bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative correlation between peripheral plasma somatostatin levels and GH responses to GH-RH stimulation tests in children
Authors: Liapi C. , Brion D. Evain , Argente J. , Vaudry H. , Donnadieu M.
Published: December 2008

Abstract. On forty-six fasting and resting children, aged 5–17 years, with short stature (below −2 sd) a growth hormone releasing hormone (GH-RH) stimulation test (2 μg/kg iv bolus, Sanofi) was performed. Twenty-two children were prepubertal, of which, 13 had a constitutional short stature (CSS), nine an idiopathic growth hormone deficiency (IGHD). Twenty-four subjects were pubertal, at the stage II or III of Tanner. Among them, six had a constitutional short stature (CSS) and 18 an idiopathic delayed puberty (IDP). Blood samples were taken for determination of plasma somatostatin-like immunoreactivity (SLI) in chilled test tubes containing EDTA + aprotinin. Plasma SLI levels were measured after extraction and concentration on C 18 Sep Pack columns by radioimmunoassay using an antibody against 1–14 somatostatin. The sensitivity of this assay is around 3 pg/ml. After GH-RH stimulation the peak of GH (mean ± sem) was in prepubertal subjects: 25.3 ± 9.1 μg/l in CSS, and 18.6 ± 10.3 μg/l in IGHD. In pubertal subjects GH peaks were 17.6 ± 8.4 μg/l in CSS and 15.6 ± 3.8 μg/l in children with IDP. No significant differences was found between basal plasma SLI levels in the four groups of subjects, being respectively (mean ± sem) 11.9 ± 1.8 pg/ml in prepubertal subjects with CSS, 9.6 ± 2.6 pg/ml in IGHD, 7.6 ± 1.7 pg/ml in pubertal children with CSS and 6.6 ± 1.5 pg/ml in children with IDP. However, in the 46 children, a significant (r = −0.524, P < 0.001) negative correlation was found between the amplitude of the peak of serum GH after GH-RH injection, and the basal values of SLI. The results suggest a possible regulatory mechanism for circulating somatostatin on GH release after injection of GH-RH.
Transsphenoidal microsurgery for Cushing's disease
Authors: Tagliaferri Mariantonella , Berselli Maria Elisa , Loli Paola
Published: December 2008

Abstract. The study shows the results of transsphenoidal microsurgery in 23 patients with Cushing's disease (CD). Out of the 21 patients with tumour confined to the sella, 18 who had selective adenomectomy, and 1 who underwent total hypophysectomy had correction of hypercortisolism. None of the patients with extrasellar extension of the tumour was cured. In 2 cases no adenoma was found intra-operatively. Post-operative hypoadrenalism was documented in all the patients who remitted clinically. By 3–26 months after surgery, adequate cortisol secretion was found in 12 patients, nine of whom regained diurnal variation of cortisol secretion and ten cortisol responsiveness to hypoglycaemia; a normal or near normal response of cortisol to CRF was documented in 11 out of 17 patients tested. Thyroid and gonadal function was restored in all but two patients in clinical remission, whereas GH responsiveness to hypoglycaemia appeared impaired in 11. Two patients had recurrence of the disease 2 and 3 years, respectively, after successful adenomectomy. In our experience transsphenoidal selective adenomectomy is an effective treatment for most patients with CD; additional therapeutic approaches should be considered for patients bearing pituitary tumours with extrasellar extension, whose surgical outcome is often disappointing.
Variation in serum levels of T3, T4, FT4 and TSH during thyroxine replacement therapy
Authors: Wennlund Anders
Published: December 2008

Abstract. Serum levels of T3, T4, FT4 and TSH were determined in 9 euthyroid patients during 6 h after intake of morning thyroxine replacement medication. Four hypothyroid patients were studied in the same way after the intake of 50 μg thyroxine. In the euthyroid patients the FT4 level increased by 31%, while the increase of T4 was 16% and the increase of T3 11%. In the hypothyroid patients levels of T3, T4 and FT4 did not change after ingestion of 50 μg thyroxine, while the TSH level was decreased by 30%. It is concluded that during thyroxine replacement therapy hormone analysis must be interpreted in relation to the time of thyroxine administration.
The effect of 1-thyroxine treatment on skin accumulation of acid glycosaminoglycans in primary myxoedema
Authors: Lund P. , Hørslev-Petersen K. , Helin P. , Parving H.-H.
Published: December 2008

Abstract. We assessed skin accumulation of acid glycosaminoglycans in ten patients with primary myxoedema (median age 70 years) before and during 1-thyroxine treatment (median 7 months). Eight subjects matched for sex and age served as controls. Acid glycosaminoglycans were determined biochemically on small skin biopsies. Hyaluronic acid was elevated in untreated myxoedema, median 0.60, range 0.39–0.90 μg hexosamine/mg dried defatted tissue compared to a median control value of 0.52, range 0.43–0.65 μg hexosamine/mg dried defatted tissue, P < 0.02. Chondroitin-4,6-sulphate and dermatan sulphate showed no elevation, while heparan sulphate was actually reduced in myxoedema, P < 0.01. 1-thyroxine treatment induced a significant reduction in hyaluronic acid, median 0.41, range 0.24–0.71 μg hexosamine/mg dried defatted tissue, while no consistent changes occurred in the remaining three acid glycosamine glycans. The accumulation of hyaluronic acid might contribute to the peculiar non-pitting oedema of the skin in myxoedema, due to the strong water-binding capacity of the substance.
Secretion of adrenocorticotropin, β -endorphin and calcitonin by cultured medullary thyroid carcinoma cells. Effects of synthetic corticotropin-releasing factor and lysine vasopressin
Authors: Oosterom R. , Verleun T. , Bruining H. A. , Hackeng W. H. L. , Lamberts S. W. J.
Published: December 2008

Abstract. The present study was performed to investigate the potential of human medullary thyroid carcinoma (MTC) cells to secrete ACTH, β-LPH/β-EP. In addition, these studies might shed further light on the possible synthesis of a common precursor molecule for calcitonin (CT), ACTH and β-LPH/β-EP. MTC tissue was obtained from 10 patients (6 familial, 4 sporadic) without clinical and biochemical signs of Cushing's syndrome. Single cell suspensions were cultured for 1 to 2 weeks. Mean basal release of β-LPH/β-EP was 0.76 ± 0.29 (se) ng/106 cells/4 h (n = 10). Dibutyryl cyclic AMP (3 mm) stimulated β-EP release significantly in 3 out of 7 cultures, while Ca2+ (2 mm) had no effect at all. The effects of the physiological regulators of pituitary ACTH and β-LPH/β-EP secretion, synthetic corticotropin-releasing factor (CRF-41) and vasopressin (LVP) were also studied in these MTC cell cultures. LVP (100 nm) had no effect on β-EP release from MTC cells of all 8 cultures investigated. CRF-41 (10 nm) stimulated β-EP release from 5 cultures and was without effect on 4. Maximal stimulation was noticed with 10 nm, while the effect of 100 nm CRF-41 was lower or absent. Stimulation was most outspoken in 3 cultures of familial MTC, whereas in 2 cultures of sporadic MTC CRF-41 stimulated β-EP release marginally only after a 24 h incubation. LVP and/or CRF-41 stimulated CT release significantly in 3 cultures from sporadic MTC, while in these cultures the effect of CRF-41 on β-EP release was either very small or absent. LVP and CRF-41 did not stimulate CT release in 5 and 6 other cultures, respectively. In conclusion, no evidence was obtained for a concomitant secretion of β-EP and CT by MTC cells in culture. Synthetic ovine CRF-41, but not LVP is able to stimulate ACTH and β-EP release especially in cultures from patients with familial MTC, and CRF-41 and LVP stimulate CT release in cultures from some patients with sporadic MTC.
Intestinal phosphate and calcium absorption: joint regulation by thyroid hormones and 1,25-dihydroxyvitamin D3
Authors: Cross Heide S. , Pölzleitner Doris , Peterlik Meinrad
Published: December 2008

Abstract. Thyroxine (T4) and triiodothyronine (T3) activate Na+-dependent inorganic phosphate (Pi) transport in organ-cultured embryonic chick small intestine. Induction of transport activity requires intact protein synthesis and can be expressed in enterocytes with varying degrees of differentiation. T3 and T4 exert their effect independent of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is shown to stimulate Pi uptake only in the final stage of embryonic differentiation. At this time point, a potentiating effect of 1,25(OH)2D3 and T4 on Pi transport in cultured jejunum can be demonstrated. Thyroid hormones appear to stimulate Na+ gradient-driven Pi transport without concomitantly raising (Na+-K+)-ATPase activity. T4 has no influence whatsoever on calcium uptake by cultured embryonic small intestine while 1,25(OH)2D3 is effective at all stages of embryonic development investigated (day 15–20). However, when both hormones were present in the culture medium, the effect of 1,25(OH)2D3 on calcium transport is doubled. Our results suggest that the hyperphosphataemia associated with hyperthyroidism is likely to result, at least in part, from the independent effect of thyroid hormones as well as from their potentiation of the 1,25(OH)2D3 action on Na+-dependent intestinal Pi transport. In addition, their permissive effect on 1,25(OH)2D3-induced calcium absorption provides an explanation for unaltered calcium absorption in a number of hyperthyroid patients, although reduced plasma levels of 1,25(OH)2D3 are generally observed in this condition.
Free and conjugated plasma catecholamines in pheochromocytoma patients with and without sustained hypertension
Authors: Puyó Ana M. , Levin Gloria M. , Armando Inés , Barontini Marta B.
Published: December 2008

Abstract. Ten pheochromocytoma patients, five with paroxysmal hypertension (Group 1), five with sustained hypertension (Group 2) and 15 normals were studied to determine the relationship between differential secretion of the catecholamines (CA) or differences in their sulphoconjugation and the hypertension patterns in these patients. Group 1 patients were studied in the normotensive period. A consistent finding in this study is that permanent hypertensive patients showed the highest free and conjugated norepinephrine (NE) levels while paroxysmal patients studied during the normotensive period showed the highest conjugated epinephrine (E) levels. Although no significant difference was found in levels of free plasma epinephrine in the Group 1 patients, in the ratio of total plasma E/NE, E was clearly predominant. No significant differences could be found in the degree of the per cent conjugation of individual catecholamines between both groups of patients. Group 1 showed a higher (P < 0.05) E and a lower dopamine (DA) per cent conjugation than controls. In conclusion, although the dominant type of CA secreted seems to be the main factor in determining the hypertension pattern, sulphoconjugation ability may also play an important role.
The value of scintigraphy and computed tomography for the differential diagnosis of primary hyperaldosteronism
Authors: Hietakorpi Seppo , Korhonen Timo , Aro Antti , Lampainen Erkki , Alhava Esko , Karjalainen Paavo , Wiljasalo Sirkka
Published: December 2008

Abstract. Adrenocortical adenoma is the most common cause of primary hyperaldosteronism. Most tumours are small, less than 2 cm in diameter and, therefore, their localization may be difficult. We have compared two different methods, adrenal scintigraphy (AS) and computed tomography (CT) in the differential diagnosis of 12 patients with primary hyperaldosteronism. AS was performed using either [131I]cholesterol or 6-iodomethyl-19-norcholesterol during dexamethasone suppression. Of the patients, five showed a normal CT and symmetrical uptake of the isotope as AS. They were considered representative of bilateral hyperplasia. All showed good therapeutic response to spironolactone. Seven patients had an adrenocortical adenoma verified at operation. The CT finding indicated a tumour in five patients. This was correct in four, but in one patient the adenoma was found in the contralateral adrenal gland. In two patients with an adenoma, CT was considered normal. AS correctly indicated the tumour in all seven patients. The uptake was unilateral in six, and bilateral but clearly asymmetrical in one patient. The results indicate that AS is superior to CT in the pre-operative localization of aldosteroma. Although CT remains the primary method for the investigation of these patients, AS should be applied always when CT does not unequivocally indicate the presence and localization of an adrenal tumour.
Plasma arginine-8-vasopressin responses to osmotic or histamine stimulation contribute to the differential diagnosis of central diabetes insipidus
Authors: Laczi F. , Iványi T. , Julesz J. , Janáky T. , László F. A.
Published: December 2008

Abstract. The arginine-8-vasopressin (AVP) responses to osmotic and histamine stimuli were evaluated in 21 patients with central diabetes insipidus (CDI) and compared to those of 10 healthy controls. Plasma AVP was measured by radioimmunoassay. Following the infusion of 2.5% saline, the AVP responses of CDI patients fell into two distinct groups: CDI I gave no response at all, while CDI II responded subnormally. Histamine increased the plasma AVP level significantly in healthy volunteers. Patients with CDI II gave subnormal AVP responses to histamine. The AVP reactions of the patients with CDI I fell into two subgroups: CDI I/A had undetectable plasma AVP, while histamine evoked AVP release in CDI I/B. Histamine trial did not lead to any change in plasma osmolality. The authors conclude that patients with CDI II suffer from a partial CDI, while those with CDI I/A represent a complete form of the disease. The remainder (CDI I/B) presumably have an osmoreceptor failure. Osmotic and non-osmotic stimulation may provide a useful tool in the differential diagnosis of CDI.
Autoimmune-resistance in Graves' disease tissues indication of a structural and functional heterogenicity
Authors: Müller-Gärtner Hans-Wilhelm , Schneider Claus , Schröder Sören
Published: December 2008

Abstract. Out of 256 patients with Graves' disease and a characteristically low echogenic ultrasound appearance of the thyroid gland, 12 patients (4.7%) showed additionally one single or several intrathyroidal focal alterations with high echogenicity. Their volume was 0.2 to 7.0 cm (x̄ ± sd: 1.75 ± 2.24 cm). A common characteristic of the 12 patients was a longstanding history of Graves' disease and antithyroid treatment with thiamazol or carbimazol and a mean age of 55 ± 9 (sd) years (range 42–75 years). The foci with high echogenicity had a normal or macrofollicular histological structure (mean follicle lumen diameter 119.7 μm, as proven by histology in 4 cases) which was significantly higher than follicle lumina of the surrounding Graves' disease tissue (mean follicular lumen diameter 38.3 μm; P < 0.001). The height of follicle epithelium and the nuclei cross-section area of such foci was similar to corresponding normal tissue parameter in 5 out of 7 foci. The 99mTc-uptake of the foci amounted to 40 to 80% in comparison with Graves' disease tissue. 131-iodine autoradiography, thyroglobulin immunochemistry and 125-iodine-TSH binding analysis performed in selected cases confirmed the heterogenicity of these foci.

The data provided evidence that the foci were unresponsive to TSH-receptor mediated stimulation through Graves' immunoglobulins. It is concluded that longstanding Graves' disease can be associated with tissue foci which are in a functional sense resistant to immunogenic stimulation by TSH-receptor autoantibodies.
The polymorphism linked to the human insulin gene: its lack of association with either IDDM or NIDDM in Japanese
Authors: Takeda Jun , Seino Yutaka , Fukumoto Hirofumi , Koh Gyohan , Otsuka Akio , Ikeda Masaki , Kuno Shotaro , Yawata Mikio , Moridera Kunisaburo , Morita Takashi , Tsuda Kinsuke , Imura Hiroo
Published: December 2008

Abstract. Polymorphism of 5' portion of the human insulin gene was examined in 188 unrelated Japanese subjects (49 normal, 71 with IDDM, and 68 with NIDDM) using restriction endonuclease analysis. Restriction fragments were classified according to the insertion size: Class 1 (600 base pairs), Class 2 (1300 base pairs), and Class 3 (2000 base pairs). We found a very high frequency of Class 1 alleles (96.8%) and a low frequency of both Class 2 (0.8%) and Class 3 alleles (2.4%) and that approximately 94% of the genotypes were Class 1/Class 1 homozygote. In addition, there was no correlation of allelic or genotypic frequency with NIDDM or IDDM. We conclude that length polymorphism of the human insulin gene cannot be a useful marker for diabetes in Japanese.
Glucagon and somatostatin secretion from the perfused splenic bulb of duck pancreas
Authors: Laurent F. , Karmann H. , Gross R. , Strosser M. T. , Mialhe P.
Published: December 2008

Abstract. Glucagon, somatostatin and insulin secretions were evaluated in a new type of perfusion preparation: the naturally A and D cell rich splenic bulb of duck pancreas. Stable basal levels were observed with 11 mm glucose, corresponding to normoglycaemia, and all secretions were stimulated by 1 mm 3-isobutyl-1-methyl xanthine and by 10 mm arginine, demonstrating the technique's validity. In the absence of aminoacids in the perfusion medium, A cell blindness to glucose was corrected by physiological levels of insulin (2 ng/ml); insulinodependency of A cells, and unresponsiveness of D cells to glucose, probably not ruled by insulin, were observed. However, in the presence of aminoacids, glucagon was inhibited and somatostatin secretion stimulated by glucose (33 mm), independently of insulin (2 ng/ml). Aminoacids greatly influenced pancreatic hormone release.
The effect of sodium depletion and potassium loading on cortisol induced hypertension in sheep
Authors: Mills Eric H. , Coghlan John P. , Denton Derek A. , Spence Campbell D. , Whitworth Judith A. , Scoggins Bruce A.
Published: December 2008

Abstract. Glucocorticoid induced hypertension has been regarded as independent of sodium (Na), in contrast to mineralocorticoid induced hypertension, which is Na+-dependent. These studies compare the effect of Na+ depletion and potassium (K+) loading on glucocorticoid hypertension induced by cortisol in conscious sheep. Cortisol (480 mg/d) for 5 days, in sheep on a normal chaff diet (90–140 mmol/d Na+, 200–250 mmol/d K+) increased mean arterial pressure by 18 mmHg on day 5, increased plasma Na+ concentration, reduced plasma K+ concentration, and did not change urinary Na+ excretion. Following Na+ depletion (Na+ loss 603 ± 49 mmol), cortisol increased mean arterial pressure from 70 ± 1 mmHg to 76 ± 3 mmHg on day 5 (P < 0.001) and the increase in pressure was significantly less than the increase seen on the normal diet (P < 0.05). Plasma Na+ increased and plasma K+ decreased. Urinary Na+ and K+ excretion was unchanged. KCl loading (700–900 mmol/day) for 10 days had no effect on the maximum rise in mean arterial pressure (+18 mmHg with cortisol in K+ loaded sheep). Plasma Na+ and K+ fell, and urinary Na+ excretion increased during the infusion. These studies show that Na+ depletion, but not KCl loading, reduced cortisol induced hypertension in sheep. These data show that glucocorticoid hypertension is not independent of Na+ status.
C-peptide immunoreactivity and insulin content in the diabetic human pancreas and the relation to the stability of diabetic serum glucose level
Authors: Tasaka Yoshimasa , Marumo Koji , Inoue Yukiko , Hirata Yukimasa
Published: December 2008

Abstract. The content of insulin and C-peptide-like immunoreactivity (CPR) were determined in the tail of pancreas from 35 autopsied diabetic and 21 non-diabetic subjects. In the 28 diabetics who had been followed for more than 6 months, the relation between the amount of insulin or CPR in the pancreas and the stability of fasting serum glucose during diabetic life before death was analyzed together with the relation between the serum CPR response to the breakfast tolerance test before death and insulin content at autopsy. As an index of the instability of the blood sugar level, the standard deviation of the mean of 15 successive determinations of fasting serum glucose was used. Both insulin and CPR content in the pancreas were significantly decreased in diabetics as compared with non-diabetics. sd of the mean fasting serum glucose and insulin or CPR content in the tail of pancreas showed a significant inverse correlation on a logarithmic scale (P < 0.01, r = −0.704 and P < 0.01, γ = −0.757, respectively). Serum CPR value during the breakfast tolerance test correlated significantly with the insulin content in the pancreas of diabetic subjects. These findings suggest that one of the causes of the instability of fasting serum glucose levels is the devastation of pancreatic β-cells and that the pancreatic insulin content is logarithmically and inversely related to fluctuations in fasting serum glucose.
Hepatic oestrone sulphotransferase activity and plasma levels of oestrone sulphate, oestrone and oestradiol in male guinea pigs with fatty liver
Authors: Myking Ole , Lærum Ole Didrik
Published: December 2008

Abstract. Fatty liver was induced in male guinea pigs by combined administration of carbon tetrachloride and azathioprine from the 3rd to 15th week of age. The final body and liver weights were significantly lower than in the control animals, whereas the liver weight in percentage of total body weight was equal. The protein concentration in the 105 000 × g cytosol fraction from the livers was significantly lower than in controls (2P < 0.02). The oestrone sulphotransferase activity was studied by measuring the oestrone sulphate production when incubating oestron, PAPS + [35S]PAPS and liver cytosol for 1 h. Significantly less oestrone sulphate per mg protein, per gram liver tissue or total liver was produced with cytosol from animals with fatty liver than from controls (2P < 0.02). In accordance with decreased oestrone sulphotransferase activity, animals with fatty liver revealed significantly lower plasma levels for oestrone sulphate (2P < 0.02), whereas the plasma levels for oestrone and oestradiol were increased (2P < 0.02). The present study supports the assumption of decreased oestrone sulphotransferase activity being important for the changes in plasma oestrogens seen in alcoholic men with fatty liver.
Catecholamines and opioid peptides in human phaeochromocytomas
Authors: Yanase Toshihiko , Nawata Hajime , Kato Ken-ichi , Ibayashi Hiroshi
Published: December 2008

Abstract. The tissue contents of catecholamines (CAs) and methionineenkephalin-like immunoreactivity (Met-enk) were examined in 8 patients with phaeochromocytomas (Phs). In 6, Ph cells were cultured, and the modes of secretion of CAs and Met-enk were examined. Tissue contents of CAs and Met-enk varied from patient to patient, but larger amounts of Met-enk were found in medullary Phs than extramedullary ones, regardless of the secreting CA type. Three patients with extramedullary Phs had clinically showed a sustained hypertension, whereas five with medullary Phs were normotensive or had occasional paroxysmal hypertension. Nicotine (10−7 m to 10−4 m) stimulated simultaneous secretion of CAs and Met-enk from the cultured human Ph cells. Met-enk, however, was not secreted in proportion to either epinephrine (E), norephinephrine (NE) or total CAs (E + NE). Met-enk, FK33–824 (FK) (Met-enkephalin analogue), and dynorphin 1–13 (Dyn) significantly suppressed the secretion of CA evoked by 10−5 m nicotine. The 50% inhibitory concentrations IC50) of Met-enk, FK, and Dyn were 5 × 10−6 m, 9.9 × 10−5 m, and 9.0 × 10−8 m, respectively, in one patient and 9.0 × 10−6 m, 1.5 × 10−7 m, and 1.4 × 10−7 m in another. In one patient, 10−5 m naloxone inhibited the CA secretion evoked by 10−5 m nicotine and did not reverse the 10−5 m FK-induced suppression of CA secretion in the presence of 10−5 m nicotine. These results suggest that human Phs may be heterogenous with regard to storage and secretion of CAs and opioid peptides. The differences in the tissue content of opioid peptides and the suppressive effect of opioid peptides on the CA secretion may play an important role in clinical manifestations such as hypertension.
In vivo evidence for dopaminergic regulation of the canine pituitary intermediate lobe
Authors: Kemppainen R. J. , Sartin J. L.
Published: December 2008

Abstract. In order to examine regulation of pituitary intermediate lobe secretion, plasma immunoreactive (i)ACTH, cortisol, and α-MSH responses to iv bolus injections of CRF, quipazine maleate (serotonin agonist), isoproterenol (β-adrenergic agonist) or haloperidol (dopamine antagonist) were determined in conscious, unrestrained dogs. Endocrine responses to these test substances were also determined in dogs pre-treated with dexamethasone. Administration of one or more doses of each test substance resulted in significant elevations in plasma iACTH and cortisol concentrations. Only haloperidol injection caused significant increases in plasma iα-MSH. Following dexamethasone pre-treatment, plasma iACTH and cortisol increases in response to all test substances were considerably reduced or abolished. Dexamethasone did not alter baseline or haloperidol-stimulated plasma ia-MSH concentrations. However, infusion of bromocriptine mesylate (dopamine agonist) in combination with dexamethasone pre-treatment reduced the plasma iα-MSH response to haloperidol. We conclude that a dopaminergic pathway is important in the in vivo regulation of pituitary intermediate lobe activity in dogs.
Changes in the responsiveness of perifused rat adenohypophysial cells to repeated stimulation with luteinizing hormone releasing hormone
Authors: Buckingham Julia C. , Cover Patricia O.
Published: December 2008

Abstract. The ability of luteinizing hormone releasing hormone (LRH) to stimulate the release of luteinizing hormone (LH) from columns of enzymatically dispersed perifused adenohypophysial cells is being used to study the mechanisms controlling the secretion of LH. LRH stimulated the release in vitro of LH from columns of rat pituitary cells. However, when exposed repeatedly (1 pulse every 12 min) to the same submaximal dose (8 nmol/l) of LRH the cells always exhibited a marked progressive increase and subsequent decrease in their responsiveness. Similar effects occurred when the interval between pulses was extended to 20, 30 or 45 min. The enhanced responsiveness of the cells was prevented by the inclusion of protein synthesis inhibitors, cycloheximide or puromycin, in the perifusion fluid. Cells removed from rats ovariectomized 14 days previously also failed to exhibit increased responsiveness when stimulated repeatedly with LRH. LH secretion was also elicited by K+ (50 nmol/l), 8-bromoadenosine 3′-5′-cyclic monophosphate (8-Br-cAMP, 6 nmol/l), 8-bromoguanosine 3′-5′-cyclic monophosphate (8-Br-cGMP, 6 nmol/l) and a calcium ionophore (A23187, 40 μmol/l) but the responses to these secretagogues differed markedly from those to LRH for the tachyphylaxis which resulted from repeated exposure was not preceded by an increase in responsiveness. The decreased responsiveness to K+ developed in parallel with that to LRH. Diminished responses to the cyclic nucleotides and the Ca++ ionophore developed more rapidly, but the refractory cells responded readily to stimulation with LRH or K+. The results suggest that the increased responsiveness of the perifused pituitary cells induced by LRH is associated with steroid-dependent protein synthesis and that the secretion of LH elicited by its releasing hormone does not involve cAMP or cGMP.
Immunity in Graves' disease at diagnosis: correlation between activated T cells and humoral immune factors
Authors: Di Mario U. , Scardellato A. , Irvine W.J. , Kennedy L. , Kadlubowski M. , Kennedy R. , Cavatorta F. P. , Andreani D.
Published: December 2008

Abstract. Activated T cells, T-cell subsets, thyrotropin receptor antibodies and immune complexes were evaluated in 31 patients with newly diagnosed Graves' disease. Activated T cells were assayed by monoclonal antibodies against early (4F2) and late activation surface lymphocyte antigens (different epitopes of class II antigens). In comparison with the normal population, Graves' patients showed a significant decrease in the suppressor cytotoxic T-cell subset. Significant increases of 4F2-positive cells (70% of patients studied), class II antigen-positive cells (65%), thyrotropin receptor antibodies (93%), Clq-immune complexeses (44%) and conglutinin-immune complexes (37%) were observed. A significant inverse correlation between the increase in 4F2-positive cells and thyrotropin receptor antibody values was also observed. Lymphocytes from Graves' patients were cultured in the presence of thyrotropin receptor antibody-positive or -negative sera, with or without mitogen stimulation. Thyrotropin receptor antibodies were shown not to interfere with the expression of activation antigens in cultured cells. The different patterns of humoral and cellular immune phenomena may indicate the existence of either different stages of Graves' disease or a heterogeneity of the immunopathogenesis in different patients.
The prevalence of immunological abnormalities in endemic simple goitre
Authors: Grubeck-Loebenstein B. , Kassal H. , Smyth P. P. A. , Krisch K. , Waldhäusl W.
Published: December 2008

Abstract. Thyroid growth stimulating immunoglobulins microsomal antibodies and antibodies against thyroglobulin were determined in patients with simple goitre (n = 20) and controls (n = 6) living in an iodine deficient area. In addition, lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T-cells as well as B1+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal T-lymphocytes were examined. Goitrous patients were subdivided into two groups according to their individual iodine supply estimated by iodine excretion values, and immunological parameters were compared between patients with low (group A, iodine excretion < 70 μg/24 h) and with higher (group B, iodine excretion> 100 μg/24 h) iodine supply. Thyroid growth stimulating immunoglobulins and antithyroid antibodies were equally prevalent in the two patient groups, but were absent in controls. Lymphocytic infiltration of thyroid tissue was present to a comparable extent in patients of groups A and B, but to a distinctly lower degree in control persons. Intrathyroidal T-lymphocyte subsets did not differ between patients and controls. B-lymphocytes, germinal centres as well as DR+ thyrocytes were detected in goitrous patients of both groups, but never in control persons. Thus, immunological abnormalities frequently occur in patients with simple goitre and do not depend upon individual iodine supply.
Thyroid hormone-catecholamine interrelationship during cold acclimation in rats Compensatory role of catecholamine for altered thyroid states
Authors: Sato Tamotu , Imura Eiichi , Murata Akisato , Igarashi Noboru
Published: December 2008

Abstract. Effects of hyper- and hypothyroidism on catecholamine (CA) metabolism in the brain, adrenal glands, liver, and brown adipose tissue (BAT) were studied in adult rats during cold acclimation. Hypothyroidism was induced by the administration of propylthiouracil (PTU) and hyperthyroidism by the injection of thyroxine (T4). After 2 weeks of treatment, they were exposed to cold (5°C) and sacrificed after 1 or 4 weeks. Although the body weight gain of PTU-treated rats were markedly impaired, the body temperature was maintained within normal range. They had increased cerebral dopamine, adrenal CA and BAT norepinephrine (NE) contents, enhanced cerebral tyrosine hydroxylase and adrenal dopamine β-hydroxylase (DBH) activities and elevated [3H]dihydroalprenolol (DHA) binding to liver plasma membranes (P <0.01 vs controls). T4-treated rats showed an increased brain and adrenal CA only after cold exposure. The BAT NE content, DHA binding to liver plasma membranes, and [3H]guanosine diphosphate binding to BAT mitochondria were reduced by 30 to 50% from control values after 4 weeks of cold exposure. These results indicate that during cold acclimation, 1) thyroid hormone deficiency is associated with an accelerated CA synthesis and release, which results in an enhanced BAT thermogenesis, and 2) the hyperthyroid state suppresses CA release, hepatic DHA binding, and BAT heat production. Thus, there is a close metabolic interrelationship between thyroid hormone and CA during exposure to cold. CA appears to ameliorate thyroid hormone excess or deficiency.
Parathyroid hormone release in vitro in hyperparathyroidism associated with multiple endocrine neoplasia type 1
Authors: Benson Lars , Rastad Jonas , Ljunghall Sverker , Rudberg Claes , Åkerström Göran
Published: December 2008

Abstract. Hyperparathyroidism (HPT) in the syndrome of multiple endocrine neoplasia type 1 (MEN-1) exhibits a different picture regarding its propensity for recurrence compared with sporadic primary HPT. In order to shed further light on the MEN-1 syndrome an investigation in vitro was made of parathyroid hormone (PTH) release of dispersed parathyroid cell from 11 patients with parathyroid hyperplasia associated with MEN-1, 10 patients with single parathyroid adenomas, and 10 preparations of normal bovine parathyroid glands. The two patient groups had the same average serum calcium value prior to surgery. Immunoreactive concentrations of PTH were measured after 2-h incubations at extracellular calcium concentrations of 0.5–3.0 mmol/l. Compared with the normal bovine parathyroid cells, the cells of the MEN-1 patients had a reduced calcium sensitivity of the PTH release and secreted smaller amounts of hormone at both low and high extracellular calcium concentrations. A similar abnormality of the PTH release was found for the cells of the hyperplastic and adenomatous parathyroid glands. Although individual parathyroid glands were investigated in only three MEN-1 patients, the results suggested the secretory regulation to be less defective in the small glands of each patient. It is concluded that in patient groups matched for serum calcium, the parathyroid tissue of MEN-1 patients has an abnormality of the PTH release similar to that of parathyroid adenomas.
Sex-steroid-binding plasma protein (SBP), testosterone, oestradiol and dehydroepiandrosterone (DHEA) in prepuberty and puberty
Authors: Maruyama Yoshiyuki , Aoki Norihiko , Suzuki Yasuyuki , Ohno Yasuhiro , Imamura Minoru , Saika Toyohiko , Sinohara Hyogo , Yamamoto Toshio
Published: December 2008

Abstract. Measurement of sex-steroid-binding plasma protein in serum of healthy individuals in prepuberty and puberty (74 males and 94 females) was performed using a radioimmunoassay procedure. An age-related decrease of serum SBP was demonstrated during these ages in both sexes. In parallel studies, the serum level of testosterone, oestradiol and dehydroepiandrosterone was evaluated in subjects under 20 years of age. A rise of serum dehydroepiandrosterone levels in both sexes was observed to occur at approximately 8 years of age, being a little bit earlier than the ages for testosterone to rise in males and for oestradiol to rise in females, both of them being at about 10 years of age, respectively. When the testosterone/sex-steroid-binding plasma protein ratio was evaluated as an index of free testosterone concentration in serum, a sharp increase of the ratio was found to occur at 10 years of age and to continue during puberty in both sexes with more marked increment in males than in females. It was suggested that the decrease of SBP in puberty might be largely influenced by alteration in the hormonal balance of testosterone, oestradiol and dehydroepiandrosterone.
Heterogeneity of immunoreactive gastric inhibitory polypeptide in the plasma of newly diagnosed type 1 (insulin-dependent) diabetics
Authors: Krarup Thure , Holst Jens Juul , Madsbad Sten
Published: December 2008

Abstract. The aim was to compare the three molecular forms of plasma immunoreactive gastric inhibitory polypeptide (IR-GIP) i.e. void volume (Vo), 8 and 5 kDa IR-GIP, found in type 1 diabetics with those found in normal subjects. Plasma from 6 non-fasting newly diagnosed ketotic type 1 diabetics obtained before and 1 h after a test meal given at start of insulin treatment, and before and 1 h after a test meal given after one and seven days of insulin treatment, respectively, was gel filtered and so was plasma from 6 normal subjects. The immunoreactivity in the effluents was measured with five different antisera. The elution positions of the three peaks were similar in controls and diabetics. With any given antiserum none of the components differed significantly as to amount of immunoreactivity between diabetics and controls, neither after the meals nor in the fasting state. The amount of Vo did not change in response to the meal, whereas the 8 and 5 kDa forms in the diabetics increased similarly to the increase in normals, also during ketosis. The Vo component did not differ significantly between diabetic and normal subjects, but it decreased significantly after start of insulin treatment. In the non-fasting, ketotic state before start of insulin treatment, no IR-GIP form was elevated significantly above normal postprandial levels. We conclude that the molecular forms of IR-GIP are similar in type 1 diabetics and normal subjects, but the molecular forms measured and their relative amounts vary according to which antiserum is used. The present study does not support that lack of insulin and ketosis markedly influence IR-GIP in plasma.
Tamoxifen does not block the inhibitory effect of testosterone on FSH release in rats
Authors: Negri-Cesi P. , Celotti F. , Melcangi R. C. , Zanisi M. , Motta M.
Published: December 2008

Abstract. The aim of the present experiments was to analyze whether the inhibitory effect exerted by testosterone on FSH release might be mediated by the intracerebral transformation of the hormone into oestrogenic metabolites. Advantage has been taken of the availability of the potent antioestrogen tamoxifen. Two series of experiments have been performed. In the first one, adult male rats have been castrated and submitted, beginning immediately after surgery, to a 6-day treatment with testosterone propionate (2 mg/rat/day), tamoxifen (50 or 200 μg/rat/day) or testosterone propionate (2 mg/rat/day) plus tamoxifen (either 50 or 200 μg/rat/day). In the second experiment, adult male rats have been castrated and submitted to the same 6-day treatments, beginning 4 weeks following orchidectomy. In both experiments, the animals were killed 24 h after the last injection, and serum levels of FSH and LH have been measured by radioimmunoassays. The results have clearly shown that, in both experiments, the administration of testosterone results in a significant decrease of serum FSH and in a total suppression of LH release. The administration of tamoxifen, in either dose, does not modify the elevated serum FSH and LH levels present in the orchidetomized animals, and does not antagonize the inhibitory effect on FSH and LH secretion exerted by the concomitant treatment with testosterone propionate. It is concluded that testosterone inhibits FSH secretion in orchidectomized rats acting as such, and not following aromatization to oestrogens.
Dynorphin-(1-13) is a potent in vivo suppressor of vasopressin levels in the rat
Authors: Haaf Jeroen A. T. , Maigret Carla , Andringa-Bakker Els A. D. , van Wimersma Greidanus Tjeerd B.
Published: December 2008

Abstract. Intracerebroventricular administration of dynorphin-(1-13) inhibits dose-dependently plasma vasopressin level in normal as well as in water-deprived rats, whereas systemic (subcutaneous) administration of this opioid peptide is ineffective in this respect. Simultaneous subcutaneous, but not intracerebroventricular, administration of naloxone prevents the suppressive effect of dynorphin-(1-13) on plasma vasopressin levels.
The effect of nadolol on heart rate in hyperthyroidism. A controlled trial
Authors: Lazarus J. H. , Kingswood J. C. , John R.
Published: December 2008

Abstract. Twenty hyperthyroid patients were randomly assigned in a double-blind fashion to receive either nadolol 80 mg/day or placebo for 2 weeks; all patients then took carbimazole as well from 2–6 weeks. Twenty-four hour Holter ECG recordings at 0, 2 and 6 weeks showed that nadolol reduced the mean maximum heart rate by 19.9% (P < 0.0005) at 2 weeks and by 30.3% (P < 0.0005) at 6 weeks compared to 5.2% (ns) and 18.3% (P < 0.0005) in patients taking placebo. There was no alteration of the normal circadian variation of heart rate by nadolol. The minimum heart rate before therapy was significantly correlated with FT4 (r = 0.52) and with FT3 (r = 0.44). The percentage of time per hour during which the heart rate was greater than 100 was reduced by 79% at week 2 by nadolol compared to 22% in the placebo group. At the 6 week point the placebo group still had a tachycardia (mean maximum heart rate 101.6 beats/min ± 15.2 sd) compared to the nadolol group (80.4 ± 7.7). Nadolol did not cause excessive bradycardia. It is effective in the early management of hyperthyroidism and should be given for at least the first 4–6 weeks.
Comparison of two tests to recognize or exclude 5α-reductase deficiency in prepubertal children
Authors: Greene S. , Zachmann M. , Manella B. , Hesse V. , Hoepffner W. , Willgerodt H. , Prader A.
Published: December 2008

Abstract. Plasma testosterone (T, nmol/l) and dihydrotestosterone (DTH, nmol/l) were measured in 54 children and young adults with male pseudohermaphroditism (46XY, no defect of steroid biosynthesis) 4 h after im injection of testosterone propionate (25 mg/m2, group 1, N = 18), or before and 2, 4 and 6 days after hCG (5000 IU/m2 im, group 2, N = 36). The response to hCG was also studied in 5 control children (unilateral cryptorchidism, group 3) and that to testosterone propionate in a gonadectomized child with confirmed 5α-reductase deficiency. Mean T (133.1 ± 14.0, sem) and DHT (17.1 ± 2.6) in group 1 were higher than in group 2 (17.3 ± 2.1 and 2.9 ± 0.4), but there was not significant difference in the T/DHT ratios (group 1: 10.7 ± 2.0; group 2: 7.2 ± 0.6). Following testosterone-propionate, there was a negative correlation of T with age (r = −0.723). After hCG, T and DHT were lower in the prepubertal children than in those under 2 or over 10 years, and the T/DHT-ratio rose with age. Two children from group 1 had a T/DHT-ratio above 18, but urinary aetiocholanolone/androsterone (Ae/A) ratios were normal. In the child with 5α-reductase deficiency, the T/DHT ratio was 60, and the urinary Ae/A ratio high. We concluded that the two tests are suitable for confirming or excluding 5α-reductase deficiency in prepubertal children, in whom basal DHT is too low for evaluation, but that physiological age-related changes in 5α-reductase activity have to be taken into consideration.
Suppression of spermatogenesis in a nonhuman primate (Macaca fascicularis) by concomitant gonadotropin-releasing hormone antagonist and testosterone treatment
Authors: Weinbauer G. F. , Surmann F. J. , Nieschlag E.
Published: December 2008

Abstract. The effects of concomitant testosterone (T)-supplementation on gonadotropin-releasing hormone (GnRH) antagonist-induced testicular regression in cynomolgus monkeys (M. fascicularis) were investigated. Four adult monkeys were infused via osmotic minipumps with daily amounts of 2 mg of a potent GnRH antagonist (N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10)-GnRH (RS-68439) for a period of 104 days. Androgen substitution was provided via T-filled Silastic capsules implanted at initiation of GnRH antagonist treatment. Within 1–4 days of GnRH antagonist administration, serum concentrations of bioactive LH became undetectable. The implants maintained serum T at 50–80% of pre-treatment levels. Sperm production decreased in three out of four monkeys. One animal became azoospermic by the 13th week of treatment and the ejaculates of two other monkeys contained less than 5 × 106 sperm. In the fourth monkey, spermatogenesis was less affected. Testicular histology, judging from biopsies at termination of GnRH antagonist treatment, was typical of the hypogonadotropic status in 3 of the 4 monkeys. The most affected tubules contained only spermatogonia and Sertoli cells. Although comparison with GnRH antagonist treatment alone in a previous study indicated a delay of spermatogenic inhibition with testosterone, the present study confirms the potential of GnRH antagonist for male fertility regulation.
Thyroid hormone profile in dairy cattle acclimated to cold or hot environmental temperatures
Authors: Aceves C. , Romero C. , Sahagun L. , Valverde-R C.
Published: December 2008

Abstract. Milk yields and the circulating profile of T4, T3 and rT3 were assessed during three different seasons of the year, in first trimester lactating (L) and in dry (D) multiparous holstein cows acclimated to distinct weather conditions. Within the thermoneutral zone (18–28°C; 40–60% RH) and regardless of their geographical location, the thyroid hormone profile in all L-cows (n = 50) resembled the so-called euthyroid sick syndrome (T4, 43.7 ± 7.7 nmol/l; T3, 1.31 ± 0.10 nmol/l and rT3, 0.52 ± 0.08 nmol/l). In both groups of animals the T3/T4 molar ratio was similar within the entire range of climates encompassed in the study. However, both groups exhibited a significant shift in the T3/rt3 molar ratio during cold (10°C; 50%) or hot-dry (34°C; 40%) weather conditions. This shift reaches maximum values (L, 6.5 ± 1.2; D, 7.9 ± 1.0 nmoles/l) under hot-humid conditions (28–42°C; 60–90%). The relative increase of T3 levels from comfortable to cold or hot environmental temperatures, was significantly higher in L than D animals (30 vs 12%, respectively). Furthermore, only L-cows exhibited a significant decrease in the rT3/T4 molar ratio during either type of thermoregulatory demands, as well as a significant increase of T4 values under heat-acclimation. These results suggest that heat-acclimation in dairy cattle does not depress thyroid gland activity, and lend further support to the notion that adaptive thermoregulatory mechanisms in homeothermic vertebrates, involve adjustments in the peripheral monodeiodinative pathways of thyroid hormones.
Confirmation of the inhibitory influence of exogenous oxytocin on cortisol and ACTH in man: Evidence of reproducibility
Authors: Legros J. J. , Chiodera P. , Geenen V. , von Frenckell R.
Published: December 2008

Abstract. The influence of low-dose oxytocin perfusion (32 mIU/min) on ACTH and cortisol plasma levels was tested in 8 normal male volunteers (age 18–26). The 1-h oxytocin perfusion periods were preceded and followed by two 1-h saline control periods. During the first period, there was a slight ACTH concentration decrease in 4 individuals. Oxytocin perfusion induced a clear-cut plasma ACTH decrease in 7 out of the volunteers, and a slight decrease in the remaining one. During the second saline infusion, there was a marked ACTH increase in 7 out of the volunteers, and a weak increase in one (P < 0.0001). A similar pattern was observed in the plasma cortisol levels (P < 0.00001). Furthermore, a control saline perfusion was performed in 4 of the 8 volunteers and compared to the 4 corresponding oxytocin perfusion tests: the differences between the 2 sets of tests was highly significant both for ACTH (P < 0.003) and for cortisol (P <0.007). Lastly, the reproducibility of this inhibitory influence was retested in 4 volunteers: the tests were repeated under the same conditions 7 days later. There were no global differences between the 2 sets of tests either for ACTH (NS) or for cortisol (NS). ACTH and cortisol concentration fluctuations during the period between each set of tests were not significant. The following variations were measured for ACTH (NS) and for cortisol (NS). The present results confirm the inhibitory influence of low-dose oxytocin perfusion on ACTH and cortisol levels in normal males. Moreover, we demonstrate an increase at the end of the oxytocin perfusion (second control saline infusion). The reproducibility of the inhibitory effect at a one-week interval in 4 volunteers brings new argument against a non-specific stress influence on corticotroph function.