bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of pretreatment of long-term ovariectomized rats with an LRH antagonist on LH release in vitro by LRH, elevated K+ or N6-monobutyryl adenosine 3',5'-monophosphate (mbcAMP) plus theophylline
Authors: van Rees G. P. , van Dieten J. A. M.J.
Published: December 2008

Abstract. The effect of the LRH antagonist (Ac-D-p--Cl-Phe1,2,D-Trp3,D-Phe6-D-Ala10)-LRH (Org 30093) on pituitary LH release was studied, using pituitary glands of ovariectomized rats. In vitro, the antagonist had no detectable agonist activity in the concentration used, had no effect on the maximal LH release which can be induced by LRH and shifted the dose-response line of LRH to the right, without changing its slope. By this the antagonist fulfilled the conditions of purely competitive antagonist. Also, when present in vitro, the antagonist had no effect on LH release induced by raised K+, whether alone or in combination with mbcAMP plus theophylline. A single injection of Org 30093 decreased serum LH without inducing a change of pituitary LH content measured 24 h later. Twenty-four h after the sc injection of the agonist, LH release in vitro induced by LRH was affected differently, depending on the concentration of LRH used: the effect of low concentrations of LRH was inhibited, whereas the effect of high concentrations of LRH was augmented. Pretreatment with the agonist had no effect on LH release by raised K+ combined with mbcAMP plus theophylline, but slightly increased LH release by raised K+.
Effect of human growth hormone on proteoglycan synthesis in cultured rat chondrocytes
Authors: Madsen K. , Makower A.-M. , Friberg U. , Edén S. , Isaksson O.
Published: December 2008

Abstract. We have previously demonstrated that hGH stimulates DNA synthesis in cultured chondrocytes in the absence of serum. The present study is concerned with the effects of hGH on proteoglycan synthesis by cultured chondrocytes. Chondrocytes were isolated from rat rib growth cartilage by collagenase digestion, plated in plastic dishes, transferred to serum-free MCDB 104 medium, and incubated for 24 h to establish growth arrest. The cultures were then preincubated for 0–24 h with various concentrations of hGH and ovine prolactin (oPrl) and finally pulse-labelled for 30 min with radioactive sulphate in the presence of hormone. hGH, but not oPrl, stimulated sulphate incorporation with an apparent maximum at 50 ng/ml (approximately 170%). The stimulatory effect was apparent after 2 h and maximal after 3 h preincubation. After 12 h the stimulatory effect had decreased to insignificant levels. Qualitative analysis of isolated proteoglycans indicated that the stimulation of sulphate incorporation by hGH is exerted at the level of protein synthesis with little effect on glycosylation and sulphation. Further experiments are required to demonstrate whether the stimulatory effect on proteoglycan synthesis is a specific phenomenon or represents one aspect of a general stimulation on cell metabolism in preparation for DNA synthesis.
The effect of propranolol on circulating thyroid hormone measurements in thyrotoxic and euthyroid subjects
Authors: Franklyn J. A. , Wilkins M R. , Wilkinson R. , Ramsden D. B. , Sheppard M. C.
Published: December 2008

Abstract. Circulating concentrations of total and free thyroid hormones and thyroid hormone binding proteins were measured in thyrotoxic and euthyroid subjects treated with propranolol. In the thyrotoxic group, total triiodothyronine (T3) concentration fell after propranolol therapy, suggesting an effect of the drug on the peripheral conversion of thyroxine (T4) to T3. In euthyroid subjects, a rise in circulating concentrations of free T4 and reverse T3 (rT3) was observed, while only a small decrease in free T3 was evident. Thyroxine binding globulin (TBG) concentration fell during propranolol treatment while thyroxine binding prealbumin (TBPA) concentration rose. The changes observed in the euthyroid state are consistent with inhibition of peripheral deiodination of T4 and rT3; an additional effect of propranolol on binding protein metabolism was evident.
Organ culture of human foetal pancreas: conditions which affect basal and stimulated insulin release
Authors: Maitland Janice E. , Caterson Ian D. , Gauci Rebecca E. , Spaliviero Jennifer A. , Turtle John R.
Published: December 2008

Abstract. Human foetal pancreas has been maintained in organ culture with net synthesis and release of insulin for up to 60 days. The age of the donor foetus affected the basal insulin release rate. A plateau of secretion was reached with foetuses of ≥ 16 weeks of gestation. Explants cultured within 2 h of expulsion following prostaglandin induced termination secreted 3.0 times more insulin after 20 days of culture than those cultured within 2–4 h and 8.1 times more than those cultured more than 4 h post-termination. A high oxygen environment was toxic to the explants during culture.

Fresh tissue responded to a high concentration of glucose (19.3 mm) with a small but significant increase in insulin secretion. The addition of 10 mm theophylline caused a major increase in insulin release. Cultured tissue did not respond to glucose alone but did show increased insulin release following stimulation with glucose (22 mm) together with theophylline (10 mm) in static incubation.

The culture of human foetal pancreatic tissue may be useful in maintaining responsive beta cells and may help to ensure an adequate amount of donor tissue for future transplantation into diabetic patients.
Steroid secretion by cumulus cells isolated from human preovulatory follicles
Authors: Hillensjö Torbjörn , Sjögren Anita , Strander Björn , Andino Nieves
Published: December 2008

Abstract. The secretion of progesterone, testosterone, and oestradiol by intact human oocyte-cumulus complexes in vitro was examined in incubations lasting 6–24 h. The complexes were aspirated from preovulatory follicles in 32 women who, due to tubal disease, were participating in an in vitro fertilization program. In 12 of the women follicular maturation was induced with clomiphene and human chorionic gonadotrophin (hCG), in 13 women with human menopausal gonadotrophin (hMG) and hCG and in 7 women with a combination of clomiphene-hMG plus hCG. The net secretion of steroids into the fertilization medium was studied before (0-6 h) and after (6–24 h) the addition of sperm, by RIA of aliquots removed at specific times.

A high and sustained secretion of progesterone was found both before and after insemination. Testosterone secretion remained at a low and constant level while a net release of oestradiol was found mainly during the first hours of incubation. The release of steroids, particularly progesterone, varied according to the mode of hormonal stimulation in vivo and was highest in complexes from clomiphene-hMG-treated women, probably reflecting different maturity of the aspirated follicles. In a second series of experiments the dispersed cumulus cells were recovered after fertilization and cultured as monolayers for 2–4 days. The cells underwent spontaneous luteinization and secreted high amounts of progesterone.

These results extend previous work in animals showing that also in the human the periovulatory cumulus cells are steroidogenically active. The results also suggest a functional difference in the cumulus cells related to the mode of ovulation induction.
Endocrine and immunogenetic evaluation of an XX male infant with perineoscrotal hypospadias
Authors: Kofman-Alfaro S. , Valdés E. , Terá J. , Wachtel S. S. , Chávez B. , Bassol S. , Medina M. , Pérez-Palacios G.
Published: December 2008

Abstract. To clarify the origin of the genital ambiguity occasionally associated with the XX male syndrome, a series of endocrinological studies were undertaken in an affected 6 months old infant with perineoscrotal hypospadias. The patient fulfilled all the diagnostic criteria of the syndrome: the testes were descended bilaterally, the Mullerian derivatives were absent, the 46,XX chromosome complement was ascertained in different cell lines, and male levels of H-Y antigen were detected in cultured skin fibroblasts. Circulating gonadotrophin levels and pituitary LRH responsiveness were within normal limits for the age group. Serum testosterone (T) levels were normal, and gonadal stimulation with hCG caused a significant rise on serum T. Incubations of [3H]T with fibroblasts from genital skin revealed normal activity of steroid 5α-reductase. Moreover, normal concentrations of thermostable cytosol androgen receptors were revealed in cultured fibroblasts. Altogether the results indicated that ambiguity of the external genitalia in this patient was the result of neither abnormal T biosynthesis, peripheral A-ring T reduction, nor androgen intracellular specific binding, and suggested that the nature of the imcomplete virilization could be a non-endocrine independent event associated to this disorder. The data are also consistent with the notion that testicular impairment observed in adult XX males develops later in life.
Effect of long-term corticosteroid administration on rat pituitary growth hormone and prolactin
Authors: Oosterom R. , Verleun T. , Zuiderwijk J. , Uitterlinden P. , Lamberts S. W. J.
Published: December 2008

Abstract. In vitro corticosteroids stimulate GH synthesis by pituitary cells, while in vivo they suppress stimulated plasma GH levels. In this study we investigated in rats the effect of hydrocortisone administration for 2–4 weeks on pituitary GH content. Hydrocortisone added to the drinking water (100 mg/l) resulted in a marked stimulation of pituitary GH content after 3 and 4 weeks of treatment. No significant stimulation, however, was observed on basal GH release by the pituitary gland incubated in vitro. Further, we found that both Prl content and release were inhibited by hydrocortisone administration.
Comparison of histology and immunohistochemistry with thyroglobulin serum levels and radioiodine uptake in recurrences and metastases of differentiated thyroid carcinomas
Authors: Dralle Henning , Schwarzrock Rüdiger , Lang Walter , Böcker Werner , Ziegler Horst , Schröder Sören , Geerlings Heinz
Published: December 2008

Abstract. The importance of lightmicroscopical and immunohistochemical features of 38 recurrent differentiated thyroid carcinomas (27 papillary carcinomas (PC), 11 follicular carcinomas (FC)) for post-operative serum thyroglobulin (TG) concentrations was analysed in regard to pre-operative serum TG levels with tumour type, histological and cytological differentiation, volume fraction of TG synthesizing tumour cells (TG immunohistomorphometry), tumour volume and radioiodine uptake (RIU).

Serum TG concentrations increased with tumour size and the number of TG synthesizing tumour cells (r = 0.5). PC and FC did not differ in their volume proportions of TG synthesizing tumour cells, while TG serum levels in FC significantly exceeded those of PC of similar size. The low TG serum levels found in PC might be explained by a specific defect in thyroglobulin secretion. Carcinomas with partial or total cytologic metaplasia (e.g. oxyphilic carcinomas) had low volume proportions of TG synthesizing cells and low serum TG levels.

Thirteen of the 38 differentiated carcinomas (34.2%) showed both high TG serum levels and positive RIU, 17 (44.7%) disclosed only elevated TG serum levels and 6 (15.8%) a positive RIU. In two cases (5.3%) TG serum levels were not elevated and RIU's were negative. TG immunostaining was positive in all 38 cases.

In summary, TG serum levels depend on the following morphologic factors in differentiated thyroid carcinomas: 1) Number of TG synthesizing tumour cells, 2) Mode of TG secretion and 3) Cytological differentiation of the tumour cells. Serum TG levels did not predict total body iodine scan.
Functional development and maturation of the rat thyroid gland in the foetal and newborn periods: an immunohistochemical study
Authors: Kawaoi Akira , Tsuneda Minoru
Published: December 2008

Abstract. Immunohistochemical detection of T4, T3 and thyroglobulin (Tg) was undertaken in foetal and neonatal rat thyroid glands in an attempt to elucidate the functional development and maturation of the gland during these periods.

Immunoreactive Tg first appeared in the cytoplasm of the immature thyroid epithelium on the 15th day of gestation, followed by the occurrence of T4 and T3 in the lumen of primitive follicles of the thyroid gland 2 days later. The stainability of Tg, T4 and T3 increased as the follicular structure became mature; however, no significant difference in staining patterns was observed during the perinatal periods.
Comparison between the effects of FSH and LH on the steroidogenic pattern in isolated pre-ovulatory rat follicles
Authors: Carlsson Björn , Skånberg Jan-Owe , Roos Paul , Hillensjö Torbjörn
Published: December 2008

Abstract. The effects of purified FSH preparations from three different species (ovine, human, rat) on the steroidogenic pattern in isolated pre-ovulatory follicles of PMSG-treated immature rats were examined and compared to the effects of LH (ovine, human). Steroids were analyzed by RIA. During 6 h incubation, all three FSH preparations in a concentration range from 10–100 ng/ml caused a significant increase in progesterone (P), testosterone (T), and oestradiol (E2) accumulation. With LH a significant increase in steroid accumulation was seen in a concentration of 1 ng/ml. The time-course of stimulation by hFSH and hLH in a concentration of 10 ng/ml showed no difference in steroidogenic response between the two hormones, with a significant stimulation of steroids within 2 h.

During prolonged incubation (6–8 h), accumulation of T was measured in the presence or absence of unlabelled 17α-hydroxyprogesterone. Follicles exposed to LH did not increase their T formation, while follicles incubated in plain medium or in the presence of oFSH increased their T formation. In a concentration of 100 ng/ml hFSH showed a tendency to reduce maximal T production.

These results suggest that FSH alone in physiological doses may stimulate T and E2 production in the preovulatory follicle.
Serum gonadotrophin pulsatile secretion in men with Prl-secreting and non-secreting pituitary tumours
Authors: Ambrosi Bruno , Giovine Claudia , Nava Claudio , Elli Roberto , Faglia Giovanni
Published: December 2008

Abstract. In order to investigate the possible influence of prolactin (Prl) at the hypothalamic level, serum LH and FSH pulsatility was studied in 16 male patients with prolactinomas, normally LH responders to GnRH (group A): 8 of them were untreated (group A1) and 8 had undergone previous unsuccessful pituitary treatments (group A2). In 7 patients the study was repeated when serum Prl was normalized by bromocriptine treatment (group B). For comparison the secretory pattern of LH and FSH was studied in 6 male patients with non-secreting pituitary tumours (group C). All parameters of LH pulsatile secretion (i.e. arithmetic mean of the single concentration, coefficient of variation from the mean value, frequency of peaks, amplitude of pulses expressed as either absolute or per cent value) were significantly lower in patients of groups A1, A2 and C than in normal subjects and no difference was found between the three groups. Furthermore the 7 patients with prolactinomas studied both before and after bromocriptine-induced Prl normalization showed no difference in all the parameters of LH pulsatility in both conditions. No significant abnormalities of FSH secretory pattern were found in the patients of groups A1, A2, B and C in comparison to normal subjects. In all groups of patients mean serum testosterone basal levels were significantly lower than in normals, while the mean oestradiol-17β basal concentration was normal. The abnormalities in LH pulsatility found in untreated and bromocriptine-treated patients with prolactinomas and in patients with non-secreting tumours indicate an impairment of GnRH release in such patients; these findings suggest that Prl excess is not the only cause of the abnormalities in LH pulsatile secretion.
Serum growth hormone in patients with carcinoid tumours; basal levels and response to glucose and thyrotrophin releasing hormone
Authors: Öberg Kjell , Norheim Ingrid , Wide Leif
Published: December 2008

Abstract. The regulation of serum growth hormone was studied in 33 consecutive patients with carcinoid tumours; both diurnal serum GH and GH responses to an i.v. glucose load and TRH were assessed. Seventeen of the patients (52%) showed disturbed regulation of serum GH and 10 had at least two abnormal tests. Four patients had clinically overt acromegaly. The diurnal mean serum GH levels were higher (P < 0.001) in patients with carcinoid tumours than in control subjects and more than one third (41%) had levels in a range similar to that of acromegalic patients without carcinoid tumours. The disturbance in serum GH regulation might have been caused in some patient by tumour secreted growth hormone releasing factor(s) which act directly on pituitary somatotrophs, but other tumour-related non-specific stimulation must be considered. Carcinoid tumours should be considered in the aetiology of acromegaly.
Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis
Authors: Taylor Roy , McCulloch Alan J. , Zeuzem Stefan , Gray Peter , Clark Frederick , Alberti K. George M. M.
Published: December 2008

Abstract. The pattern of insulin secretion following an oral glucose load and the insulin receptor status and insulin sensitivity of adipocytes have been studied in patients with thyrotoxicosis and in matched controls. Thyrotoxic subjects showed normal basal and peak levels of serum immunoreactive insulin (peak, 69.0 ± 6.8 vs 54.3 ± 8.8 mU/l) and serum C-peptide (peak, 1.95 ± 0.13 vs 1.71 ±0.12 nmol/l for thyrotoxic and control subjects, respectively). Peak serum proinsulin was higher in the thyrotoxic group (64.8 ± 7.3 vs 39.0 ± 3.7 pmol/l; P < 0.01). Maximum specific insulin binding to adipocytes was decreased in the thyrotoxic group (1.80 ± 0.18 vs 2.62 ±0.27%; P< 0.025) and half-maximum displacement of tracer insulin was similar in the two groups, suggesting that reduced receptor number rather than reduced affinity accounted for the difference. However, adipocyte insulin sensitivity was normal as judged by half-maximal stimulation values of 13.9 ± 3.6 vs 11.4 ± 2.1 pmol/l, respectively for lipogenesis and 24.3 ± 2.2 vs 24.6 ± 3.6 pmol/l, respectively for glucose transport. Hence, thyroid hormone excess appears to affect adipocyte insulin receptor number directly, but change in receptor number is not associated with change in adipocyte insulin sensitivity in hyperthyroidism. The normal insulin secretion together with the failure to demonstrate abnormal insulin sensitivity of one of the major peripheral tissues suggests that disturbed hepatic rather than peripheral insulin responsiveness may be responsible for the glucose intolerance of hyperthyroidism.
Fate of receptor-bound human chorionic gonadotrophin in pseudopregnant rat ovaries perfused in vitro
Authors: Rajaniemi Hannu , Sogn Jan , Holmes Paul , Källfelt Björn , Janson Per Olof
Published: December 2008

Abstract. Pseudopregnant rats were injected with [125I] hCG, anaesthesized 1 h later and after cannulation of the aorta the ovaries were isolated and perfused with Gey & Gey buffer containing 0.2% BSA. The release of radioactivity was monitored for 2 h and analyzed by gel filtration. Five to ten per cent of the radioactivity was released within 2 h and represented small molecular weight peptides and iodotyrosine and [125I]hCG. Analysis of the ovarian radioactivity prior to and after perfusion revealed that virtually all hCG was receptor-bound. Loading the medium with unlabelled hCG displaced [125I]hCG from the receptor but did not enhance its degradation. Histological examination showed that the ovarian tissues were still intact after the 2 h perfusion. Immunohistochemical studies revealed a localization of the hCG at the cell periphery both prior to and after perfusion. These results provide evidence showing that the rate of internalization of receptor-hCG complexes in rat luteal cells is slow in vivo.
Metabolism of calcium and phosphorus during pregnancy and lactation in white-tailed deer
Authors: Chao Chun Chin , Brown Robert D. , Deftos Leonard J.
Published: December 2008

Abstract. The effects of pregnancy and early lactation on blood parameters were studied in 4 white-tailed does in 1981-82 and 8 in 1982-83. No year or fecundity effects (P < 0.05) were found on plasma calcium (Ca), inorganic phosphorus (P), calcitonin (CT), parathyroid hormone (PTH), or oestradiol -17β (E2). An increase (P < 0.05) in dry matter and metabolic feed intake occurred during pregnancy and lactation. Plasma Ca tended to increase during pregnancy and peaked 5–7 weeks pre-partum, while hypocalcaemia was observed 1–2 weeks pre-partum. Elevated concentrations of plasma Ca and P were found during lactation. During the last trimester of pregnancy, plasma concentrations of alkaline phosphatase (AP), PTH, and E2 but not of CT were higher (P < 0.05) than in the other trimesters. The results indicate a physiological hyperparathyroidism in pregnant deer. Plasma concentrations of CT were higher (P <0.05) during lactation and post-weaning than during pregnancy. Increased AP and PTH during late pregnancy may be responsible for Ca absorption and mobilization, whereas elevated plasma concentrations of E2 may function to block excessive bone resorption. After parturition, lowered E2 may allow bone resorption to proceed, relatively high PTH may enhance Ca absorption and mobilization, and elevated CT may protect the skeleton against excessive bone resorption.
Plasma sex hormone binding globulin concentration and binding capacity in children before and during puberty
Authors: Lee Ian R. , Lawder Linda E. , Townend David C. , Wetherall John D. , Hähnel Roland
Published: December 2008

Abstract. The steroid binding capacity and concentration of plasma sex hormone binding globulin have been compared in 116 children aged between 2 and 14 years. Concentration was measured by electroimmunodiffusion standardised with reference to the mass of the pure protein and binding capacity by quantitating the binding of radiolabelled 5α-dihydrotestosterone. Binding capacity correlated highly with concentration in all subjects and neither differed significantly between the sexes before or during puberty. However, both were significantly lower in pubertal than in pre-pubertal children. These findings suggest the metabolism of the protein is similar in boys and girls and that the fall in its steroid binding capacity at puberty in fact is due to a fall in its concentration rather than to changes in its physicochemical properties.
Evidence of a circulating growth hormone stimulating factor other than growth hormone releasing hormone in a patient with pituitary tumour and acromegaly
Authors: Hulting A.-L. , Wersäll J. , Werner S.
Published: December 2008

Abstract. This study is a report on the growth hormone (GH) stimulatory effect of serum and plasma from a patient with notably active acromegaly due to a GH producing pituitary adenoma.

Pituitary adenomatous tissue from 7 patients with GH producing adenomas, one with a prolactin (Prl) producing adenoma, one with a TSH producing adenoma, and one with a non-secreting adenoma, were cultured in vitro for 8–10 days. Media were changed every 48–72 h and contained Neumann Tytell buffer with the addition of 1) foetal calf serum, 2) patients' own serum or plasma, 3) serum or plasma from the patient with notably active acromegaly.

GH release expressed as μg GH/I/48–72 h between day 6 and 8 in culture did not differ when adenomatous tissue was cultured in buffer, foetal calf serum or the patients' own serum or plasma. In contrast, GH release was increased in 9/10 patients, when media contained serum or plasma from the patient with notably active acromegaly. This GH stimulatory effect was demonstrated in vitro in human pituitary adenomatous tissue from patients with pathological as well as normal GH secretion in vivo. Furthermore, this GH releasing plasma in a concentration of 10% increased GH release in cultures of dispersed rat anterior pituitary cells. In the same system, synthetic growth hormone-releasing hormone (GRF)-44 stimulated the release of GH in a dose-dependent manner. However, at all dose levels including maximally stimulating doses of GRF, an additive effect on GH release was seen with 10% of the GH releasing plasma.

These results indicate that plasma from a patient with acromegaly increases basal GH release from human pituitary adenomatous tissue and also increases basal as well as stimulated GH release from rat anterior pituitary cells in vitro. The additive effect on maximally GRF stimulated GH release, implies that the GH releasing plasma stimulates GH release at least partly by a mechanism different from that of GRF. Furthermore, these results suggest that extrapituitary factors other than GRF are involved in the release of GH from pituitary tumours.
Divergent effects on LH and FSH synthesis and release from intact female rat pituitary glands in vitro by methylxanthines, cyclic AMP derivatives and sodium fluoride
Authors: Jenner A. A.J. , de Koning J. , Tijssen A. M. I. , van Rees G. P.
Published: December 2008

Abstract. FSH release from the female rat pituitary gland consists of an LH-like, LRH-dependent component and an autonomous, inhibin-sensitive component. It was investigated whether cyclic AMP mediated FSH release. BrcAMP, theophylline, MIX or NaF stimulated LH release but inhibited FSH release and synthesis. Although dbcAMP had no inhibitory effect on FSH release, it partly reversed the inhibitory action of theophylline. In view of previous and the present results it is concluded that cyclic AMP may mediate the LRHdependent LH and FSH release and, through a separate pathway, may mediate the inhibition of autonomous FSH release by the ovarian protein inhibin.
Early effect of thyroid hormone on cytosolic protein phosphorylation in rat anterior pituitary
Authors: Nakamura Hirotoshi , Yokota Toshihiko , Imura Hiroo , DeGroot Leslie J.
Published: December 2008

Abstract. The effect of T3 was studied on phosphorylation of cytosolic proteins in rat anterior pituitary. Cytosols obtained from hypothyroid (H) and T3 (50 μg/100 g body weight) injected H rats (T) were phosphorylated in vitro. Although total incorporation of 32P into proteins did not differ between H and T, analysis of phosphoproteins by SDS polyacrylamide gel electrophoresis and autoradiography revealed that T3 injection significantly increased phosphorylation of 2 proteins within 1 h. These results and our previous demonstration of T3 effects on phosphorylation in rat liver cytosol and cultured human skin fibroblasts suggest that protein phosphorylation is an important early intracellular process in T3 action.
Orbital decompression in endocrine exophthalmos of Graves' disease
Authors: Lamberg B.-A. , Grahne B. , Tommila V. , Pelkonen R. , Rinne J. , Liesmaa M. , Välimäki M.
Published: December 2008

Abstract. Transantral decompression was performed bilaterally in 27 and unilaterally in 3 patients with endocrine exophthalmos of Graves' disease. In 28 patients there was an immediate reduction of proptosis and in about half of the patients in addition a marked decrease in chemosis and conjunctival injection indicating that these signs were mostly due to orbital vascular congestion. In one patient with exophthalmos of more than 2 years duration and progressive swelling of the eye muscles no response was observed. In another patient decompression did not reduce proptosis which, however, 4 months later responded to retrobulbar irradiation. In one further patient much more marked reduction of proptosis and disappearance of persistent periorbital swellings were obtained after glucocorticoid treatment given half a year after decompression. Postoperatively diplopia occurred in about half of the patients but corrective operations were required only in a quarter of the patients.

Transantral decompression is an effective method for rapid treatment of progressive exophthalmos of Graves' disease. In patients with unilateral exophthalmos the asymmetry may be reversed after unilateral operation. The authors use decompression not only in the most severe cases (categories 5 and 6a–c according to the classification of the American Thyroid Association) but also in less severe cases (categories 2b–c and 3b–c) when there is a steady progression as a primary treatment possibly combined with other forms of therapy.
Effect of propionate infusion on plasma glucagon, insulin and growth hormone concentrations in lactating dairy cows
Authors: Sartin J. L. , Cummins K. A. , Kemppainen R.J. , Carnes R. , McClary D. G. , Williams J. C.
Published: December 2008

Abstract. Altered concentrations of metabolic hormones have been suggested as important mediators of energy partitioning during early lactation. This study was initiated to determine the effects of propionate (1.0 mmol/kg body weight) infusion on plasma concentrations of glucagon, insulin, growth hormone, propionate and glucose at 14 days ante-partum (AP) and days 5 and 30 postpartum (PP). No differences were seen in propionate concentrations between sampling days. Glucose concentrations were elevated following propionate infusion in pregnant cows but were not elevated in the PP cows. Insulin responses to propionate infusion did not differ between days while the glucagon response was blunted at day 5 PP. Basal glucagon concentrations were elevated between days 5 and 30 PP, insulin concentrations were unchanged between days, while the molar insulin/glucagon ratio was decreased during early lactation. Basal growth hormone (GH) concentrations were elevated between day 14 AP and day 30 PP. GH responsiveness to declining propionate concentrations was greatest at day 5 PP. These data further suggest a role for glucagon as well as GH in nutrient partitioning during early lactation.
Influence of thiol groups, calcium, and glucose metabolism on cholinergic-induced insulin release and on methylscopolamine binding to muscarinic receptors in pancreatic islets of the rat
Authors: Grill V. , Fåk K.
Published: December 2008

Abstract. Short-term regulation of [3H]methylscopolamine binding to muscarinic receptors and acetylcholineinduced stimulation of insulin release was investigated in pancreatic islets of the rat. Binding of methylscopolamine was reversible; 47% of label was displaced 10 min and 70% 30 min after addition of unlabelled substance. 0.1 mm chloromercuribensoic acid, when present during binding incubations, inhibited binding by 54%, whereas acetylcholine-induced insulin release was unaffected by the presence of the thiol reactant. Pre-incubation for 60 min in a calcium-deprived medium or in the presence of 50 μm trifluoroperazine likewise inhibited binding. Pre-incubation with 1.0 mm 3-isobutyl-l-methylxanthine or 16.7 m glucose failed to influence subsequent binding although acetylcholine-induced insulin release was 4-fold enhanced by priming with glucose. We conclude that 1) binding to muscarinic receptors is influenced by thiol interaction, 2) short-term alterations in calcium fluxes influence binding, whereas short-term changes in cyclic AMP (cAMP) or glucose metabolism do not, 3) a priming effect of glucose on insulin secretion is not mediated by changes in receptor binding.
Decrease in serum sex hormone binding globulin during human chorionic gonadotrophin stimulation in prepubertal boys
Authors: Dunkel L.
Published: December 2008

Abstract. Temporal relationships between steroidogenic and sex hormone binding globulin (SHBG) responses to hCG were studied in 27 prepubertal boys: 19 with incomplete testicular descent and 8 with hypogonadotrophic hypogonadism (HH). Nine of the boys with incomplete testicular descent were given a single im injection of hCG and blood samples were taken daily for 5 days. Six of them showed a slight decrease in SHBG concentration by day 5. All the other 18 boys were given four im injections of hCG on days 0, 4, 7 and 10. Blood was taken before each injection and on day 14. In the boys with incomplete testiscular descent SHBG concentration decreased by day 14 (P < 0.01). All the boys with HH had an impaired testosterone response to hCG, and SHBG levels did not decrease after hCG. In only 2 of these boys SHBG concentrations were > 10% below the basal by day 14. These boys, however, also had the highest testosterone responses of their group. Thus it appears that if testosterone increases in prepubertal boys, SHBG decreases.
Central hyperglycaemic effect of adrenaline and carbachol
Authors: Iguchi A. , Matsunaga H. , Gotoh M. , Nomura T. , Yatomi A. , Sakamoto N.
Published: December 2008

Abstract. The effect of chemical stimulation of the brain on glucoregulation was studied in anaesthetized rats. Adrenaline, noradrenaline, acetylcholine, dopamine and carbachol (5 × 10−8 mol/μl saline) were injected directly into the third cerebral ventricle and changes in hepatic venous plasma glucose, immunoreactive glucagon and insulin concentrations were studied.

The injection of adrenaline and carbachol into the third cerebral ventricle resulted in a marked hyperglycaemia associated with increased immunoreactive glucagon. Adrenaline-induced hyperglycaemia was not affected by bilateral adrenalectomy, while carbachol-induced hyperglycaemia was completely inhibited by adrenalectomy.

The injection of somatostatin (1 × 10−9 mol) with adrenaline into the third cerebral ventricle did not influence adrenaline-induced hyperglycaemia, while carbachol-induced hyperglycaemia was inhibited by co-administration with somatostatin.

These results suggest that adrenergic and cholinergic neurons in the central nervous system may increase hepatic glucose output by different mechanism.
Aminoglutethimide and metyrapone in the management of Cushing's syndrome
Authors: Thorén M. , Adamson U. , Sjöberg H. E.
Published: December 2008

Abstract. Fifteen patients with endogenous Cushing's syndrome were treated with metyrapone and/or aminoglutethimide. The duration of the therapy varied from 19 up to 365 days. In patients with Cushing's disease, metyrapone (0.5–2.5 g/day) and aminoglutethimide (0.5–1.5 g/day) seemed equally effective in reducing the cortisol excretion (54 ± 9 vs 40 ± 7%). The majority of these patients also showed a clinical improvement. In 1 patient with adrenal adenoma, metyrapone induced a remission. In another patient with adrenocortical cancer, and in 2 with the ectopic ACTH syndrome, the cortisol excretion was significantly reduced by the combination of metyrapone and aminoglutethimide but no obvious clinical improvement was observed. Side effects i.e. rash and pruritus attributed to aminoglutethimide was seen in 3 patients which necessitated the omission of treatment in 2. On metyrapone a moderate hypertrichosis was observed in 1 patient.

In conclusion both metyrapone and aminoglutethimide were useful as adjunctive therapy in Cushing's syndrome.
Effect of pretreatment of long-term ovariectomized (OVX) rats with a competitive LRH antagonist on FSH release in vitro
Authors: van Dieten J. A. M. J. , van Rees G. P.
Published: December 2008

Abstract. The effect of a single sc injection of an LRH antagonist ((Ac - D - p - Cl - Phe1,2,D-Trp3,D-Phe6,D-Ala10)-LRH, Org 30093) into OVX rats on FSH release 24 h later was studied. Plasma FSH was decreased but pituitary FSH content was not changed. Incubation of the pituitary glands during 4 h resulted in a decreased basal release. FSH release induced by a low concentration of LRH (1 ng/ml) was depressed but that of a high concentration (10000 ng/ml) was augmented in comparison to FSH release induced in control glands. However, pretreatment with the antagonist had no specific effect on FSH release in vitro induced by high K+ or high K+ plus mbcAMP and theophylline, indicating that the changes of pituitary responsiveness to LRH are not caused by those parts of the secretory mechanism which are stimulated by these secretagogues. Moreover, it is concluded that the changes of pituitary LH release induced by administration of an LRH antagonist also concern FSH.
Cold reactive lymphocytotoxic activity in autoimmune thyroid disease
Authors: Ryan Marilyn , Sridama Vitaya , DeGroot Leslie J.
Published: December 2008

Abstract. An increased incidence of cold-reactive lymphocytotoxic activity (LCTA) has been demonstrated in the sera of patients with autoimmune thyroid disease. Twenty-six of 79 (33%) patients with Graves' disease and 9 of 21(43%) patients with Hashimoto's thyroiditis had cold-reactive LCTA detected by microcytotoxicity assay compared to 6 of 42 (14%) normal controls. There was no correlation between LCTA and age, sex, MCHA titre or TGHA titre. A positive correlation with FTI and LCTA in Hashimoto's patients was demonstrated, but no such correlation was demonstrable in Graves' patients. The lymphocytotoxic activity was directed preferentially against B cells. There was no preferential lysis of T-cell subsets as defined by monoclonal antibodies, and the lymphocytotoxins were equally reactive with normal lymphocytes and toxic Graves' lymphocytes. The significance of cold-reactive lymphocytotoxic activity in the pathogenesis of autoimmune thyroid disease remains to be determined.
VIP stimulation of β-naphthylamidase activity in guinea-pig thyroid sections
Authors: Ealey P. A. , Marshall N.J. , Ekins R. P.
Published: December 2008

Abstract. Subsequent to the discovery of vasoactive intestinal peptide (VIP) in the thyroid gland, VIP has been shown to stimulate various thyroid functions. The site of interaction of VIP with the thyroid follicular cell is at present not known, and this study has used the ultrasensitive cytochemical bioassay (CBA) for thyroid stimulators to investigate this further. Exposure of thyroid sections for 3 min to VIP resulted in increased naphthylamidase activity, with half-maximal response observed at 3 × 10−13 m VIP. This response to such low doses of VIP is consistent with the CBA being ultrasensitive to other thyroid stimulators e.g. TSH, thyroid stimulating antibodies and forskolin. The response to VIP was abolished by rabbit anti-VIP antiserum. The dose-response curve to VIP was bell-shaped (as with the other stimulators), maximal stimulation occurring at 10−12 m VIP. In contrast, however, to other thyroid stimulators, namely TSH, LATS-B and 3 monoclonal stimulating antibodies, whose ascending limbs of the doseresponse curves extended over 3-4 orders of magnitude, the VIP curve rose rapidly from basal to maximal tissue stimulation from 10−13 to 10−12m VIP, i.e. one order of magnitude. This unusual dose-response curve to VIP was parallel to that produced by forskolin. 11E8, a monoclonal 'blocking' antibody which is a potent inhibitor of TSH stimulation, did not 'block' forskolin stimulation, consistent with the belief that forskolin acts at a post-receptor site. However, unlike forskolin, VIP was inhibited by monoclonal 11E8, which may imply a hitherto unexpected involvement of the TSH receptor in VIP stimulation of the thyroid or, alternatively, steric inhibition by 11E8 when bound to the TSH receptor of VIP interaction with adjacent VIP-specific receptors.
Cyproterone acetate as initial treatment and maintenance therapy for hirsutism
Authors: Holdaway I. M. , Croxson M. S. , Ibbertson H. K. , Sheehan A. , Knox B. , France J.
Published: December 2008

Abstract. Thirty-four patients with hirsutism were treated for 9 months with 100 mg cyproterone acetate (CA) given on days 5–15 of the menstrual cycle together with a combination oral contraceptive containing 2 mg CA and 50 μg ethinyloestradiol (Diane®) given on days 5–25 of the cycle. After 9 months treatment patients were randomised to a 12 month double-blind cross-over trial comparing Diane® plus 25 mg CA with Diane® plus placebo, to test the efficacy of low-dose CA as maintenance therapy. Thirty-one patients (92%) experienced moderate or good subjective improvement in hirsutism on high-dose CA, associated with a 40% mean overall improvement in objective hirsutism grade and 13% overall reduction in hair growth rate measured by a photographic technique. Minor or moderate side effects were experienced by 64% of patients and severe side effects by 11% at this dosage. There was a mean subjective relapse rate of 33% when patients were changed to low dose CA, and relapse rates were not significantly different between the two regimens with 28% relapsing on 25 mg CA + Diane® and 48% on placebo and Diane® (P < 0.05). Despite significant subjective relapse with low-dose treatment there was no significant deterioration in objective hirsutism grade or hair growth rate determined photographically. Levels of plasma testosterone, sex hormone binding globulin, free testosterone (derived) and androstenedione fell significantly on high dose CA and this reduction was maintained during low dose therapy. Cyproterone acetate at high dosage thus appeared an effective agent in the treatment of hirsutism, but 33% of patients considered they deteriorated when changed to low-dose therapy despite maintenance of androgen suppression and lack of change in objective measurements. Maintenance therapy after remission with high-dose CA appears justified since 60% of patients underwent subjective relapse when all treatment was stopped.
Oxytocin determination in steroid producing tissues and in vitro production in ovarian follicles
Authors: Schams D. , Kruip Th. A. M. , Koll R.
Published: December 2008

Abstract Immunoreactive oxytocin was measured in ovaries (corpus luteum and follicular fluid) and adrenals of cows, and in testes, seminal vesicles, prostate gland and adrenals of bulls. Secretion of oxytocin was further measured after culture of whole follicles, granulosa cells and theca tissue. Concentrations of oxytocin increased in corpora lutea of cycling cattle until mid-luteal phase (447 ± 93 ng/g wet weight) and decreased afterwards. Low concentrations were found in corpora lutea of pregnant animals (6 ± 3 ng/g wet weight). Follicular fluid contains some oxytocin (on average 42–108 pg/ml) but concentrations were significantly higher in the fluid of ovarian cysts (190 pg/ml). After culture of follicles the amount of oxytocin released into the medium increased indicating de novo synthesis. The granulosa cells were the main source of follicular oxytocin. Production increased during luteinization indicating that luteinization is an important step for the production of oxytocin in ovaries. Tissues of testes (65 ± 10 pg/g wet weight) and adrenals from cows (122 ± 39 pg/g wet weight) and bulls (111 ±2 pg/g wet weight) contained oxytocin but at much lower concentrations compared to corpus luteum tissue. About 10 times higher concentrations of oxytocin were measured in the adrenal medulla (717 ± 96 pg/g wet weight) compared to the cortex (72 ± 11 pg/g wet weight). Seminal vesicles and prostate gland contained no measurable amounts of oxytocin (< 5 pg/g wet weight).
Interactions of an anti-androgen (cyproterone acetate) with the androgen receptor system and its biological action in the rat ventral prostate
Authors: Huang J. K. , Bartsch W. , Voigt K.-D.
Published: December 2008

Abstract. Male Wistar rats were castrated and implantated with testosterone-filled silastic depots (in vitro release rate: 60 μg/24 h) prior to treatment with 10 mg cyproterone acetate (CyAc) on day 1, and 5 mg on days 4, 7, 10 and 13. Animals were sacrificed on day 14. Control animals were treated identically, with the exception of CyAc administration. Blood was collected and the ventral prostates of 6–8 animals were pooled, homogenized and processed into cytosol and purified nuclei. Steroid determinations (CyAc, testosterone, 5α-dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol (3α-diol)) were performed by RIA. Specifically bound DHT (charcoal resistant DHT = CR-DHT) represents DHT values (RIA) following treatment of cytosol or nuclear extract with dextran coated charcoal. The androgen receptor was determined in cytosol and nuclear extract by 'exchange assay' using [3H]methyltrienolone (MT) (18 h, 15°C).

The main results were: 1) The steroid levels in plasma (testosterone, DHT, 3α-diol) were in the range of untreated adult animals and not significantly influenced by the CyAc treatment. Final CyAc levels were 305 ± 58 nmol/l (mean ± sd, n = 5). 2) Significantly lower DHT, CR-DHT and testosterone levels (P at least < 0.01) were found in cytosol and in nuclei in the CyAc-treated group (cytosol (fmol/mg protein): DHT 305 ± 61 (n = 5), CR-DHT 54 ± 37 (n = 8), testosterone ≤ 8 (n = 5); nuclei (pmol/mg DNA): DHT 0.4 ± 0.2 (n = 5), CR-DHT 0.7 ± 0.2 (n = 3), testosterone ≤ 0.2 (n = 5)) when compared to controls (cytosol: DHT 645 ± 232 (n = 15), CR-DHT 204 ± 49 (n = 8), testosterone 24 ± 12 (n = 10); nuclei: DHT 5.0 ± 2.5 (n = 12), CR-DHT 3.1 ± 0.7 (n = 5), testosterone 0.9 ± 0.6 (n = 7)). 3α-diol was similar in the cytosol of both groups and could not be detected in the nuclei. 3) The androgen receptor concentration was increased in the cytosol of the CyAc-treated group (216 ± 17 (n = 4), control group 98 ± 10 (n = 5) fmol/mg protein, P < 0.001)) and decreased in the nuclear extract (0.61 ± 0.25 (n = 4), control 1.75 ± 0.25 (n = 5) pmol/mg DNA, P < 0.001). 4) The weight and DNA content of the prostate were reduced following CyAc treatment (weight 191 ± 11 mg (n = 9), DNA 622 ± 61 μg/organ (n = 8), controls 312 ± 9 (n = 8) and 838 ± 103 (n = 8), respectively).

The data demonstrate that an approximate 40-fold excess of CyAc over testosterone in plasma led to a distinct but partial reduction of nuclear DHT and androgen receptor values coinciding with partial effects on prostate weight and DNA content. These results reflect the ability of the prostate to maintain significant androgen stimulation in the presence of low nuclear DHT and androgen receptor values.
Distribution of neurotensin-like immunoreactivity in the hypothalamus, pituitary gland, and gastro-intestinal tract of rats
Authors: Muraki Koutarou , Okahata Hiroyasu , Nishi Yoshikazu , Usui Tomofusa , Yamada Hiroyasu , Fujita Susumu , Miyachi Yukitaka , Yanaihara Noboru , Yajima Haruaki
Published: December 2008

Abstract. The distribution of neurotensin-like immunoreactivity (NTLI) in the pituitary gland, hypothalamus, and throughout the gastro-intestinal tract of adult rats was determined by radioimmunoassay (RIA). NTLI concentrations were higher in the hypothalamus than in the pituitary gland or gastro-intestinal tract.

The anterior and posterior pituitary gland had almost the same concentration of NTLI. In the gastro-intestinal tract, the mucosal layer of the small intestine had abundant NTLI. The mucosal layer had higher NTLI levels than the muscular layer throughout the alimentary tract.