bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex steroids, adiposity and smoking in the pathogenesis of idiopathic hirsutism and polycystic ovary syndrome
Authors: Byrne Bridgette , Cunningham Sean , Igoe Derval , Conroy Ronan , McKenna T. Joseph
Published: June 2009

Hyperestronemia may be central to the development of polycystic ovary syndrome. The present study was designed to examine whether increased availability of androstenedione or increased aromatase closely associated with adiposity, plays the dominant role in the development of hyperestronemia. We measured plasma androstenedione, estrone and the estrone/androstenedione ratio (an indirect index of peripheral aromatase activity), in 141 patients with idiopathic hirsutism and in 88 patients with polycystic ovary syndrome. Estrone levels were higher in polycystic ovary syndrome, 250.4±129 (mean ± standard deviation) than in idiopathic hirsutism, 210.6±119 pmol/l, p<0.05. Plasma androstenedione levels were higher in polycystic ovary syndrome, 8.24±3.5, than in idiopathic hirsutism, 7.1±1.7 nmol/l, p<0.0025. However, the estrone/androstenedione ratio was similar in the two groups. In all patients who smoked, androstenedione was higher, 8.14±3.22 than in non-smokers, 6.99±2.96 nmol/l, p<0.005. Smokers had a lower body mass index, 23.9±2.3, than non-smokers 25.6±4.8 kg/m2, p<0.025. However, estrone levels were similar in smokers and in non-smokers. These data indicate that elevated estrone is more closely related to increased availability of androstenedione than to increased aromatase activity. While cigarette smoking appears to increase androstenedione levels, it may inhibit aromatase activity either directly or indirectly because of an associated reduction in adiposity. However, since the relative frequency of polycystic ovary syndrome and idiopathic hirsutism was similar in smokers and non-smokers, smoking did not appear to reduce estrone bioactivity as had been claimed.
Lymphocyte subset distribution and natural killer cell activity in men with idiopathic hypogonadotropic hypogonadism
Authors: Kiess Wieland , Liu Linda L. , Hall Nicholas R.
Published: June 2009

Sex-related differences in immune responsiveness are mediated at least in part by sex steroid hormones. Lymphocyte subset distribution in peripheral blood and natural killer cell function both have been reported to be under hormonal control. In order to gain more insight into sex steroid hormone action on the immune system, we have measured the lymphocyte subset distribution and natural killer cell activity in 18 men with idiopathic hypogonadotropic hypogonadism before treatment, and after hormonal treatment had normalized plasma testosterone levels. In untreated patients, the mean plasma testosterone concentrations were significantly lower than those in the treated men (3.0 ± 0.5 nmol/l vs 16 ± 1.7 nmol/l, p < 0.001). The percentage of peripheral CD3+ lymphocytes, CD8+ cells, the CD4+/CD8+ ratio, and the natural killer cell activity of peripheral mononuclear cells measured in a 51Cr release assay against target K 562 cells did not differ between patients with idiopathic hypogonadotropic hypogonadism and healthy adults, and most importantly, did not change during hormonal treatment which normalized plasma testosterone levels in the patients. In contrast, the percentage of peripheral CD4+ cells was significantly higher in untreated patients compared with normal adult subjects or patients with idiopathic hypogonadotropic hypogonadism after hormonal treatment that resulted in normal plasma testosterone levels (53 ± 2 vs 47 ± 2, p < 0.05). It should be noted that the percentage of peripheral CD 16+ cells was significantly lower in untreated men with low plasma testosterone levels than in normal controls. The percentage of CD16+ cells in peripheral venous blood rose significantly after hormonal treatment restored plasma testosterone levels to normal (6 ± 1 vs 11 ± 1, p < 0.001). In addition, the percentage of peripheral CD16+ cells correlated significantly with the plasma testosterone levels measured in men with idiopathic hypogonadotropic hypogonadism (r = 0.534, p < 0.001). In conclusion, both the percentage of peripheral CD4+ cells (T-helper lymphocytes) and peripheral CD16+ cells (non-T-non-B cells) are related to the plasma testosterone levels in men with idiopathic hypogonadotropic hypogonadism. These data suggest that in vivo human immune cells are under the regulatory influence of endogenous sex steroids.
The role of serum thyroglobulin concentration and thyroid ultrasound imaging in the detection of iodide transport defects in infants
Authors: Vulsma Thomas , Rammeloo Johan A. , Gons Margareth H. , de Vijlder Jan J. M.
Published: June 2009

When discovered by neonatal screening, a thyroid dyshormonogenesis is usually not recognized as a goitre. Especially a total iodide transport defect can easily be misclassified as thyroid agenesis, since radionuclide imaging cannot visualize the thyroid. We present the only iodide transport defect ever discovered in the Netherlands, the 35th reported in the literature, and the first one found exclusively as a result of neonatal screening. We demonstrate that iodide transport defects, in common with organification and deiodinase defects, can be distinguished from thyroid dysgenesis by demonstrating a normal or enlarged thyroid ultrasound image, and especially by measuring very high serum thyroglobulin levels (above 1000 pmol/l). In the presented case, an iodide-123 saliva-to-serum ratio near unity completed the etiologic classification. Measurement of serum thyroglobulin levels, in combination with thyroid ultrasound imaging, will improve the early identification of hereditary types of congenital hypothyroidism, and especially iodide transport defects, in patients found by neonatal thyroid screening.
Androstanediolglucuronide: A parameter for peripheral androgen activity before and during therapy with cyproterone acetate
Authors: Ponjee Gabriëlle A. E. , de Rooy Hans A. M. , Vader Huib L.
Published: June 2009

Serum 5α-androstane-3α,17β-diolglucuronide (3α-AdiolG) levels were measured and the degree of hirsutism was scored in female outpatients complaining of excessive hair growth before and during treatment with cyproterone acetate. In a group of 16 patients with idiopathic hirsutism and in a group of 9 patients with either polycystic ovary syndrome and hirsutism or 21-hydroxylase deficiency and hirsutism, the serum 3α-AdiolG levels were significantly increased (p<0.01) as compared with the serum 3α-AdiolG level in a control group of 13 apparently healthy women: 3α-AdiolG levels, median (range), being 5.3 (2.3-7.8) nmol/l, 8.5 (4.1-10.4) nmol/l, and 2.9 (1.5-5.2) nmol/l, respectively. In contrast to a previous report, no correlation was found between the serum 3α-AdiolG levels and the Quetelet Index (N=18, R=0.42, p>0.05), indicating an apparent ineffectiveness of the excessive androgen turnover in fat tissue. The use of the anti-androgen drug cyproterone acetate alone or in combination with ethinylestradiol in reverse sequential therapy did lower the 3α-AdiolG levels significantly (p<0.01) together with a significant decrease (p<0.01) in hirsutism score. From the results of this study we therefore conclude that 3α-AdiolG can be used as a parameter for peripheral androgen action before and during treatment with anti-androgens.
Production of corticosterone and testosterone in scorbutic mutant rats: difference of in vivo production between adrenal gland and testis
Authors: Fukuda Haruki , Ito Yasuhiro , Hirota Ryouji , Tsuji Motomu , Mori Hiroshi
Published: June 2009

Effects of deficiency in ascorbic acid on in vivo production of corticosterone and testosterone were examined using a mutant strain of rats unable to synthesize ascorbic acid. The adrenal weight of scorbutic rats was larger, and corticosterone levels in plasma and adrenal tissues were higher than those of ascorbic acid-supplied (ascorbutic) rats. Acute and chronic stimulation with ACTH increased corticosterone levels in both ascorbutic and scorbutic rats. In contrast, weights of seminal vesicles and ventral prostates in unstimulated scorbutic rats were smaller, and testosterone levels in plasma and testicular tissues were lower than those in ascorbutic rats. Acute stimulation with hCG increased testosterone levels only slightly in plasma and not in testicular tissues of scorbutic rats, when testosterone levels in ascorbutic rats reached a maximum. Chronic stimulation with hCG increased testosterone levels remarkably in both ascorbutic and scorbutic rats. These findings seem to indicate that ascorbic acid is not essential for the synthesis of steroid hormones. The scurvy seems to increase plasma ACTH levels secondary to the stress, resulting in the stimulation of the adrenals. In contrast, a prolonged deficiency in ascorbic acid appears to decrease plasma gonadotropin levels, and may reduce the sensitivity of testes to gonadotropins.
Receptors for insulin-like growth factor II in the rat uterus: characterization and variation throughout the estrus cycle
Authors: Chandrasekhar Yallampalli , Narayan Satya , Singh Pomila , Nagamani Manubai
Published: June 2009

This study was undertaken to identify uterine insulin-like growth factor II receptors and examine the regulation of these receptor levels throughout the estrus cycle. We have demonstrated IGF-II receptors in crude uterine membranes by binding and cross-linking experiments. IGF-II binding to the rat uterine membranes displayed time and temperature dependence and maximum binding was achieved by 2 h at 22°C. Uterine IGF-II binding sites were specific for binding IGF-II peptide and demonstrated negligible binding affinity for IGF-I and no affinity for insulin. The specific anti-IGF-II receptor antibody, R-II-PAB1, blocked the specific [125I]IGF-II binding to uterine membranes in a dose-dependent manner. The characteristics of uterine IGF-II receptor are similar to those reported for other tissues, with a single class of high-affinity binding sites with an apparent dissociation constant of 1.2±0.5 nmol/l and βmax of 2.65±0.41 pmol/mg protein. Affinity cross-linking experiments indicated that the specific binding of [125I]IGF-II in the uterus is associated with a single band of protein with a mol wt of 250 kD. In mature cycling rats, the proestrus uterus had the lowest level of [125I]IGF-II binding per mg membrane protein, without changes in receptor affinity. However, because of greater yield of protein from proestrus uteri, the total [125I]IGF-II binding capacity of the uterus was similar to the other stages of the estrus cycle. These studies demonstrate the presence of authentic IGF-II receptors in the rat uterus and illustrate variations in the concentration of these receptors in the uterus throughout the estrus cycle.
Participation of periventricular dopamine receptors in vasopressin secretion elicited by hypertonicity of systemic blood in rats
Authors: Yamaguchi Ken'ichi , Hama Hitoshi
Published: June 2009

The aim of this study was to examine in conscious rats the role of periventricular dopamine receptors in vasopressin secretion caused by hypertonicity of the systemic blood. Intracerebroventricular injections of dopamine (0.15 or 0.75 μmol) produced dose-related increases in plasma AVP 90 sec or 5 min later, without affecting plasma osmolality, concentrations of electrolytes, hematocrit, arterial pressure or heart rate. The AVP response to 0.75 μmol dopamine was blocked by its antagonists, SCH 23390, sulpiride and haloperidol, given intracerebroventricularly at a dose of 0.15 μmol 10 or 40 min before the injection of dopamine. The ip injections (2 ml/100 g) of 600 mmol/l NaCl produced, 15 or 30 min later, augmentations in plasma AVP accompanied by elevations in plasma osmolality, sodium and chloride. At a dose of 0.15 μmol given intracerebroventricularly 10 min before the injection of 600 mmol/l NaCl, SCH 23390 or sulpiride inhibited the AVP response at 15 min, and sulpiride or haloperidol inhibited that at 30 min. The increases in plasma osmolality and the electrolytes owing to hypertonic saline were not reduced by these dopamine antagonists. The intracerebroventricular applications of the antagonists followed by those of vehicles for dopamine or by ip injections of 150 mmol/l NaCl were without any effect on plasma AVP or the other plasma variables. On the basis of these results, we concluded that dopamine receptors in the periventricular regions may contribute to AVP secretion in response to hypertonicity of the systemic blood.
Repeated intraperitoneal injections of interleukin 1β induce glucose intolerance in normal rats
Authors: Wogensen Lise , Reimers Jesper , Mandrup-Poulsen Thomas , Nerup Jørn
Published: June 2009

Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1β on blood glucose and glucose tolerance in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 μg/kg of the mature form of recombinant IL-1β (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1β treated rats. An ip glucose tolerance test (0.2 g D-glucose/100 g) was performed 2 h after injection of rIL-1β. A single injection of rIL-1β caused a mild depression in blood glucose and an improved glucose tolerance. Multiple injections of rIL-1 β induced a diminished weight gain, a 24-28% reduction in food intake, a lasting mild depression of blood glucose (7 days) and a transiently impaired glucose tolerance on day 5. We conclude that systemic IL-1 should be considered an important regulator of glucose homeostasis in vivo.
Shrinkage of a primary thyrotropin-secreting pituitary adenoma treated with the long-acting somatostatin analogue octreotide (SMS 201-995)
Authors: Warnet André , Lajeunie Elisabeth , Gelbert Françoise , Duet Michèle , Chanson Philippe , Cophignon Jean , Harris Alan G.
Published: June 2009

The long-acting somatostatin agonist octreotide can control TSH hypersecretion from most thyrotropic adenomas. Octreotide therapy has even been shown to improve chiasmal dysfunction. We report another patient in whom octreotide therapy was associated with gradual suppression of TSH hypersecretion, which escaped partially, dramatic and very rapid and sustained improvement of chiasm compression, and dramatic and sustained shrinkage of an unresectable TSH-secreting pituitary tumour. Unusual and prolonged gastrointestinal adverse reactions eventually disappeared except for steatorrhea. In conclusion, octreotide may be considered as first line treatment in patients with unresectable thyrotropic adenomas.
Favourable response of a virilizing adrenocortical carcinoma to preoperative treatment with ketoconazole and postoperative chemotherapy
Authors: Kruimel Joanna W. , Smals Anthony G. , Beex Loek V. , Swinkels Leon M. , Pieters Gerlach F. , Kloppenborg Peter W.
Published: June 2009

A 25-year-old woman presented with an extensive adrenocortical carcinoma with severe virilization and mild Cushing's syndrome. In the tumour there was a primacy of the P450C17 (17,20-lyase) over the P450C21 (21-hydroxylase) route, favouring the synthesis of androgens over corticoids. Preoperatively, the patient was treated with the antimycotic agent ketoconazole, a known inhibitor of steroid synthesis, at a dose of 600 mg/day and after a week 1200 mg/day, to reduce operation risks and to achieve a better metabolic control. This treatment markedly decreased hyperandrogenism and normalized the hypercortisolism. The main effect of ketoconazole was at the 17,20-lyase level and probably at a locus prior in steroidogenesis, i.e. at the P450SCC and/or 17α-hydroxylase level. In contrast with other studies no effect at all was seen on the 11-hydroxylase activity of P450C11. After removal of a massive adrenal carcinoma, extending into the vena cava, vena cava resection and hemihepatectomy because of liver invasion, plasma cortisol and androgen values normalized. Despite adjuvant chemotherapy with o,p'-dichlor-diphenyl-dichloretan (4000 mg daily) hyperandrogenism soon recurred and lung metastases became manifest. Within 2 months after starting combined chemotherapy with 5-fluorouracil, cisplatin, and doxorubicin lung metastases almost completely disappeared with clinical and biochemical resolution of the hyperandrogenic state.
Effects of aging and sex on plasma insulin-like growth factor I (IGF-I) levels in normal adults
Authors: Yamamoto Hiroyuki , Sohmiya Motoi , Oka Nobuyuki , Kato Yuzuru
Published: June 2009

Effects of aging and sex on total plasma IGF-I levels were studied in 207 normal adults (103 males and 104 females), aged 21 to 80 years. Plasma IGF-I concentrations were measured by specific radioimmunoassay after extraction with acid-ethanol. Plasma IGF-I levels ranged from 50.8 to 480.6 μg/l with a mean (±sd) value of 200.7±81.9 μg/l in these normal adults. The mean plasma IGF-I levels were higher in females than in males in the second decade (332.6±63.9 vs 252.4±45.2 μg/l, p<0.01), whereas there was no sex difference in plasma IGF-I levels in elderly subjects. In both sexes, plasma IGF-I levels declined with age. In females, the slope of the regression line was much steeper in the young group (aged 21 to 40 years) than in the middle-aged and elderly group (aged 41 to 80 years) (y=−11.3x+641.7, r=−0.538, p<0.005 and y=−1.97x+289.3, r=−0.308, p<0.01). In males, plasma IGF-I linearly declined with age and the slope of the regression line (y=−2.36x+322.2, r=−0.480, p<0.005) was not considerably different from that of the middle-aged and elderly group in females.
Circadian, ultradian, and episodic gonadotropin and prolactin secretion in human pseudocyesis
Authors: Bray Mary A. , Muneyyirci-Delale Ozgul , Kofinas George D. , Reyes Francisco I.
Published: June 2009

Six women with pseudocyesis were studied by 15-min blood sampling for 12 to 24 h to determine their gonadotropin and PRL secretory profiles aiming to clarify the endocrine alterations in this form of hypothalamic amenorrhea. Clinical and biochemical evidence of hyperandrogenism was found in 4 patients. Persistent hyperprolactinemia was present only in one patient. Significant circadian and ultradian periodicities were identified by time series analysis in the 12-24 h profiles of FSH, LH and PRL secretion. Pulse analysis by the Van Cauter (UL-TRA.JN) method revealed a 24-h mean LH interpulse interval of 91±21 min with a mean LH amplitude of 5.4±0.8 IU/l. There was a significantly lower pulse frequency at night than during the daytime. The mean 24-h PRL interpulse interval and pulse amplitude were 134±22 min and 9.2±1.8 IU/l, respectively. Both FSH and LH mean levels were higher during the daytime than at night, while the reverse was true for PRL values. Decreased LH pulse frequeny and amplitude emerged as the most distinctive findings. Antecedent hypothalamic-pituitary aberrations due to other endocrinopathies and the timing of the hormonal assessment (e.g. recovery phase) may explain, at least in part, the reported heterogeneity of neuroendocrinologic findings in pseudocyesis.
The effect of insulin withdrawal on intermediary metabolism in patients with diabetes secondary to chronic pancreatitis
Authors: Larsen Steen , Hilsted Jannik , Philipsen Else K. , Tronier Bente , Nielsen Meta Damkjær , Worning Helge
Published: June 2009

Insulin was withdrawn from 7 patients with Type I (insulin-dependent) diabetes and 4 patients with insulin-dependent diabetes secondary to chronic pancreatitis, both groups without residual beta-cell function. Median plasma glucagon concentrations rose slightly, but significantly after withdrawal of insulin in Type I diabetic patients (from 14 (range: 11-16) to 19 (14-25) pmol/l by 6 h), but not in the patients with secondary diabetes. This was accompanied by a significantly higher increase in blood glucose concentration from 5.1 (4.9-5.7) to 15.2 (12.9-18.1) mmol/1 by 6 h in Type I diabetic patients compared with patients with secondary diabetes (from 4.9 (4.3-6.7) to 13.1 (10.9-13.5) mmol/l) (p<0.01). Beta-hydroxybutyrate increased to a similar extent in the two groups, whereas no significant increases were found in glycerol and lactate in any of the groups. Increased secretion of glucagon is not essential for the development of hyperglycemia and ketonemia in patients with diabetes secondary to chronic pancreatitis, but may augment the degree of hyperglycemia in Type I diabetic patients compared with patients having secondary diabetes.
Mitotane increases the blood levels of hormone-binding proteins
Authors: van Seters Arnoud P. , Moolenaar Abraham J.
Published: June 2009

In 3 patients with adrenocortical carcinoma the effects of long-term mitotane therapy on the serum levels of three hormone-binding globulins and vitamin D-binding protein were studied. Within the first month of treatment cortisol-binding globulin increased two to three times, in close correlation with sex hormone-binding globulin. The rises in thyroxine-binding globulin and vitamin D-binding protein were considerably less. Elevated cortisol-binding protein appeared to be associated with increased binding of cortisol, whereas the binding of thyroxine and vitamin D remained below normal. Binding proteins returned to normal in 2 patients within a year after mitotane discontinuation. This phenomenon of hormone-binding protein enhancement invalidates the use of total serum hormone levels to monitor the effects of mitotane on endocrine function and could provide an explanation for the increased cortisol substitution requirement during mitotane therapy.
Clinical evaluation of new assays for determination of serum calcitonin concentrations
Authors: Weissel M. , Kainz H. , Tyl Eva , Ogunyemi E. , Woloszczuk W.
Published: June 2009

In order to test the clinical usefulness of new commercially available kits for determination of calcitonin serum concentrations, we investigated the family (N=10) of a patient with medullary thyroid carcinoma and bilateral pheochromocytoma including his affected son, 10 athyreotic patients, totally thyroidectomized for non-medullary thyroid cancer, and 4 normal volunteers. Pentagastrin tests were performed in all subjects. Serum calcitonin levels before and after pentagastrin were determined by 4 kits. Kits A and B are immunoradiometric assays of the sandwich-type, kits C and D are radioimmunoassays, D being the one hitherto routinely used. Our results show that the new assays (kits A, B and C) have a better diagnostic accuracy in screening for medullary thyroid cancer than the RIA (kit D), hitherto used, where basal values overlapped with normals. Although basal values of normals were mostly near the detection limit of all 4 kits, kits A and B were sensitive enough to detect stimulation of calcitonin secretion by pentagastrin in all subjects with intact thyroid glands and kit C in most of them. The lack of increase in calcitonin after pentagastrin observed by kits A, B and C in athyreotic patients suggests deficiency of secretion of this hormone. Only kit D was unable to show this deficiency.
Evidence for dopamine-related and TRH-related pituitary TSH and PRL pools in patients with prolactinoma
Authors: Hanew Kunihiko , Utsumi Atsushi , Sugawara Akira , Shimizu Yasuyuki , Yoshinaga Kaoru
Published: June 2009

The sources of TSH, which was excessively released by sulpiride (dopamine D2 receptor antagonist), were studied in 15 female patients with PRL-secreting adenoma (18-43 years). Sequential 3-day administration of sulpiride (100 mg, im) was given to 12 patients with prolactinoma and 6 normal female subjects (19-24 years). Patients with prolactinoma showed much greater TSH responses than normal subjects on the first day. However, TSH responses to sulpiride disappeared on the 2nd and 3rd day in both groups. In contrast, plasma PRL responses to the 1st sulpiride administration were smaller in patients with prolactinoma than in normal subjects, and the response disappeared following the 2nd administration in both groups. When TRH (500 μg, iv) was administered 120 min after the 3rd sulpiride injection, TSH and PRL increments were not different from those before the sulpiride injection in both patients with prolactinoma (N=6) and normal subjects (N=6) Further, combined administration of sulpiride and TRH in 5 patients with prolactinoma clearly enhanced the TSH and PRL responses compared with the single administration of each agent. These results suggest that there may be two readily releasable pituitary TSH and PRL pools, i.e. one dopamine-related and the other TRH-related, in patients with prolactinoma and normal female subjects.
Intracerebral administration of insulin-like growth factor I decreases circulating growth hormone levels in the fetal pig
Authors: Spencer G. S. G. , Macdonald A. A. , Buttle H. L. , Moore L. G. , Carlyle S. S.
Published: June 2009

Radioimmunoassayable IGF-I levels were measured in the cerebrospinal fluid and plasma of pig fetuses at 94 days gestational age. Mean plasma IGF-I levels were 128.5 ± 5.8 μg/l while the concentration in the cerebrospinal fluid was 25.8 ± 4.4 μg/l. The effect of intracerebroventricular administration of IGF-I on circulating GH levels was also studied in pig fetuses in utero. Eighteen pig fetuses were fitted with indwelling carotid artery and juglar vein catheters. Nine fetuses were given 1500 ng of pure IGF-I in 100 μl 0.9% saline by direct injection into a right lateral ventricle. Nine further fetuses (controls) were similarly given 100 μl of saline without IGF-I. GH levels in the control fetuses were ~200 μg/l and showed marked fluctuations with episodic intervals of about 40 min. By contrast, in the IGF-I-treated fetuses, GH levels were dramatically lowered by 20 min after IGF administration and remained low throughout the 4-h study. The episodic variations in GH were abolished and levels remained fairly constant at ca. 40 μg/l. From these results we surmise that the low levels of IGF-I in the fetus may contribute to their high GH levels. At this stage it is not possible to identify whether the IGF-I inhibition is a direct effect on the pituitary or is mediated by increased somatostatin, decreased GHRH or both.
Triiodothyronine and insulin effects on malic enzyme in hypothyroid and diabetic rats
Authors: Ortiz-Caro Javier , Jolin Trinidad
Published: June 2009

We examined the effects of T3 and insulin on the activity of hepatic mitochondrial α-glycerophosphate dehydrogenase and cytosolic malic enzyme in control, thyroidectomized, thyroidectomized food-restricted, and thyroidectomized diabetic rats. In the three untreated thyroidectomized groups, the decrease in hepatic nuclear T3 content was accompanied by a marked reduction in the levels of α-glycerophosphate dehydrogenase and malic enzyme activity. Although the levels of both enzymes were increased by a receptor-saturating dose of T3, the α-glycerophosphate dehydrogenase response in the thyroidectomized groups was almost identical to that in controls, whereas that of malic enzyme was reduced to 45-62% of control values. Insulin failed to stimulate the α-glycerophosphate dehydrogenase levels in untreated and T3-treated thyroidectomized groups, but caused an increase in malic enzyme activity by 79-130% in untreated thyroidectomized groups, and enhanced the activity of this enzyme to about twice that seen with T3 alone. These effects were independent of changes in nuclear T3 binding parameters. The data suggest that insulin may act on malic enzyme synthesis through its general stimulatory effect on protein synthesis, or by antagonizing factors that inhibit the induction of this enzyme.
Influence of interleukin 6 on the function of secondary cultures of human thyrocytes
Authors: Rasmussen Å. Krogh , Kayser L. , Bech K. , Feldt-Rasmussen U. , Perrild H. , Bendtzen K.
Published: June 2009

Interleukin 6 has been suggested as second mediator of the effects of interleukin 1 in some cell systems. Interleukin 1 has previously been shown to inhibit the function of human thyrocytes in secondary cultures. We have therefore studied the influence of interleukin 6 (10−1−5·107 U/l) on the function of thyroid cells. Recombinant interleukin 6 slightly inhibited the production of cAMP, but failed to influence the production of thyroglobulin or the DNA content. Endotoxins (lipopolysaccharides from Salmonella abortus equi or Yersinia enterocolitica) had only a slightly inhibitory effect on thyroid cell functions, and the effect of interleukin 6 could not by itself be explained by endotoxin contamination. The effect of interleukin 6 did not mimick effects on thyroid cells afforded by recombinant interleukin 1α and 1β. Furthermore, antibodies to interleukin 6 were not able to inhibit the interleukin 1β-induced inhibition of thyroid cell functions. In conclusion, it is unlikely that interleukin 6 by itself mediates the biological effects of interleukin 1 on human thyroid cells.
Osmoregulation of systemic vasopressin release during long-term glucocorticoid excess: A study in dogs with hyperadrenocorticism
Authors: Biewenga Wim J. , Rijnberk Ad , Mol Jan A.
Published: June 2009

In 9 dogs with pituitary-dependent hyperadrenocorticism and in 6 dogs with hyperfunctioning adrenocortical tumours, the osmoregulation of arginine vasopressin (AVP) release was investigated by iv infusion of 20% NaCl for 2 h at a rate of 0.03 ml per kg body weight. The responses were analysed in terms of sensitivity and threshold of the osmoregulation of AVP secretion. The sensitivity was normal in 6 dogs and lowered in 9. In 4 of the latter dogs there was complete absence of a response to hypertonicity. The osmotic threshold of AVP release was raised in 9 dogs and normal in 2 dogs, whereas in the four dogs without any response the term threshold was not applicable. The results were not different for dogs with pituitary-dependent hyperadrenocorticism and dogs with hyperfunctioning adrenocortical tumour. It is concluded that corticosteroid excess per se induces a marked impairment of the osmoregulation of AVP secretion. The loss of reactivity of the osmoreceptor system may contribute to the corticosteroid-induced polyuria, which is also the result of resistance to AVP in the kidney.
Enhancement by growth hormone of phorbol diester-stimulated respiratory burst in human polymorphonuclear leukocytes
Authors: Spadoni Gian Luigi , Spagnoli Anna , Cianfarani Stefano , Del Principe Domenico , Menichelli Adriana , Di Giulio Stefano , Boscherini Brunetto
Published: June 2009

The oxidative metabolic burst of mononuclear and polymorphonuclear phagocytes can be stimulated to produce free oxygen radicals. Several substances can enhance this respiratory burst activity by a priming action: recently growth hormone (rat and porcine) was demonstrated to act as a priming agent on rat peritoneal and on porcine alveolar macrophages. In our study we wanted to verify whether also human GH had a similar priming action on homologous cells, in particular on polymorphonuclear leukocytes. To determine the oxidative activity of polymorphonuclear leukocytes, after stimulation with phorbol myristate acetate, a flow-cytometric assay was employed which registered the intracellular formation of highly fluorescent products as indicators for the intracellular formation of hydrogen peroxide. The incubation of phorbol myristate acetate-stimulated polymorphonuclear leukocytes with GH resulted in a time-dependent and dose-dependent increase in fluorescence, thus demonstrating that human GH enhances in vitro the oxidative metabolic burst of these cells. The action of GH appeared to be significant after 30 min of incubation, was maximal at 60 min, and decreased after 90 min. After one hour of incubation, the first significant variation of fluorescence appeared with GH at a concentration of 50 μg/l. The maximum effect was seen at 100 μg/l with no further increase. Specificity of GH action was demonstrated by the inhibition of its effect by the addition of monoclonal antibodies to GH.
Effect of diabetes mellitus on levels of atrial natriuretic hormone in plasma and the right atrium in the non-obese diabetic mouse
Authors: Yano Shuichi , Tanigawa Keiichiro , Suzuki Shusaku , Kobayashi Yuta , Shimada Toshio , Morioka Shigefumi , Kato Yuzuru , Moriyama Katsutoshi
Published: June 2009

Atrial natriuretic hormone (ANH) levels in plasma and the right atrium of non-bose diabetic mice in the decompensated diabetic state were investigated by radioimmunoassay and histological examination. Severely diabetic mice, with blood glucose levels over 33.6 mmol/l showed significantly higher hematocrit, plasma sodium and calculated plasma osmolarity than the age-matched normoglycemic mice. The plasma ANH levels in diabetic mice were significantly lower (17.5 pmol/l than those in normoglycemic mice (43.6 pmol/l). The ANH concentrations in the right atrium were 26.6 mg/g protein in the diabetic and 11.2 mg/g protein in the normoglycemic mice. The right atrium in the diabetic mice showed much wider immunohistochemical staining by anti-human ANH antiserum compared with the normoglycemic mice. An increase in the number of atrial specific granules in the diabetic mice was observed by transmission and scanning electron microscopy. Morphometrical analysis indicated that the number of granules increased to more than twice that in the normoglycemic mice. These findings indicate that plasma ANH decreases in diabetic mice. The store of right atrial ANH may be increased to compensate for the marked dehydration in severe diabetes.
The role of histamine in the neuroendocrine regulation of pituitary hormone secretion
Authors: Knigge Ulrich , Warberg Jørgen
Published: June 2009

The neurotransmitter histamine participates in the neuroendocrine regulation of pituitary hormone secretion by an indirect action at a hypothalamic level where histaminergic neurons are abundant. The effect of histamine is caused by activation of postsynaptic H1- or H2-receptors. Histamine stimulates the secretion of ACTH, β-endorphin (mediated by CRH and AVP), α-MSH (mediated by dopamine and peripheral catecholamines), and PRL (mediated by dopamine, serotonin and AVP), and participates in the stress-induced release of these hormones and possibly in the suckling- and estrogen-induced PRL release. The release of GH and TSH is predominantly inhibited by histamine; however, uncertainty exists regarding its role and the hypothalamic factors involved. Histamine increases the secretion of LH in females (mediated by GnRH), and may be involved in the mediation of the estrogen-induced LH surge. AVP and oxytocin are stimulated by histamine, probably by an effect in the supraoptic and paraventricular nuclei of the hypothalamus.
Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: Improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand
Authors: Bang Peter , Eriksson Ulla , Sara Vicki , Wivall Inga-Lena , Hall Kerstin
Published: June 2009

Insulin-like growth factor binding proteins interfere in the IGF-I and -II radioimmunoassays. In an attempt to overcome this problem, we have compared the use of truncated IGF-I, with reduced IGFBP affinity, and IGF-I as radioligands for IGF-I RIA measurements in serum separated by acid gel filtration or acid ethanol extraction followed by cryo-precipitation. With truncated IGF-I as radioligand the IGF-I measurements in acid gel filtrates and acid ethanol extracts were significantly correlated in healthy subjects (N=42, r=0.91, p<0.001) and in patients with acromegaly (N=10, r=0.85, p<0.01), GH deficiency (N=10, r=0.88, p<0.001) or Type I diabetes mellitus (N=10, r=0.90, p<0.001). In contrast, the IGF-I concentrations in acid ethanol extracts determined with IGF-I as radioligand did not correlate with those in acid gel filtrates using truncated IGF-I radioligand in patients with acromegaly (r=0.61, NS) or GH deficiency (r=0.46, NS). In the latter group the mean IGF-I concentrations measured in acid ethanol extracts were erroneously elevated by 112%. Low-affinity antibodies used for IGF-II RIA determinations failed to give reliable results in acid ethanol extracts from patients with Type I diabetes mellitus or GH deficiency. In conclusion, erroneously high IGF-I concentrations owing to binding of the radioligand to IGFBPs not completely removed by acid ethanol extraction can be avoided by the use of truncated IGF-I as radioligand.
Predominant intraepithelial localization of primed T cells and immunoglobulin-producing lymphocytes in Graves' disease
Authors: Paschke R. , Brückner N. , Schmeidl R. , Pfiester P. , Usadel K. H.
Published: June 2009

It has been proposed that intrathyroidal lymphocytes, localized in specific anatomical sites might have distinct, pathophysiologically relevant functions in Graves' disease. However, most studies of intrathyroidal lymphocytes were restricted to two lymphocyte locations and used semiquantitative methods. Therefore we used seven anatomically different lymphoid compartments to classify and evaluate by quantitative representative methods the total intrathyroidal lymphocytic infiltration and the staining indexes for immunoglobulin-producing plasmocytes and primed T cells (CD45RO), which provide maximum help to pokeweed mitogen-stimulated immunoglobulin synthesis in 36 thyroid glands from patients with Graves' disease. We found only 3.4% of all intrathyroidal lymphocytes intraepithelially. However, only intraepithelial lymphocytes showed a significantly higher staining index for primed T cells compared with several other compartments. There was also a high staining index for immunoglobulin-producing lymphocytes in this compartment. Kappa- and lambda-positive plasmocytes were found in a polyclonal distribution (kappa:lambda=64.1: 35.9) in all compartments. This increased incidence of CD45RO-positive T lymphocytes and of immunoglobulin-producing lymphocytes among the intraepithelial lymphocytes suggests a distinct pathophysiological function of lymphocytes in peripolesis in Graves' disease. Furthermore, there is a polyclonal intrathyroidal immunoglobulin synthesis.
Insulin resistance, but normal basal rates of glucose production in patients with newly diagnosed mild diabetes mellitus
Authors: Hother-Nielsen Ole , Beck-Nielsen Henning
Published: June 2009

Fasting hyperglycemia in Type II (non-insulin-dependent) diabetes has been suggested to be due to hepatic overproduction of glucose and reduced glucose clearance. We studied 22 patients (10 lean and 12 obese) with newly diagnosed mild diabetes mellitus (fasting plasma glucose <15 mmol/l, urine ketone bodies <1 mmol/l), and two age- and weight-matched groups of non-diabetic control subjects. Glucose turnover rates and sensitivity to insulin were determined using adjusted primed-continuous [3-3H]glucose infusion and the hyperinsulinemic euglycemic clamp technique. Insulin-stimulated glucose utilization was reduced in both diabetic groups (lean patients: 313±35 vs 531±22 mg·m−2·min−1, p<0.01;obesepatients:311±28vs453±26mg·m−2·min−1, p<0.01). Basal plasma glucose concentrations decreased 0.43±0.05 mmol/l per h (p<0.01). Glucose production rates were smaller than glucose utilization rates (lean patients: 87±3 vs 94±3 mg·m−2·min−1, p<0.01; obese patients: 79±5 vs 88±5 mg·m−2 ·min−1, p<0.01), were not correlated to basal glucose or insulin concentrations, and were not different from normal (lean controls: 87±4 mg·−2·min−1; obese controls: 80±5 mg·m−2·min−1). These results suggest that the basal state in the diabetic patients is a compensated condition where glucose turnover rates are maintained near normal despite defects in insulin sensitivity.
Sleep deprivation reduces LH secretion in men independently of melatonin
Authors: Strassman RickJ. , Qualls Clifford R. , Lisansky E.Jonathan , Peake Glenn T.
Published: June 2009

Melatonin affects gonadal function in nonprimate mammals. Confirmatory data in man are not available. We assessed melatonin's acute effects on luteinizing hormone secretion in 17 normal men. We studied these men in conditions of sleep in the dark, and sleep deprivation in bright light, dim light, and bright light combined with a physiologically relevant infusion of melatonin, while measuring blood levels of immunoreactive LH every 20 min for 7 h. We compared overnight LH secretion, and LH pulse frequency, amplitude, length, interval and area under the curve using a modification of the PULSAR peak identification program, among the four treatments. Areas under the curve for peaks in all three conditions of sleep deprivation were lower than in normal sleep. The presence or absence of melatonin had no additional effect. We conclude that acute suppression of melatonin does not affect LH pulse parameters in normal man, but that sleep deprivation may reduce the amount of LH secreted per pulse.
Evidence for acute release of thyroid peroxidase during subtotal thyroidectomy
Authors: Feldt-Rasmussen U. , Høier-Madsen M. , Date J. , Blichert-Toft M.
Published: June 2009

An immediate reduction of thyroglobulin autoantibodies during subtotal thyroidectomy of thyroglobulin antibody positive patients has previously been shown to indicate an acute release of thyroglobulin into the circulation peroperatively. The aim of the present study was to investigate whether thyroid peroxidase was also released by measuring anti-thyroid peroxidase antibodies by a quantitative and antigen specific method both per- and postoperatively in patients positive for anti-thyroid peroxidase antibodies. Twelve anti-thyroid peroxidase positive patients (11 females, 1 male) referred for surgery of toxic goitre were studied. Median age was 43 years (range 24-64) and median goitre size 86 g (25-165). All patients had been pretreated with antithyroid drugs and were euthyroid at the time of operation. Anti-thyroid peroxidase was measured before operation, 1-8 h, 10 days, 1-3 months, and 12 months postoperatively by a commercial method (DYNO-test®, Henning, Berlin). The median anti-thyroid peroxidase level before operation was 1048 kU/l (range 68-10 517 kU/l) and fell during operation to 0.63 (range 0.37-1.28) (p<0.01) of initial concentration without further decrease during the next 1-8 h. The comparative decrease in thyroglobulin antibodies was 0.19 (0-0.88). The anti-thyroid peroxidase level was increasing after 10 days, but did not reach initial level until between 3 and 12 months after surgery. However, in 3 of 10 patients anti-thyroid peroxidase had disappeared after 12 months, all of whom had low levels before operation, whereas anti-thyroid peroxidase was 2-4 times higher than preoperatively in 3 other patients. The present study thus gives evidence for an acute release of thyroid peroxidase into the circulation during thyroid surgery able to decrease anti-thyroid peroxidase activity almost to the same degree as the Tg-induced decrease in Tg-ab.
Inhibitory effects of gossypol on adrenal function
Authors: Wu Yan-Wan , Chik Constance L. , Albertson Barry D. , Linehan W. Marston , Knazek Richard A.
Published: June 2009

Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3β-hydroxysteroid dehydrogenase Δ5-Δ4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.
Differentiation-dependent expression of calcitriol actions on absorptive processes in cultured chick intestine: modulation by triiodothyronine
Authors: Cross Heide S. , Peterlik Meinrad
Published: June 2009

Embryonic chick jejunum maintained in organ-culture exhibits a characteristic stage-specific pattern of responses to calcitriol and T3. Whereas induction of luminal Na+/inorganic phosphate and Na+/D-glucose transport by calcitriol was only possible at an advanced state of differentiation prior to hatching on day 20, the sterol induced cellular calcium transport with high efficiency even in undifferentiated enterocytes in day 15 embryonic intestine. T3 had no effect at all on calcium transport, but induced Na+/inorganic phosphate transport at all stages of epithelial maturation. In contrast, Na+/D-glucose transport was effectively induced by T3 only in relatively immature intestinal epithelium. T3, at a medium concentration of 10−8 mol/l, in a permissive fashion potentiated the effects of calcitriol (10−10−10−7 mol/l) on calcium transport as well as on Na+/inorganic phosphate and Na+/D-glucose transfer. Thereby, T3 facilitated induction of transport activities by calcitriol against differentiation-related restraints. By facilitating the expression of genomic actions of calcitriol, T3 may thus play an important role in the regulation of calcium and phosphate metabolism.
The α-galactosyl epitope on mammalian thyroid cells
Authors: Thall Aron , Etienne-Decerf Jacqueline , Winand Roger J. , Galili Uri
Published: June 2009

Studies on the distribution of α-galactosyl epitopes with the structure Galα1→3Galβ1→4GlcNac-R on mammalian thyroid cell membranes are of interest, since a natural antibody interacting with this carbohydrate antigen (i.e. the natural anti α-galactosyl IgG antibody) was found to increase in its titre in patients with autoimmune thyroid disorders. By using a radioimmunoassay for quantification of the α-galactosyl epitope, we found variable concentrations of this epitope on thyroid cell membranes of all nonprimate mammals and New World monkeys studied, but not in Old World monkeys and human thyroid. The absence of the identifiable α-galactosyl epitopes on human and Old World monkey thyroid cells correlates with diminished activity of the enzyme, α1-3 galactosyltransferase, which, in other species, synthesizes the α-galactosyl epitopes within the Golgi apparatus. It is argued that a proportion of anti-thyroid reactivity in human normal and pathologic sera, when assayed with mammalian thyroid cells, may be attributed to natural anti α-galactosyl IgG antibody, which interacts with α-galactosyl epitopes on thyroid tissues used for the bioassay.