bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin stimulation of somatomedin A production in monolayer cultures of rat hepatocytes
Authors: Kogawa Megumi , Takano Kazue , Asakawa Kumiko , Hizuka Naomi , Tsushima Toshio , Shizume Kazuo
Published: December 2008

Abstract. The effect of insulin on the generation of somatomedin by a monolayer culture of rat hepatocytes was investigated. Release of somatomedin into the medium of cultured hepatocytes was observed for at least three days, as determined by a radioreceptor assay for somatomedin A. The addition of 1–100 μg/ml insulin to the medium caused dose-related increases in somatomedin A in the conditioned medium for up to three days. The conditioned medium also stimulated DNA synthesis in human fibroblasts.

To investigate hormone degradation by hepatocytes, labelled somatomedin A or insulin was added to the medium and the degradation was examined by trichloroacetic acid (TCA) precipitation, and gel chromatography. Although [125I]somatomedin A was slightly degraded even after 24 h of incubation, [125I]insulin was degraded within 6 h and the TCA precipitation at 24 h was 15% only. This degradation of hormones was inhibited by 1 mm bacitracin. Insulin stimulation of somatomedin production was significantly increased to 131.2% as compared with cultures without bacitracin.

The molecular size of the somatomedin released into the medium was greater than that of purified somatomedin, suggesting that this somatomedin is bound to carrier proteins.
Studies on the mechanism of acute glucose-induced aldosterone suppression. Role of corticotrophin
Authors: Ferrier Claudia P. , Bianchetti Mario G. , Beretta-Piccoli Carlo , Link Ladislav , Bachman Claude , Weidmann Peter
Published: December 2008

Abstract. A possible role of corticotrophin in mediating the acute glucose-induced suppression of plasma aldosterone was assessed in two groups of normal subjects (group A, N = 9 and group B, N = 10), by studying the effects of a standard oral glucose loading test on plasma concentrations of glucose, insulin, cortisol, potassium, aldosterone and renin activity, a) under basal conditions (groups A and B), b) after 2 days of dexamethasone (0.5 mg/6 h) (group A), c) after 8 weeks of treatment with the diuretic indapamide, 2.5 mg/day (group B) and d) after additional 2 days of combined administration of indapamide and dexamethasone (0.5 mg/6 h) (group B). In addition, the spontaneous daytime related variations of these parameters were assessed in group A in a control study without glucose loading. Under basal conditions, the acute increase in plasma glucose and insulin was accompanied by a significant decrease of plasma potassium (P < 0.01), cortisol (P < 0.01) and by a slight increase in plasma renin activity. None of these changes occurred in the control experiment without glucose loading. Dexamethasone caused a significant decrease in pre-loading plasma aldosterone. Indapamide caused a significant decrease in pre-loading plasma potassium and a marked stimulation of renin and aldosterone. After combined indapamide-dexamethasone administration, pre-loading plasma aldosterone decreased to control values. Glucose loading under dexamethasone or combined indapamide-dexamethasone administration caused a similar suppression of plasma aldosterone as observed under control conditions.

These findings suggest that corticotrophin does not play an important role in mediating the acute aldosterone inhibitory effect of glucose loading. However, corticotrophin may contribute to the maintenance of the secondary hyperaldosteronism induced by diuretic treatment.
Changes in gonadotrophin binding to rat ovaries during sexual maturation
Authors: Uilenbroek J. Th. J. , van der Linden R.
Published: December 2008

Changes in LH and FSH binding to rat ovaries during sexual maturation were measured by in vitro binding assay and autoradiography. Ovaries were obtained from rats at various ages ranging from 5 till 35 days of age. Animals older than 35 days of age were classified in three groups: anoestrus (uterine weight below 60 mg), early pro-oestrus (uterine weight 60–120 mg) and pro-oestrus (uterus distended with fluid). Measurements were made of specific binding of radioiodinated hCG and rFSH to ovarian homogenates (day 5–35) and to granulosa cells isolated from the largest follicles (day 35–pro-oestrus).

The earliest age at which specific hCG and FSH binding could be demonstrated was day 11. Thereafter hCG binding to ovarian homogenates, expressed in cpm/μg DNA, increased with age. Specific binding of hCG to granulosa cells increased from 1000 cpm/μg DNA at day 35 to 4000 cpm/μg DNA at pro-oestrus. FSH binding to ovarian homogenates increased till day 21 and remained fairly constant thereafter.

Autoradiography revealed the presence of hCG binding to interstitial tissue and thecal cells. hCG binding to granulosa cells was only found in large pre-ovulatory follicles present at early pro-oestrus and pro-oestrus. FSH binding was observed to granulosa cells of all types of follicles, but not to interstitial and thecal cells.

The results demonstrate that during sexual maturation FSH binding to granulosa cells remains constant, whereas LH binding to interstitium and theca and ultimately to granulosa cells increases with age suggesting an increased responsiveness of the ovaries to LH.
Treatment of hyperprolactinaemic patients with pergolide
Authors: L'Hermite Marc , Debusschere Pierre M. , Gillet Clémentine , Deschepper Christian
Published: December 2008

Abstract. Eighteen hyperprolactinaemic patients were orally treated for up to 16 months with pergolide mesylate, a new potent long-lasting dopaminergic ergot derivative. In all cases, Prl normalization (< 25 ng/ml) was achieved at a once-a-day dose of 50–300 μg. All women recovered and/or exhibited normal menstrual function. Among the 6 women wishing to become pregnant, 4 of them conceived within 4 months; there were other causes for infertility than hyperprolactinaemia in the 2 other couples.

A macroprolactinoma man experienced important improvement in well-being as well as objective regression of his visual fields defect. This suggests a shrinkage effect of pergolide on the tumoural process. Another man regained normal potency and normal testosterone within 2 weeks.

While 10 patients were completely free of any side effect, 7 experienced transiently mild gastro-intestinal side effects or postural hypotension. Only one patient discontinued her treatment because of dizziness.

The present study demonstrates the high potency, the good tolerance and the excellent efficacy of pergolide in the treatment og hyperprolactinaemia.
GABA-ergic and dopaminergic mechanisms in gonadotrophin secretion in males – effects of baclofen and metoclopramide
Authors: Elias Alan N. , Szekeres Agnes V. , Stone Sergio , Valenta Lubomir J. , Haw Tarek , Ascher Michael S.
Published: December 2008

Abstract. The GABA analogue, baclofen, and the dopamine antagonist, metoclopramide, were studied with respect to their effects on basal and LRH-induced LH and FSH release in 6 normal male volunteers. Basal gonadotrophin secretion was unchanged following the administration of baclofen or metoclopramide given alone or in combination. LRH-stimulated LH release was significantly blunted after metoclopramide administration in the baclofen pre-treated volunteers. Serum LH concentration (mean ± sd) in the control phase was 30.1 ± 17.2 mIU/ml and was 19.4 ± 9.6 mIU/ml after baclofen plus metoclopramide (P < 0.02). LRH-stimulated values, however, were unaffected by baclofen or metoclopramide when the drugs were given alone. LRH-stimulated FSH release was not significantly influenced by baclofen or metoclopramide given alone or in combination. Basal Prl secretion increased significantly when baclofen and metoclopramide were given separately and in combination. Basal Prl concentration (mean ± sd) increased from 14 ± 2 ng/ml to 18.7 ± 4.8 ng/ml after baclofen and to 111.5 ± 31.9 ng/ml after metoclopramide (P<0.01). The rise in serum Prl concentration, however, was not significantly different when measured after metoclopramide alone (111 ± 31.9 ng/ml) or after metoclopramide and baclofen (112 ± 33.3 ng/ml). It is proposed that GABA and dopamine exert opposing effects on LH secretion in normal men.
No acute effect of pimozide on the plasma GH levels in acromegaly
Authors: Nortier J. W. R. , Croughs R. J. M. , Donker G. H. , Thijssen J. H. H. , Schwarz F.
Published: December 2008

Abstract. In 34 acromegalic patients either untreated or inadequately treated by surgery and/or radiotherapy the plasma GH levels and plasma Prl levels were determined during 8 h after the acute administration of the dopamine agonist bromocriptine and during 150 min after the administration of the dopamine antagonist pimozide.

A 50% or more suppression of the basal GH levels was arbitrarily defined as a positive response. Seventeen patients displayed a positive response to bromocriptine, 17 patients displayed a negative response to bromocriptine. Plasma Prl levels were elevated in 6 of 17 bromocriptine responders and in 2 of 17 bromocriptine nonresponders. There was no difference in the plasma GH response to pimozide administration in the patients with a positive or a negative GH response to bromocriptine.

With one exception there was in no patient a positive GH response to pimozide. In further experiments the plasma GH response to pimozide was measured during 11 h in 6 bromocriptine sensitive and 6 bromocriptine insensitive patients. Again no difference was found between bromocriptine responders and non-responders. There was also no difference in the Prl response to bromocriptine or pimozide between GH responders and GH non-responders. The Prl response to pimozide was blunted in comparison to a control group.

The present study does not lend support to the idea that there is a fundamental difference in the degree of hypothalamic dopaminergic control of GH or Prl secretion between bromocriptine sensitive and bromocriptine insensitive patients with acromegaly.
Suppression of electroacupuncture(EA)-induced β-endorphin and ACTH release by hydrocortisone in man. Absence of effects on EA-induced anaesthesia
Authors: Masala A. , Satta G. , Alagna S. , Zolo T. A. , Rovasio P. P. , Rassu S.
Published: December 2008

Abstract. Auricular electroacupuncture (EA) increased plasma ACTH and β-endorphin levels significantly in 10 patients receiving EA as an analgesic aid during surgery. Pre-treatment with iv hydrocortisone (200 mg) completely suppressed both ACTH and β-endorphin release in response to EA without significantly affecting EA anaesthesia in 6 other patients and in a patient with Addison's disease.
Metabolic actions of pituitary growth hormone
Authors: Bornstein J. , Ng F. M. , Heng D. , Wong K. P.
Published: December 2008

Abstract. Evidence is presented showing that human growth hormone (hGH) and its part sequence hGH 172–191 inhibit acetyl CoA carboxylase and hence fatty acid synthesis by interacting with adipocyte and hepatocyte plasma membranes, resulting in the release of a relatively non-polar second 'mesenger'. This second 'messenger' inhibits the enzyme in a soluble fraction by increasing its phosphorylation. It appears that growth hormone requires some modification prior to demonstrating this activity, as it is active in intact cells and unfractionated homogenates but has no activity in 'messenger release' from purified membrane fractions. The relations of these actions to the in vivo effects of hGH are discussed.
Computerized cranial tomography in the evaluation of pituitary tumours in rats
Authors: Casanueva Felipe F. , Gordon William L. , Friesen Henry G.
Published: December 2008

Abstract. The use of the rat as an animal model in studies of pituitary tumours has been hampered by the great individual variation and the necessity of killing the animal to assess the development and progression of tumour growth. A study was designed to determine whether computed tomography (CT) could be used to monitor the growth of pituitary tumours in female Sprague-Dawley rats. Animals were injected with oestradiol valerate 2 mg/3 weeks sc, an amount known to lead to development of pituitary tumours (from 45 to 378 mg pituitary weight). Control rats were treated with vehicle alone.

Anaesthetized rats injected with contrast were studied by computerized axial tomography and the single CT scans (coronal cuts) were correlated with direct anatomical measurements obtained after pituitary dissection. All pituitaries weighing more than 54 mg were detected by the CT scanner. A good correlation between measurements made after anatomical dissection was found in the two main axes of the coronal cuts.

In conclusion, CT scanning can be used for assessment of pituitary tumour size in the rat. This technique should be especially helpful in studies where individual evaluation and/or repeated measurements over time are necessary.
Arginine vasopressin suppresses oxytocin release from the superfused rat hypothalamo-pituitary complex
Authors: Miyake A. , Tasaka K. , Sakumoto T. , Aono T.
Published: December 2008

Abstract. The role of arginine vasopressin (AVP) in the regulation of oxytocin secretion was studied in a superfusion system of the hypothalamo-pituitary complex from cycling female rats in dioestrus of the oestrous cycle. After perfusion with Medium 199 alone at 37°C for an equilibration period of 2.5 h, perfusion with Medium 199 containing 10 mU/ml AVP for 30 min caused a prompt and significant (P < 0.05) decrease in the oxytocin level of up to 60% of that before AVP perfusion, whereas Medium 199 containing 0.1 mU/ml AVP had no effect on oxytocin efflux. This finding suggests that AVP may be involved in the regulation of oxytocin release from the hypothalamo-pituitary system.
The effect of propylthiouracil and methimazole on the peripheral conversion of thyroxine to 3,5,3'-triiodothyronine in athyreotic thyroxine-maintained rats
Authors: van Doom J. , Roelfsema F. , van der Heide D.
Published: December 2008

Abstract. The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions.

PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU.

In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland.

In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3.

In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important.

These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.
Effect of hypo- and hyperthyroidism on the balance between helper and suppressor T cells in rats
Authors: Pacini F. , Nakamura H. , DeGroot L. J.
Published: December 2008

Abstract. The proportion of total, helper and suppressor T lymphocytes among mononuclear cell preparations from blood and spleen of rats made hypo- and hyperthyroid was measured using three monoclonal antibodies specifically directed against total, helper and suppressor T cells.

Compared to normal rats, hypothyroid (thyroidectomized or treated with 6-propyl-2-thiouracil (PTU)) rats had a decreased proportion of suppressor T cells in the spleen, which produced an increase in the helper/suppressor T cells ratio. The opposite alterations (increased suppressor T cells and decreased ratio) was found in the blood of the same animals. Triiodothyronine (T3) added to PTU in the drinking water prevented these alterations. Animals treated with high doses of T3 for 17 days did not develop any alteration either in the proportions or in the ratio of helper/suppressor T cells. Our results suggest that hypothyroidism but not hyperthyroidism alters the normal balance between helper and suppressor T cells in rats.
Insulin release in aging: the role of glyceraldehyde
Authors: Premdas Francis H. , Molina Joseph M. , Lipson Loren G.
Published: December 2008

Abstract. Glucose-stimulated insulin release is decreased from pancreatic islets of older rats. The mechanism for this and its relationship to the hyperglycaemia of aging remain to be fully elucidated. We have recently shown that adenylate cyclase activity is reduced in islets from older rats and this might, in part, account for the decreased insulin release. It has been shown, however, that islet glucose oxidation is also reduced in aging. In an attempt to gain further insight into the biochemistry of this age-related decrease in insulin release, we investigated D-glyceraldehyde-stimulated insulin secretion.

Simultaneous experiments were performed on islets from 2 and 13 month old rats to determine insulin release in response to 2.8 mM or 16.7 mm d-glucose or 2.8 mm d-glucose + 2.5, 5.0, 7.5, 10.0 or 14.4 mm d-glyceraldehyde. Islets were incubated for 30 min at 37°C in a metabolic shaker bath and the media were then assayed for insulin by conventional radioimmunoassay.

Insulin secretion in response to 2.8 mm d-glucose was similar in the two groups of islets (9.8 ± 0.9 pg insulin islet−1min−1 from old vs 8.9 ± 1.0 from the young control rats, P < 0.2). Insulin release was diminished by 32% from islets of older rats in the presence of 16.7 mm d-glucose compared with islets from young control rats (84.0 ± 5.6 pg insulin islet−1min−1 from older animals vs 123.5 ± 10.7 from controls, P < 0.001). In the presence of 2.8 mm d-glucose + all concentrations of d-glyceraldehyde used, insulin release was similar from islets of older and young rats.

From these results, it appears that the diminished insulin release from islets of older rats involves not only changes in the adenylate cyclase system, but also may involve changes in glucose metabolism at a rate-limiting step in stimulus-secretion coupling before the metabolism of the trioses.
Ontogeny of salivary peptide P-C like immunoreactivity in human pancreatic B-cells
Authors: Ito Seiki , Isemura Satoko , Saitoh Eiichi , Sanada Kazuo , Suzuki Toshimitsu , Shibata Akira
Published: December 2008

Abstract. An immunohistochemical study using antisera against proline rich salivary peptide P-C and insulin, glucagon, somatostatin and pancreatic polypeptide antisera was carried out on the foetal pancreas at different stages and on the newborn infant's, infant's, child's and adult pancreas to examine the time at which salivary peptide P-C like immunoreactivity appeared in the human pancreas. Salivary peptide P-C like immunoreactive cells first appeared as a few scattered cells in the foetal pancreas after 16 weeks of gestation and gradually increased in numbers during gestation. The cells corresponded only to insulin immunoreactive cells in the foetal, newborn infant's, infant's, child's and adult pancreas. Only some of the insulin immunoreactive cells in the foetal pancreas contained salivary peptide P-C like immunoreactivity while the majority of those in the infant's pancreas and all those in the child's and adult pancreas did so. The findings, together with the fact that the full sequence of salivary peptide P-C is identical to the COOH-terminal 44 amino acid residues of Salivary Protein C, led to the possibility that peptide P-C like immunoreactivity in the human pancreatic B-cells was not a moiety of the precursor of insulin and pro-insulin, but a moiety of Salivary Protein C. It has been suggested that, in saliva, Salivary Protein C aids in maintenance of the calcium concentration. Based on the hypothesis that peptide P-C like immunoreactivity in the human pancreatic B-cells may play some role in insulin release through the maintenance of the calcium concentration, the present finding seems to explain the fact that the mechanism for insulin release in the foetal pancreas is immature in spite of sufficient biosynthesis of insulin.
Kinetics of hepatic thyroxine 5'-deiodinase
Authors: Kamikubo Keita , Nakamura Shigenori , Horike Seiichi , Sakata Shigeki , Yasuda Keigo
Published: December 2008

Abstract. The enzymatic kinetic constants of 5'-deiodination of thyroxine in the rat liver were determined by studying the enzymatic activity at several sets of concentrations of thyroxine and dithiothreitol. Parallel increases in apparent Vmax and Km for thyroxine were observed by increasing the concentration of dithiothreitol. Doublereciprocal replots of these apparent values vs the dithiothreitol concentration gave straight lines. These results provide further evidence for a ping-pong mechanism of the enzymatic process. The 'true' Km values for thyroxine and dithiothreitol were computed to be 16 ± 5 μm and 1.2 ± 0.4 mm, respectively. The Vmax was 126 ± 23 pmol/mg protein/min.
Thyroid autoimmunity in hyperprolactinaemic disorders
Authors: Ferrari C. , Boghen M. , Paracchi A. , Rampini P. , Raiteri F. , Benco R. , Romussi M. , Codecasa F. , Mucci M. , Bianco M.
Published: December 2008

Abstract. Circulating thyroglobulin antibodies (TgAb) and microsomal antibodies (MsAb) and thyroid function (total and free T4 and T3, TSH basal and after TRH) have been evaluated in 92 hyperprolactinaemic patients (82 females and 10 males; 9 with macroprolactinoma, 22 with microprolactinoma, 4 with acromegaly, 5 with organic lesions of the hypothalamus, 2 with empty sella, 2 with idiopathic hypopituitarism, 2 with primary hypothyroidism, and 46 with idiopathic hyperprolactinaemia). Thyroid function was normal in all cases except 3 with hypothalamic disease and central hypothyroidism, the 2 patients with primary hypothyroidism and 2 with thyrotoxicosis (one due to Graves' disease and one to autonomous thyroid adenoma). High titres of TgAb (≥1/1250) and/or MsAb (≥ 1/1600) were found in the subject with Graves' disease, in one acromegalic, in the 2 primary hypothyroids, and in 12 women with either adenomatous or idiopathic hyperprolactinaemia; low titres of one or both antibodies were found in 9 other euthyroid women and in the one with toxic adenoma. In a control population of 185 subjects studied with the same methods, the prevalence of TgAb and/or MsAb positive (low titres) was 3.3% in females and 2.5% in males. Diffuse thyroid hyperplasia was clinically detectable in 12 euthyroid women and in the one with Graves' disease; 3 others had been previously operated for nodular goitre with histological evidence of Hashimoto's thyroiditis (2 cases) or for a cold nodule; a single thyroid nodule was present in the woman with toxic adenoma and in one euthyroid woman. Most of these subjects also had circulating TgAb and/or MsAb, and a few had increased TSH secretion. No significant differences were found in mean thyroid hormone and TSH levels between euthyroid hyperprolactinaemic subjects and healthy controls, but TRH-stimulated TSH levels were significantly higher in thyroid antibodies positive than negative subjects. These data, in agreement with a few previous reports, suggest that autoimmune thyroid disorders (especially asymptomatic autoimmune thyroiditis) occur in hyperprolactinaemic women with a prevalence far exceeding that observed in many surveys in the general population.
Thyroid function and bone turnover
Authors: Bijlsma J. W.J. , Duursma S. A. , Roelofs J. M. M. , der Kinderen P.J.
Published: December 2008

Abstract. The mechanism of thyroid action on bone was studied in 15 patients with thyrotoxicosis and 14 patients with hypothyroidism. The patients were studied twice: when they were thyrotoxic or hypothyroid and when they had returned to a euthyroid state. Parameters of bone turnover showed a decrease when hyperthyroid patients became euthyroid: serum calcium (2.51 ± 0.04 vs 2.38 ± 0.03 mmol/l, P< 0.05), acid phosphatase (11.7 ± 0.7 vs 8.3 ± 0.4 U/l, P < 0.01), alkaline phosphatase (124 ± 11 vs 98 ± 8 U/l, P <0.05), the calcium/creatinine ratio (1.03 ± 0.31 vs 0.43 ± 0.07, P <0.01) and the hydroxyproline/creatinine ratio in the urine (69.9 ± 12 vs 20.7 ± 2.4, P < 0.01). These parameters showed an increase when hypothyroid patients became euthyroid: serum calcium (2.36 ± 0.03 vs 2.48 ± 0.04 mmol/l, P < 0.01), alkaline phosphatase (60 ± 4 vs 84 ± 8 U/l, P < 0.05) and the hydroxyproline/creatinine ratio in the urine (15.9 ± 4.3 vs 25.3 ± 3.2, P < 0.05). Changes in the calcium regulating hormones, parathyroid hormone, calcitonin and vitamin d metabolites, were not observed when hyperthyroid patients became euthyroid. When hypothyroid patients were treated a decrease in serum levels of 1.25-dihydroxyvitamin d (32.6 ± 4.6 vs 17.9 ± 2.5 ng/l, P <0.01) was observed. Serum growth hormone levels decreased when hypothyroid patients became euthyroid (4.3 ± 0.5 vs 2.6 ± 0.4 mU/l, P < 0.01). The possible mechanisms of thyroid action on bone are discussed. The presented findings are in accordance with a direct effect of thyroid hormones on bone in thyrotoxicosis. An additional factor could be somatomedin, that might also be involved in changes in bone turnover in hyper- and hypothyroidism.
Pathophysiologic control of nuclear triiodothyronine receptor capacity
Authors: DeGroot Leslie J. , Rue Paul A.
Published: December 2008

Abstract. Mechanisms involved in the reduced T3 receptor capacity found in a variety of pathophysiologic states were investigated by in vitro assessment of T3 receptor-nuclei interaction using tissue prepared from rats. In nuclei from immature animals, nuclear uptake of receptor was reduced, release was accelerated, and these alterations could account for the reduced nuclear receptor capacity. The functions reached the normal adult condition by 30–50 days. Nuclei from animals starved for 72 h showed no change in release of receptor, a 15% decrease in uptake, and 48% decrease in total binding capacity, indicating that the major effect is related to diminished supply of receptor, presumably due to reduced synthesis in the extranuclear compartment. Glucagon administration produced no change in receptor release, 25% decrease in receptor uptake, and nearly equivalent 33% decrease in binding capacity. Alteration in receptor uptake could account largely for changes induced by glucagon. Animals studied 24 h after hepatectomy had a 53% decrease in total binding capacity, but no change in uptake or release, indicating that reduced receptor synthesis is the primary abnormality. Administration of α-amanitin caused a 30% diminution in the binding capacity in the nuclei, without change in uptake and release, and cycloheximide caused an 87% decrease in binding capacity, with minimal change in uptake and no change in release. In both instances the alterations are interpretable as diminished synthesis and availability of receptor, rather than alterations in binding receptor to chromatin. The major cause of diminished receptor capacity appears to be reduced cytosolic synthesis of receptor, with reduction in retention by chromatin-associated factors playing a significant role in immature animals, and during glucagon treatment.
Occurrence of γ-trace in the calcitonin-producing C-cells of simian thyroid gland and human medullary thyroid carcinoma
Authors: Löfberg H. , Grubb A. , Davidsson L. , Kjellander B. , Strömblad L.-G. , Tibblin S. , Olsson S.-O
Published: December 2008

Abstract. γ-trace, a microprotein occurring in neuroendocrine cells, was demonstrated by immunohistochemical technique to be present in the calcitonin-producing C-cells of normal simian thyroid gland and of human medullary thyroid carcinoma. A comparatively high concentration of γ-trace was demonstrated in tissue extract of neoplastic C-cells. The immunoreactive protein found in the extract had a molecular weight and electrophoretic mobility characteristic for γ-trace.
Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites
Authors: Ishida Hitoshi , Seino Yutaka , Tsuda Kinsuke , Takemura Jiro , Nishi Sigeo , Ishizuka Seiichi , Imura Hiroo
Published: December 2008

Abstract. In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-hydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.
Changes in plasma kininogen levels in rats before ovulation, and after treatment with luteinizing hormone and oestradiol-17β
Authors: Smith Caroline , Perks A. M.
Published: December 2008

Abstract. The pre-ovulatory fall in plasma kininogens in rats with 4 day oestrous cycles started between 12.00 and 15.00 h pro-oestrus, reached a maximum decline of 51% by 18.00 h pro-oestrus, and started to recover before ovulation. Because these changes appeared to correspond with the LH-surge, and to follow the peak in plasma oestradiol-17β levels, both of these hormones were tested for possible effects on plasma kininogens. Intracardiac injections of 110 IU of equine LH into dioestrous rats were followed by a decline of 30.8 ± 6.7% in plasma kininogens, 6 h after injection (significant, P< 0.01). Values were still depressed, but recovering, 12 h after treatment; the reduction was 21.3 ± 5.8% (significant, P < 0.01). Controls showed no decline. Injections of oestradiol-17β (1.0 μg/100 g body weight) produced no significant effects. It is suggested that the LH surge may be responsible, at least in part, for the decline in plasma kininogens seen before ovulation.
Plasma somatostatin level during natural and interrupted nocturnal sleep in man
Authors: Saito Haruhiko , Saito Shiro , Kawano Noboru , Tomita Saku
Published: December 2008

Abstract. The plasma levels of somatostatin (SRIF), growth hormone (GH) and thyrotrophin (TSH) in 4 normal men were measured during nocturnal sleep on 6 nights. In the waking state, the fluctuation of plasma SRIF level was within ±2.1 pg/ml (sd) of the mean value for each individual (range of mean value, 10.7 pg/ml– 15.4 pg/ml). A marked episodic surge of GH release (peak value, 24.4 ± 6.3 ng/ml (mean ± sd)) was noted in the initial period of slow wave sleep (SWS) in all subjects, but no significant negative correlation was observed between SRIF and GH in the plasma during either increase or decrease in the GH surge. There was no relation between the distribution of the plasma SRIF concentration and the stage of sleep, including the period before sleep, judged by electroencephalography (EEG). A small, but significant, increase of plasma TSH (10.0 μU/ml) independent of the SWS-related GH burst was detected in 1 of 4 subjects, but in that period the plasma SRIF level did not change. Even when the GH surge was suppressed by interruption of SWS, the plasma levels of SRIF and TSH did not show any significant change. From these findings, it is concluded that SRIF in the peripheral plasma does not fluctuate during the sleeping period as in the waking state and that, whatever its source, it is not related to the plasma GH or TSH level in the systemic circulation.
Sodium valproate and cyproheptadine may independently induce a remission in the same patient with Cushing's disease
Authors: Koppeschaar H. P. F. , Croughs R.J. M. , Thijssen J. H. H. , Schwarz F.
Published: December 2008

Abstract. A patient with Cushing's disease was unsuccessfully treated by pituitary surgery and external pituitary irradiation.

One year later sodium valproate treatment induced a remission and finally hypocorticism developed. After drug withdrawal hypercoticism recurred. Treatment with cyproheptadine again induced hypocorticism necessitating corticosteroid substitution therapy. Biochemical characteristics of this patient included responsiveness to bromocriptine and cyproheptadine in acute tests. The study demonstrates that sodium valproate and cyproheptadine may both be effective independently in the treatment of the same patient with Cushing's disease. It is proposed that the disease is due to an ACTH producing tumour of pituitary intermediate lobe origin.
Prostaglandin D2 stimulates secretion of luteinizing hormone from pituitary gland in vitro
Authors: Miyake Akira , Tasaka Keiichi , Mori Shintaro , Saito Youichi , Aono Toshihiro
Published: December 2008

Abstract. The effect of prostaglandin D2 on the release of luteinizing hormone was studied in a superfusion system by superfusing human pituitary gland. Perfusion with 30 μg of prostaglandin D2 induced a significant increase of luteinizing hormone secretion. This is the first evidence of a direct effect of prostaglandin D2 on the secretion of luteinizing hormone from the human pituitary gland. This finding suggests the possible role of prostaglandin D2 in human reproductive function
Progesterone-controlled growth hormone overproduction and naturally occurring canine diabetes and acromegaly
Authors: Eigenmann J. Eugen , Eigenmann Rina Y. , Rijnberk Ad , van der Gaag Ingrid , Zapf Jürgen , Froesch E. Rudolf
Published: December 2008

Abstract. Female pet dogs exhibiting either glucose intolerance alone or glucose intolerance and acromegaly were investigated. Some dogs developed the disorder(s) during dioestrus and some animals developed the disorder(s) after they were given medroxyprogesterone acetate (MPA). Elevated fasting plasma glucose levels (12.3 ± 1.9 mm, mean ± sem) were accompanied by fasting hyperinsulinaemia (144 ± 21 μU/ml, mean ± sem) and drastic elevation of plasma growth hormone (GH) levels (112.6 ± 45 ng/ml, mean ± sem). An iv glucose tolerance test (IVGTT) performed on all dogs revealed non-suppressibility of GH levels and glucose intolerance. Plasma concentrations of glucose, insulin and GH during IVGTT in affected dogs differed significantly from the concentrations measured in normal dogs during the same test. MPA withdrawal and/or ovariohysterectomy (OVx-HYx) in affected animals was followed by reversal of GH levels to normal and improved glucose tolerance. Acromegaly associated soft tissue changes were also reversible after MPA withdrawal and/or OVx-HYx when GH levels had dropped. In 5 dogs which had developed diabetes during dioestrus and in which a spontaneous decrease in plasma progesterone occurred during the investigation a concomittant decrease in GH levels was observed. Plasma GH measured at different stages of pregnancy in 45 dogs was found to be elevated in one animal only. The results show that the development of spontaneous diabetes/acromegaly occurring in some female dogs is related to progestagen (progesterone/MPA) exposure and that reversal of the signs is achieved by progesterone/MPA withdrawal. The results suggest that diabetes/acromegaly in the dogs studied was caused by progesterone/MPA-evoked GH elevation. Finally, the findings also suggest that the GH axis normally not appreciably responsive to progestagen exposure in some dogs becomes and/or is paradoxically controlled by physiologic levels of endogenous progesterone or low doses of MPA.
Glucose, growth hormone, somatomedin, cortisol and ACTH changes in the plasma of unanaesthetised pig foetuses following intravenous insulin administration in utero
Authors: Spencer G. S. G. , Garssen G. J. , Colenbrander B. , Macdonald A. A. , Bevers M. M.
Published: December 2008

Abstract. Insulin tolerance tests were carried out in chronically catheterised foetal pigs. The experiment was carried out 7 days after catheterisation. The foetuses were, therefore, considered to be free from the effects of anaesthetics and stress. Under these conditions growth hormone levels were high compared with post-natal growth hormone levels but, under the favourable conditions in this study, both growth hormone and ACTH levels were lower than those found in anaesthetised or stressed foetuses. By contrast, cortisol levels were somewhat higher than those mentioned in previous reports. Somatomedin activity measured by post-natal cartilage bioassay was low.

Following iv insulin administration there was a marked depression in plasma glucose (P < 0.01), an elevation in growth hormone (P < 0.05) and an increase in ACTH (P < 0.01). Levels of cortisol and somatomedins did not change significantly. From these data it is concluded that insulin is an hypoglycaemic factor in the foetal pig and that, for the most part, the foetal pig pituitary responds to an insulin challenge in a similar way to the post-natal pig.
Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone binding globulin
Authors: Heller R. F. , Wheeler M. J. , Micallef J. , Miller N. E. , Lewis B.
Published: December 2008

Abstract. A cross-sectional study was performed to see if the previously described association between high density lipoprotein (HDL) cholesterol and plasma total testosterone concentration reflected a relationship with free testosterone or with sex hormone binding globulin (SHBG). In 295 employed middle-aged men, measurements were made of total testosterone and SHBG in serum and of testosterone in saliva, and also of plasma total and HDL cholesterol, plasma triglycerides and other factors which might influence HDL cholesterol levels such as body mass index, alcohol and smoking habits and thyroid hormone levels. In a multiple regression analysis using the GLIM package programme total testosterone concentrations had a persistent positive association with HDL cholesterol (t = 3.5, P < 0.001) – this association was independent of SHBG (which had a negative association with HDL: t = −1.8, P <0.07. The association of HDL cholesterol with testosterone was independent of and stronger than the association of HDL cholesterol with body mass index, alcohol intake and cigarette smoking. Salivary testosterone (a measure of the circulating free hormone) also had a positive independent association with HDL cholesterol. The relationship between HDL cholesterol and testosterone thus appears to reflect an association with circulating hormone levels rather than with the hormone binding globulin.
The effect of bromocriptine on luteinizing hormone levels in the lactating sow: evidence for a suppressive action by prolactin and the suckling stimulus
Authors: Bevers M. M. , Willemse A. H. , Kruip Th. A. M.
Published: December 2008

Abstract. Lactating sows (5 per group) were given no treatment or 10 mg bromocriptine orally twice daily from day 14 to 22 after parturition. Both groups were weaned at day 22. Frequent bleedings at 10 min intervals for 6 h were performed at 12, 16, 20 and 24 days after parturition. Prolactin and LH levels were measured in the collected blood samples by radioimmunoassays. Reduction of Prl by bromocriptine increased mean LH levels significantly and a further significant increase was observed after weaning. From the results it is concluded that in the lactating sow both Prl per se and the suckling stimulus are involved in suppression of LH levels.
Studies of the factors modulating antidiuretic hormone excretion in man in response to the osmolar stimulus: effects of oestrogen and angiotensin II
Authors: Vallotton Michel B. , Merkelbach Ulrich , Gaillard Rolf C.
Published: December 2008

Abstract. The aim of this study was to assess the influence of hormones known to regulate fluid and electrolyte balance on the release of antidiuretic hormone induced by raising serum osmolality.

The stimulus provoked by the infusion of a 2.5% NaCl solution induces an increase of urinary [arginine-8]vasopressin from 1.12 to 2.64 ng/h in men and from 1.65 to 7.27 ng/h in women as has been previously reported. These results were compared to those obtained in males infused with angiotensin II (All) before and during a hypertonic sodium load and in males infused with hypertonic saline on the fourth day of administration of ethinyl-oestradiol. During the combined infusion of All and then hypertonic saline, the mean hourly urinary excretion of AVP increased from 2.8 to 5.67 ng/h. Within each group the increase of urinary AVP was highly significant. The rise of urinary AVP during All infusion was significantly different from the rise observed both in untreated males and untreated females, lying in between. The mean hourly excretion rate of AVP increased before and after hypertonic saline loading from 2.65 to 5.3 ng/h in males pre-treated with ethinyl-oestradiol. The significant difference observed between males and females is reduced when males treated with oestrogen were compared to female subjects. In each group plasma renin activity decreased to low values during the salt-loading test. During oestrogen treatment PRA and plasma renin substrate rose, while urinary aldosterone remained almost unchanged.

We conclude that All stimulates the release of AVP in males and potentiates the response of AVP to the osmolar stimulus, and that oestrogen potentiates in man the release of AVP in response to the osmolar stimulus. This oestrogenic effect may account for the observed sex difference.
Iodine kinetics in patients with euthyroid multinodular goitre compared with normal subjects
Authors: Elte J. W. F. , Bussemaker J. K. , Termorshuizen W. , Goslings B. M. , Roelfsema F.
Published: December 2008

Abstract. In order to investigate whether patients with euthyroid multinodular goitre (EMG) lose more iodine through urinary excretion than is to be expected due to an elevated renal clearance of iodine and/or whether the iodine is handled differently in the thyroid of these patients than in that of normal subjects, the following data were obtained for 33 patients with EMG and 30 normal subjects: thyroid clearance (TC), absolute iodine uptake (AIU), renal 123I clearance (RC) and plasma inorganic iodine (PII).

A significantly lower PII and a higher TC was found in the goitre patients. In the control group PII appeared to be higher and TC and RC lower in the older age group (> 50 years). The difference in PII and TC is most easily explained by a higher iodine uptake in the subgroup of normal subjects over 50 years of age. AIU did not differ in any of the groups.

Thus, it may be concluded that an endogenous iodine deficiency due to elevated renal clearance of 123I is not a factor in sporadic goitre, at least in our patients. At the observed plasma iodine levels a significantly higher AIU was not found for goitrous patients.
A comparison of the effectiveness of 131I whole body scans and plasma Tg determinations in the diagnosis of metastatic differentiated carcinoma of the thyroid: a retrospective study
Authors: Hüfner M. , Stumpf H. P. , Grussendorf M. , Hermann H.J. , Kimmig B.
Published: December 2008

Abstract. In 68 patients with proved metastases of differentiated thyroid carcinoma the comparative value of the 131I whole body scan and plasma Tg measurements in establishing the diagnosis of metastasis or recurrence was analyzed retrospectively. At the time of primary therapy most metastases were diagnosed by the post-therapy scan (78%). Eight of 9 scintigraphic negative metastases in the post-therapy scan were indicated by elevated Tg levels (> 10 ng/ml). Twenty-four of 28 recurrences after a disease free interval were negative in the 2 mCi 131I scan, 18 of these patients were Tg positive. Of the 4 recurrences with positive 131I uptake all were Tg positive; two of them only during endogenous TSH stimulation.

It is conlcuded that the routine 2 mCi whole body scan is less efficient in follow-up than is generally assumed. The most important follow-up parameter for these patients is the plasma Tg which can be obtained under suppressive therapy if a sensitive assay is used. In patients with a negative post-therapy scan and a negative Tg (< 5 ng/ml) it seems justified to omit further 131I whole body control scans as long as Tg remains negative.
Inhibition of iodide accumulation by perchlorate and thiocyanate in a model of the thyroid iodide transport system
Authors: Saito Koshi , Yamamoto Kunihiro , Takai Takaji , Yoshida Sho
Published: December 2008

Abstract. The manner of inhibition of thyroid I− accumulation by perchlorate (ClO4−) and thiocyanate (SCN−) was studied using a newly developed biological model of the I− transport system. ClO4− inhibited I− accumulation in phospholipid vesicles made from thyroid plasma membrane and soybean phospholipids by decreasing Na+-dependent I− influx. The anion did not at all induce I− leakage from the vesicles. On the basis of Lineweaver-Burk plot analysis, it did not change Vmax for I− concentration. These results suggest that ClO4− is a competitive inhibitor of thyroid I− transport.

In contrast, SCN− did increase I− leakage from the phospholipid vesicles to diminish I− accumulation. This anion might cause only slight depression of Na+-dependent I− entry, if any. The results do not support the idea that SCN− may be a competitive inhibitor, in spite of the fact that the anion did not change Vmax for I− transport on the basis of Lineweaver-Burk plot analysis.
Metabolism of thyroid hormones in isolated rat hepatocytes: studies on the influences of carbamazepine and phenytoin
Authors: Aanderud Sylvi , Aarbakke Jarle , Sundsfjord Johan
Published: December 2008

Abstract. The in vitro handling of thyroid hormones was studied in isolated rat hepatocytes by measuring 1) the cellular uptake of T4, 2) the conversion of T4 to T3 and 3) the degradation of T4 and T3. The in vitro conversion of T4 to T3 increased significantly by adding ethanol 2% or carbamazepine (CBZ) 400 μm in ethanol 2% to the incubation medium. As there was no difference between ethanol and CBZ/ethanol on the T3 formation, this effect was probably caused by ethanol. The T3 formation was unaffected by phenytoin (PHT) in conc. up to 400 μm, while propylthiouracil (PTU) 100 and 400 μm inhibited the conversion completely. The T4 to T3 conversion in hepatocytes from rats pretreated with CBZ or PHT for 2 weeks was not significantly different from untreated controls. The cellular uptake of T4 was reduced by about 30% in the presence of PHT and unaltered by CBZ and ethanol. The degradation of T4 and T3 was not influenced by the in vitro addition of CBZ or PHT, nor was the degradation of T4 and T3 significantly different from untreated controls in hepatocyte suspensions from CBZ or PHT pretreated rats. Our findings suggest that the handling of thyroid hormones in isolated rat hepatocytes is not influenced by the in vitro or in vivo exposure to CBZ or PHT.