration of ACTH or dexamethasone were ineffective in influencing AP activity. On the other hand, variations of triiodothyronine (T3) levels in plasma induced by thyroxine (T4) injections correlated well with concentration of TLAP.
Effect of an opiate antagonist on the responses of circulating catecholamines and the renin-aldosterone system to acute sympathetic stimulation by hand-grip in man
Authors: Lam K. S. L. , Grossman A. , Bouloux P. , Drury P. L. , Besser G. M.
Published: December 2008

Abstract. The effect of naloxone on the neurohumoral responses to acute sympathetic stimulation by sustained hand-grip in normal man was investigated. Six normal males were studied fasting at 08.30 h, on two occasions at 7-day intervals, with each subject sustaining 30% of his maximal hand-grip on a hand dynamometer for 5 min. Naloxone (8 mg bolus) in 20 ml normal saline, or saline alone, was given 5 min before hand-grip in a randomised double-blind cross-over trial. Blood was sampled for plasma renin activity, serum aldosterone and plasma catecholamines. The study was repeated in the absence of hand-grip. Sustained hand-grip produced significant elevations in mean blood-pressure, circulating adrenaline, noradrenaline and aldosterone. Naloxone, which had no effect on basal catecholamines, plasma renin activity or aldosterone, significantly enhanced the responses in plasma adrenaline, plasma renin activity and serum aldosterone to hand-grip. The increments in blood pressure and noradrenaline were not affected. These results suggest that endogenous opioids modulate the response of the sympathoadrenal and renin-aldosterone systems to acute sympathetic stimulation by a mild stress in man.
Plasma somatostatin is elevated in primary hypothyroidism compared with hyperthyroidism
Authors: Skare Ståle , Hanssen Kristian F. , Norman Nils
Published: December 2008

Abstract. Increased pancreatic somatostatin (somatotrophin release inhibiting factor (SRIF)) has been found in hypothyroid rats. Therefore, we wanted to investigate plasma SRIF in patients with hypo- and hyperthyroidism.

Two groups of patients, 7 cases with autoimmune hypothyroidism, 31–75 years old, and 7 cases with Graves' disease, 19–43 years old, were compared with regard to plasma SRIF before, during and after an arginine infusion (0.5 g/kg/20 min). None of the patients suffered from diabetes mellitus or obesity.

Plasma SRIF was higher in the hypothyroid patients (mean basal value 21.5 ± 3.9, peak value 28.7 ± 5.1 pmol/l) compared with the hyperthyroid group (mean basal value 11.6 ± 3.3, peak value 16.2 ± 4.0 pmol/l). The hypothyroid group also had significantly higher serum insulin values during arginine stimulation. No difference was found in plasma glucagon, serum growth hormone (GH) or blood glucose.

In conclusion, plasma SRIF is elevated in primary hypothyroidism compared with hyperthyroidism. The reason for this finding is uncertain, but a reduced SRIF clearance is a possible explanation. The association of our findings with the reduced glucose tolerance in hyperthyroidism is discussed.
Studies on shrew (Suncus murinus) epidermal growth factor
Authors: Yip T. T. , Tam Y. Y. , Keung W. M. , Xin J. X. , Kong Y. C.
Published: December 2008

Abstract. The shrew SMG contains a very high level of EGF. By heterologous radioreceptor assay, the EGF content was determined to be about 300 pmol/mg wet weight in the male. The content is sex dependent; in the female gland, it is only 4% of the male gland level. EGF level and EGF receptor content in other tissues showed a reciprocal distribution pattern with the parotid gland containing the second highest level of EGF and the liver containing the largest amount of EGF receptor. Shrew EGF is heat stable. It could induce early eyelid opening and incisor eruption in neonatal rat pups at a very low dose level. There is apparently no high molecular weight form of EGF in shrew tissues and body fluids. However, gel chromatography revealed that the foetus contained multiple forms of EGF. The contribution of a high EGF level to the active life in adult shrews and the exceptionally high growth rate in shrew pups are discussed.