bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of truncated glucagon-like peptide-1 on pancreatic hormone release in normal conscious dogs
Authors: Kawai Koichi , Suzuki Seiji , Ohashi Shinichi , Mukai Hidehito , Murayma Yasuko , Yamashita Kamejiro
Published: June 2009

The effects of truncated glucagon-like peptide-1 (GLP-1) on insulin and glucagon release were examined in unanesthetized normal dogs. A bolus injection of GLP-1 (7-36)amide elicited a transient increase in the plasma insulin level, which brought about a decrease in the plasma glucose level. The degree of increase in plasma insulin levels with GLP-1 (7-35)OH or GLP-1 (7-37)OH was less than that induced by GLP-1 (7-36)amide. The plasma glucagon level did not increase in spite of mild hypoglycemia. The infusion of graded doses of GLP-1 (7-36)amide (6, 36, 120 ng · kg−1 · min−1 every 30 min) did not change the plasma glucose, insulin or glucagon levels significantly. The degree of increase in the plasma glucose level induced by iv glucose infusion (12 mg · kg−1 · min−1) was reduced by coinfusion of GLP-1(7-36)amide (6 ng · kg−1 · min−1), although the degree of increase in the plasma insulin level was the same as that in a control experiment (coinfusion of the vehicle). Coinfusion of GLP-1 (7-36)amide (60 ng · kg−1 · min−1) caused an augmented increase in the plasma insulin level and a reduced increase in the plasma glucose level during iv glucose infusion (17 mg · kg−1 · min−1) compared with the control experiment. The degree of decrease in the plasma glucagon level during iv glucose infusion was not affected by the coinfusion. The degree of increase in the plasma glucagon level induced by insulin hypoglycemia and the profile of the plasma glucose level at that time were not affected by the infusion of GLP-1 (7-36)amide. These results demonstrate that 1. the insulinotropic activity of GLP-1 (7-36)amide is higher than that of GLP-1(7-37)OH or GLP-1(7-35)OH; 2. GLP-1 (7-36)amide suppresses the degree of increase in plasma glucose level during iv glucose infusion by augmented insulin release, and 3. the glucagonostatic activity of truncated GLP-1 is negligible under physiological conditions.
The thyroid hormone analogue SKF-94901 and iodothyronine binding sites in mammalian tissues: Differences in cytoplasmic binding between liver and heart
Authors: Barlow John W. , Raggatt Lorna E. , Lim Chen-Fee , Kolliniatis Emily , Topliss Duncan J. , Stockigt Jan R.
Published: June 2009

The thyroid hormone analogue, SKF-94901 exhibits greater thyromimetic activity in the liver than in the heart. This difference in activity may reflect heterogeneity in the affinity of SKF-94901 for different forms of the T3 receptor. A difference in extranuclear transport of the analogue could also account for the different response of these two tissues. To distinguish between these possibilities we have examined the binding of SKF-94901 to membrane, cytosolic and nuclear preparations from liver and heart of the primate, Macaca fascicularis. Uptake of SKF-94901 into H4 liver cells was low. Binding of [125I]T3 to cell membrane preparations (Kd ≈3 μmol/l), and to nuclear extracts (Kd ≈0.2 nmol/l was displaceable by SKF-94901 with a potency 2-5% that of T3 in each case. No significant difference was observed between liver and heart for SKF-94901 binding to membranes or nuclear extract. With cytosol, [125I]T3 binding was identical in heart (Kd, 22.7±10.4 nmol/l) and liver tissue (Kd, 30.3±11.1 nmol/l). In liver, and in cardiac cytosol after preliminary washing to remove serum, iodothyronine potency was in the order T3 > T4 > rT3. The ratio of SKF-94901 to T3 concentrations which gave 50% displacement was 15.9±6.8 in the liver; and 152.3±89.1 in the heart (p<0.05). The selective tissue activity of SKF-94901 may be related to a reduced affinity of the analogue for the cytosolic binding proteins in the heart, rather than a difference in affinity for various forms of the T3 receptor.
The effect of sex hormones on bone resorption by rat osteoclasts
Authors: Tobias J. H. , Chambers T. J.
Published: June 2009

Although sex hormones are important in the attainment and maintenance of bone mass, the mechanism by which they exert their effect is unknown. We therefore tested the effects of estradiol-17β, dihydrotestosterone, and progesterone on osteoclasts, the cells that resorb bone. Osteoclasts were disaggregated from neonatal rat long bones, and incubated with or without the addition of osteoblastic cells or osteoblast-like cell lines. Bone resorption was assessed by scanning electron microscopy as the extent of excavation of the bone surface after incubation. We found dihydrotestosterone (1-100 nmol/l) and progesterone (10-1000 nmol/l) to have no significant effect on bone resorption. By contrast, E2 (1 nmol/l) reduced bone resorption in osteoclast cultures to which osteoblasts had been added, by approximately 25%, although consistent inhibition with other concentrations (0.01, 0.1, 10 nmol/l) was not observed. To our surprise, E2 was also associated with a delayed, dose-responsive, stimulation of bone resorption, in the range 0.1-10 nmol/l, in osteoclast cultures free from added osteoblastic cells. Tamoxifen, which itself had no effect on bone resorption, appeared to antagonise these E2 effects. Although the physiological significance of the stimulatory effect is unclear, we hypothesize that its presence prevented us, and previous workers, from observing doseresponsive inhibition of bone resorption by E2 in vitro.
Acupuncture in the treatment of Graves' ophthalmopathy. A blinded randomized study
Authors: á Rogvi-Hansen B. , Perrild H. , Christensen T. , Detmar S. E. , Siersbæk-Nielsen K. , Hansen J. E. M.
Published: June 2009

Seventeen patients with Graves' ophthalmopathy, all euthyroid for at least one year, were included in a blinded trial to test the effect of acupuncture twice a week during two months on the eye disease, assessed by an ophthalmologist and computed tomography of the eye muscle volume. No significant change was found in eye muscle volume, Hertel measure, palpebral aperture, intraocular pressure, Hess chart, nor was there any statistically significant improvement of the irritative conjunctival symptoms.
Sensitivity of thyrotropin secretion to TSH-releasing hormone in food-restricted rats
Authors: Rodriguez Felipe , Mellado Mario , Montoya Eladio , Jolin Trinidad
Published: June 2009

The aim of the present study was to identify the mechanisms involved in the reduction of TSH secretion during prolonged food restriction. The basal TSH secretion rate, the TSH secreted in response to TRH, both in vivo and in vitro, and the TSH, nuclear T3, and plasma membrane TRH binding sites in the pituitary were determined in rats receiving 75% (FR75), 50% (FR50) and 25% (FR25) of the food consumed by the ad libitum fed rats (controls). The basal TSH secretion rate (μg·h−1g·(100 g)−1) in FR75, FR50 and FR25 groups were decreased by 19, 42 and 74% of control values, respectively, whereas the TSH secreted in response to TRH in vivo and in vitro was reduced by 21 and 13% in FR50, and 55 and 44% in FR25, respectively, of the corresponding control values. Food restriction increased the TRH binding sites from 229 in controls to 322, 479 and 521 (fmol/mg protein), in FR75, FR50 and FR25 groups, respectively, whereas the opposite was seen in nuclear T3(controls 862, FR75 841, FR50 342 FR25 233 fmol/mg DNA). Moreover, a decrease in the pituitary TSH concentration was observed in FR50 and FR25 rats. The data suggest that an alteration in the amount of TRH reaching the pituitary gland is probably the main responsible for the low plasma TSH values during food restriction. However, an inhibitory effect at the pituitary level cannot be ruled out.
Evidence that neuronally released vasoactive intestinal polypeptide inhibits the release of serotonin from enterochromaffin cells of the guinea pig small intestine
Authors: Racké Kurt , Schwörer Harald , Agoston Denis V. , Kilbinger Heinz
Published: June 2009

Isolated small intestinal segments of the guinea pig were arterially perfused and the release of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were intra-arterially applied. The muscarine receptor agonist oxotremorine (1 μmol/l inhibited the release of 5-hydroxytryptamine by about 50%. In the presence of the neurotoxin tetrodotoxin, oxotremorine enhanced the release of 5-hydroxytryptamine by 145%, indicating that the inhibitory effect of oxotremorine was mediated by the release of a neurotransmitter. Exogenous vasoactive intestinal polypeptide ( 1-100 pmol/l inhibited the release of 5-hydroxytryptamine by about 50%, an effect antagonized by a specific antibody to vasoactive intestinal polypeptide. This antibody to vasoactive intestinal polypeptide, on its own, had no effect on the release of 5-hydroxytryptamine. However, it prevented the inhibitory effect of oxotremorine. In the presence of the antibody to vasoactive intestinal polypeptide, unlike in the presence of tetrodotoxin, oxotremorine did not stimulate the release of 5-hydroxytryptamine. In conclusion, activation of neuronal muscarine receptors in the guinea pig small intestine enhances the release of several neurotransmitters which can inhibit the release of 5-hydroxytryptamine. The present experiments provide good evidence that vasoactive intestinal polypeptide is one of them.
Effects of exogenous monoiodotyrosine on the serum levels of anterior pituitary hormones
Authors: Tan Stanley A. , Lewis John E. , Berk Lee S. , Wilcox R. Bruce
Published: June 2009

Monoiodotyrosine is a tyrosine hydroxylase inhibitor. Ingestion of one gram monoiodotyrosine caused a 10000-fold increase of serum monoiodotyrosine from basal levels of 0.69±0.20 nmol/l to a peak of 10.6±1.7 μmol/l in women and 7.1±2.3 μmol/l in men 30 min later, and the t½ was 45 min. Monoiodotyrosine stimulated PRL to a peak of 170±51 μg/l in women and 90±6 μg/l in men 30 min after the monoiodotyrosine peak, or 60 min after the ingestion. Other anterior pituitary hormones were unchanged. Dopamine infusion or L-dopa pretreatment attenuated the monoiodotyrosine effect. TRH exaggerated the PRL peak, and chlorpromazine did not increase but prolonged the hyperprolactinemia. These results suggest that dopamine synthesis inhibition may be the mechanism of PRL stimulation.
Steroid profile in serum: increased levels of sulphated pregnenolone and pregn-5-ene-3β,20α-diol in patients with adrenocortical carcinoma
Authors: Gröndal Staffan , Curstedt Tore
Published: June 2009

A serum steroid profile was determined in 11 patients with adrenocortical carcinoma, 5 with adrenocortical adenoma and 10 healthy controls. Seven of the patients with carcinoma had different forms of endocrine symptoms, and of those with adenoma 3 had Cushing's syndrome and 2 primary hyperaldosteronism. Sulphated steroids dominated in serum from both patients and controls, whereas the levels of free and glucuronated steroids were low. All patients with adrenocortical carcinoma had increased levels of sulphated pregn-5-ene-3β-ol-20-one (pregnenolone) and pregn-5-ene-3β,20α-diol compared with healthy controls and patients with adrenocortical adenoma. Serum levels of 11-deoxycortisol and/or its glucuronated metabolite tetrahydro-11-deoxycortisol were clearly elevated in 8 of the patients with carcinoma. The results are in agreement with those previously found for conjugated urinary steroids in patients with adrenocortical carcinoma. Thus, an impaired function or deficiency of 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase and in some cases also of 11β-hydroxylase could explain the findings. The sulphated pregnenolone and/or pregn-5-ene-3β,20α-diol, possibly together with free11-deoxycortisol seem to be useful for preoperative discrimination between malignant and benign adrenocortical tumours.
Unaltered pulsatile and circadian TSH release in euthyroid patients with endemic goitre
Authors: Weber Peter , Krause Ulrich , Gaffga Gabi , Brabant Georg , Manz Friedrich , Lehnert Hendrik , Schrezenmeir Jürgen , Beyer Jürgen
Published: June 2009

To evaluate the pathophysiological role of TSH in goitrogenesis we investigated pulsatile TSH secretion in 11 patients with a non-toxic goitre and in 11 healthy controls. Thyroid volume was 40 ± 10 ml in the goitre group and 15 ± 4 ml in the controls as measured by ultrasound. Blood was sampled continously via an indwelling venous catheter at 10-min intervals over 24 h. Neither the mean 24-h serum TSH levels (goitre 1.1 ± 0.5 vs controls 0.9 ± 0.4 mU/l) nor the nocturnal surge of TSH were significantly different between the two groups. The average of the TSH pulse frequency (goitre 10.8 ± 3.7 vs controls 9.6 ± 3.5 pulses/24-h) and of the TSH pulse amplitude (goitre 0.4 ± 0.2 vs controls 0.3 ± 0.1 mU TSH/l as analysed by DESADE programme (detection of secretory activity by discrete deconvolution) did not differ in the two groups. Furthermore, there was no correlation between the volume of the thyroid gland and the dynamics of the TSH secretion. We conclude that our data do not suggest a relevant pathophysiological role of TSH secretion in the development of non-toxic goitre in man.
Heat stress and hydrocortisone are independent stimulators of triiodothyronine-induced growth hormone production in cultured rat somatotrophic tumour cells
Authors: Shapiro Lawrence E. , Katz Claire P. , Wasserman Susan H. S. , DeFesi Charles R. , Surks Martin I.
Published: June 2009

We have reported that, in cultured GC cells, the stress of incubation at 41°C enhances thyroid hormone stimulation of growth hormone (GH) in a manner similar to the effects observed in a model of nonthyroidal disease in rats. Since glucocorticoids are potentially involved in stress responses both in vivo and in cell culture, we studied the role of glucocorticoid in the enhancement of (which are rat somatotrophic tumor cells) triiodothyronine (T3)-induced GH synthesis due to heat stress. Hydrocortisone addition increased T3-induced GH synthesis and GH mRNA content in cultured GC cells at both 37°C and 41°C. Depletion of glucocorticoid endogenous to serum supplement of the tissue culture medium did not prevent the enhancement of T3-induced GH synthesis that occurred during incubation at 41°C. The levels and affinity of glucocorticoid cytosolic receptors were not enhanced during incubation at 41°C. Lastly, no change in the sedimentation coefficient of the cytosolic glucocorticoid receptor or in its translocation into the nucleus occurred during incubation at 41°C. Thus, the enhancement of T3-induced GH production in GC cells by heat stress appeared independent of the effect of glucocorticoids and not mediated through glucocorticoid receptors.
Regulation of testicular P-450 cholesterol side-chain cleavage and P-450 C17-20 lyase/C17 hydroxylase enzymes in the neonatal and adult rat
Authors: Lu Yin , McDonough Alicia A. , Farley Robert A. , Warren Dwight W.
Published: June 2009

Adult Leydig cells respond to LH or hCG with an initial stimulation of testosterone secretion followed by LH receptor down-regulation and blockade of androgen biosynthesis. In contrast, fetal Leydig cells respond with increased LH receptor number and enhanced steroidogenesis. In this study, the molecular mechanisms of high-dose hCG treatment on steroidogenesis in adult and neonatal testes (containing predominantly the fetal generation of Leydig cells) were examined using two recombinant DNA clones specific for enzymes of the rat steroidogenic pathway (P-450 cholesterol side-chain cleavage enzyme, P-450scc and P-450 17α-hydroxylase/C17-20 lyase, P-450c17). We treated adult (60 days of age) and neonatal (2 days of age) rats with a single high dose of hCG (600 IU/kg), sc. The high dose of hCG caused neonatal testicular P450scc and P450c17 mRNA levels to increase, and stimulated adult testicular P450scc mRNA levels, but caused a decrease in adult P450c17 mRNA levels. These studies suggest that high doses of hCG regulate testosterone production differently in adult and fetal Leydig cells at a pretranslational level of the P450c17 enzyme, while mRNA for P450scc is stimulated in both the adult and fetal Leydig cell.
A human TSH-secreting adenoma: Endocrine, biochemical and morphological studies. Evidence of somatostatin receptors by using quantitative autoradiography. Clinical and biological improvement by SMS 201-995 treatment
Authors: Polak Michel , Bertherat Jerome , Li Jacques Y. , Kujas Michelle , Le Dafniet Michelle , Weizani Hussein , Van Effenterre Remy , Epelbaum Jacques , Turpin Gerard
Published: June 2009

An invasive TSH-secreting adenoma inducing mild hyperthyroidism was diagnosed in a 16-year-old male. Initial surgical treatment led to a temporary clinical and biological improvement. Recurrence of the thyrotoxicosis was treated with the somatostatin analogue, SMS 201-995 (octreotide) with normalization of the serum thyroid hormone levels with a dose of 200 μg per day. With immunoelectron microscopy, the tumour cells appeared poorly granulated with small secretory granules located at the periphery of the cells; only part of those were immunoreactive with an anti-TSHβ monoclonal antibody. No specific TRH binding site was found in a tumour membrane preparation. By quantitative autoradiography, somatostatin specific binding sites were as numerous in the TSH-secreting tumour as in control GH-secreting tumours. Binding kinetics and guanosine triphosphate dependency of the binding were equivalent in the TSH and GH tumours tested. Although all of the tumour cells displayed the same ultrastructural features, some were non-immunoreactive, suggesting that they could secrete an altered form of TSH. The absence of TRH receptors in the tumour cells is in accordance with previous reports on this type of tumour. We confirm the efficiency of octreotide treatment in this case of neoplastic TSH inappropriate secretion. The therapeutic effect of octreotide goes along with the presence of a high density of guanine nucleotide-dependent somatostatin binding sites in the tumour cells.
Effects of cytidine 5'-diphosphocholine administration on basal and growth hormone-releasing hormone-induced growth hormone secretion in elderly subjects
Authors: Ceda Gian Paolo , Ceresini Graziano , Denti Licia , Magnani Dario , Marchini Lorenzo , Valenti Giorgio , Hoffman Andrew R.
Published: June 2009

The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p<0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85± 185.1 vs 248.9±61.4 μg · l−1 · (120 min)−1; p=0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.
Bone mass in totally thyroidectomized patients. Role of calcitonin deficiency and exogenous thyroid treatment
Authors: Gonzalez Diana C. , Mautalen Carlos A. , Correa Pedro H. , El Tamer Elias , El Tamer Sara
Published: June 2009

Calcitonin has an uncertain role in the preservation of bone mass. Since surgical thyroidectomy abolishes the calcitonin secretion in response to calcium, the bone mineral density at the radius shaft and lumbar spine was measured in 60 patients (5 men, 16 premenopausal, 34 postmenopausal euparathyroid and 5 postmenopausal hypoparathyroid women) who had undergone near total thyroidectomy for thyroid cancer 8.4±0.7 years before the study. All patients were maintained on suppressive doses of thyroid hormones. Bone mineral density values of the radius shaft (expressed as Z-score) of 34 postmenopausal euparathyroid women was significantly below the normal average (mean ± sem = −0.59 ±0.2; p=0.01). Bone mineral density of the lumbar spine was also below the normal average although the difference only approached statistical significance (−0.36±0.2; 0.05 <p<0.1). The bone mineral density of neither the radius nor the spine differed from normal levels in the premenopausal women and the postmenopausal hypoparathyroid women. Unexpectedly, the bone mineral density of the spine was significantly increased in the 5 thyroidectomized men. The results indicate that thyroidectomized women have a diminished bone mass after the menopause only if parathyroid function is normal. Since the patients were receiving thyroid hormone at suppressive doses, the present study is not able to separate the relative contributions of calcitonin deficit and exogenous thyroid on bone mass loss.
Calf and forearm blood flow in patients with primary hyperparathyroidism and in control subjects
Authors: Broulik P. D. , Spáĉil J.
Published: June 2009

Using a venous occlusion air-filled plethysmograph we measured the blood flow in the limbs in 10 patients with established primary hyperparathyroidism and control subjects. The patients had highly raised ionized calcium and immunoreactive parathormone levels, and the diagnosis was verified at operation. In all patients resting blood flow values in the limbs were increased compared with control subjects. Peak blood flow after 5 min of ischemia was also increased, however, not significantly. This clinical study supports previous studies on a vasoactive effect of parathormone.
Intact parathyroid hormone concentration and cyclic AMP metabolism in thyroid disease
Authors: Fraser W. D. , Logue F. C. , MacRitchie K. , Wilson R. M. , Gray H. W. , Beastall G. H. , O'Reilly D. StJ.
Published: June 2009

In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (>2.60 mmol/l) intact PTH was below the assay detection limit (<0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84).
HLA-DR3 and variations of the T cell receptor β gene in Graves' disease
Authors: Schifferdecker Ekkehard , Manfras Burkhard , Kühnl Peter , Holzberger Gerhard , Boehm Bernhard O.
Published: June 2009

The association of Graves' disease with two allelic forms of the T cell receptor β-chain gene (Bgl II restriction fragments 9.2/10.0 kb) was analysed in Caucasians suffering from Graves' disease (N=54), randomly selected controls (N=68), and HLA-DR3 homozygous typing control subjects (N=12). While gene frequencies did not vary in the latter two groups, a significant reduction of 9.2 kb homozygosity was observed in patients with Graves' disease (11 vs 32%, x2=7.68, p<0.01, RR=0.26). The excess of the 9.2/10.0 kb heterozygosity in patients, which is restricted to the DR3-positive individuals, did not reach significance. The increase in heterozygosity of genomic T cell receptor β-chain polymorphisms may be attributed to the role the β-chain plays in autoantigen recognition in Graves' disease.
Immunoreactive insulin-like growth factor binding protein-3 in the culture of human luteinized granulosa cells
Authors: Hamori Miklos , Blum Werner F. , Török Attila , Stehle Ralph , Waibel Eberhard , Cledon Philippe , Ranke Michael B.
Published: June 2009

Granulosa cells from human preovulatory follicles were cultured under serum-free conditions to investigate the presence of immunoreactive insulin-like growth factor binding protein-3 (IGFBP-3). IGFBP-3 levels were measured by a radioimmunoassay developed against the acid-stable subunit of the protein. The antiserum had no cross-reactivity to the low molecular weight GH-independent IGFBP-1. Granulosa luteal cells exhibited a continuous release of IGFBP-3 into the culture medium during the whole time (6 days) of the incubation. A dose-dependent increase in IGFBP-3 was observed when the cells were treated by dibutyryl cAMP. Cycloheximide suppressed almost completely both the basal and the stimulated production of IGFBP-3. The smallest effective dose of dibutyryl cAMP enhancing the progesterone release was lower than that for IGFBP-3. The different time course of IGFBP-3 and progesterone secretion to dibutyryl cAMP treatment, as well as the failure of progesterone to elicit IGFBP-3 increase alone, do not support the participation of progesterone in the IGFBP-3 production of granulosa cells. It is concluded that 1. immunoreactive IGFGBP-3 is produced by cultured granulosa luteal cells; 2. its synthesis is regulated by physiological intracellular mechanisms.
Beneficial effects of GH replacement therapy in adults
Authors: Christiansen Jens Sandahl , Jørgensen Jens Otto Lunde
Published: June 2009

Growth hormone deficiency in adults is associated with psychosocial maladjustment, reduced muscle strength, and reduced exercise capacity. Body composition is significantly altered, with increased fat and decreased muscle volume as compared with healthy subjects. Kidney function is subnormal. Epidemiological data suggest premature mortality owing to cardiovascular disease in hypopituitary patients. Short-term GH treatment trials have shown improved psychosocial performance, normalization of body composition, increased muscle strength, improved exercise capacity, increased cardiac performance, and normalization of kidney function. Thus GH replacement therapy in GH-deficient adults exhibits potential long-term beneficial effects. A number of important questions have to be addressed before long-term GH replacement therapy in GH-deficient adults can be considered on a routine basis.
Heterogeneity of human luteinizing hormone. Hydrophobic interaction chromatographic fractionation of some preparations
Authors: van Ginkel Leendert A. , Somers Harry H. J. , Loeber J. Gerard
Published: June 2009

The heterogeneity of human luteinizing hormone was investigated with high performance hydrophobic interaction chromatography on a TSK phenyl-5PW column using an ammonium sulphate gradient. Recovery of individual subunits, expressed as immunochemical activity, was in the order of 90%. Recovery of the intact hormone was less, approximately 25%. The technique appeared to be independent of the charge heterogeneity of the individual subunits. Each component as obtained by hydrophobic interaction chromatography showed considerable charge heterogeneity when studied by subsequent isoelectric focusing. Nontheless, all chromatography fractions derived from either subunit showed the same collection of isoelectric values, quantitatively only differences for the β-subunits could be detected. Heterogeneity of the individual subunits was clearly demonstrated after incubation of the preparations at 37 or 56°C. The heterogeneity of the β-subunit observed after incubation at 56°C was different to the heterogeneity after incubation at 37°C. After incubation at 56°C, an additional component, with a longer retention time, developed directly from the intact molecule. The component is unstable and is transformed to one of the components detected also after incubation at 37°C. Based on these results the existence of two populations of intact LH molecules with respect to their thermal stability is hypothesized.
Endocrine and metabolic effects of life-long food restriction in rats
Authors: Stokkan Karl-Arne , Reiter Russel J. , Vaughan Mary K. , Nonaka Keico O. , Lerchl Alexander
Published: June 2009

The effects of chronic (40%) food restriction from 6 weeks of age were studied in 28-month-old male Fischer-344 rats; the results were compared with ad libitum-fed, old and young male rats at 28 and 3 months of age, respectively. Pituitary luteinizing hormone was similar in all old rats and was significantly lower than in young rats. In old ad libitum-fed, but not in food-restricted rats, serum levels of LH, testosterone and T4 were significantly lower than in young rats. Serum levels of T3 did not differ between young and old rats. Type-II 5'-deiodinase activity in brown adipose tissue was similar in both groups of old animals and was significantly depressed as compared with that in young rats. Serum levels of triglycerides were significantly depressed in food-restricted rats, but were significantly increased in ad libitum-fed rats as compared with young rats. Both groups of old rats had significantly elevated serum levels of cholesterol over that in young rats, but the level was significantly lower in food-restricted as compared to ad libitum-fed animals. The results are consistent with the notion that life-long food restriction tends to preserve the activity of many metabolic functions.
Oxytocin influences preovulatory follicular development and advances ovulation in rats
Authors: Robinson Gillian , Evans John J.
Published: June 2009

Oxytocin has been shown to advance gonadotropin secretion in pro-estrus rats. The effects that oxytocin-induced changes have on the ovary were investigated in this study. Oxytocin administered to rats at proestrus 09.00 h, 10.00 h and 11.00 h advanced follicular growth, progesterone secretion, and the time of ovulation. However, both treated and control groups of rats ovulated similar numbers of oocytes and the oocytes released were of similar fertility. Because oxytocin has been shown to induce early LH and FSH release the effects of oxytocin administration on the ovary were possibly an indirect action involving the pituitary. The results of this investigation indicate that exogenous oxytocin alters, the timing but not the fertility of periovulatory events.
Growth hormone specific stimulation of mitosis by size-fractionated serum from patients with growth hormone insufficiency: A study on the rat lymphoma cell line, Nb2
Authors: Luthman Marguerite , Wallerman Ella , Roos Paul , Werner Sigbritt
Published: June 2009

The aim was to investigate the bioactivity of a high-molecular weight human growth hormone, identified following molecular sieve chromatography of serum. Nine patients with pituitary disease and GH insufficiency were studied. All patients had non-detectable levels of immunoreactive GH, <0.2 μg/l, in diurnal serum profiles. GH bioactivity was determined before and after size-fractionation of serum. The bioassay is based on the finding that a rat lymphoma cell line, Nb2, proliferates in the presence of lactogens. GH and PRL immunoreactivities were measured by radioimmunoassays. Pronounced GH immunoreactivity was found in fractions of sera from 7 out of the 9 patients and of 2 of 4 control sera, particularly in fractions corresponding to the elution volume of high-molecular weight proteins (>160 kD). PRL immunoreactivity was only detected in fractions corresponding to the elution volume of monomeric PRL. Unfractionated serum had a dose-dependent mitogenic effect on the Nb2 cells. GH-antibodies could not inhibit this effect. Fractions of serum obtained from the patients stimulated Nb2 cell division as well. The mitogenic effect of serum fractions could be inhibited by GH-antibodies. Thus, high-molecular weight GH circulating in patients with GH insufficiency were shown to exert a GH-specific bioactivity in vitro after size-fractionation.
Adenosine 3',5'-monophosphate in relation to inhibition of cervical smooth muscle activity in early pregnant women
Authors: Norström A. , Bryman I.
Published: June 2009

Contractile activity was registered in strips of cervical tissue obtained by needle biopsy from women in the first trimester of pregnancy. Dibutyryl cyclic adenosine-3',5'-monophosphate (5 × 10−6mol/l), isobutyryl methylxanthine (10−4mol/l), and forskolin (10−510−4mol/l), the latter two drugs known to increase the levels of endogenous cAMP, inhibited spontaneous muscle activity. The levels of tissue cAMP were determined in strips during relaxation induced by prostaglandin E2 or purified porcine relaxin and compared with cAMP levels in strips from the same women during contractile activity. Exposure to prostaglandin E2 but not to relaxin was followed by increased levels of cAMP. It is suggested that cAMP has a role as a second messenger in the prostaglandin E2-mediated relaxation of cervical smooth muscle.
Presence of CRH-binding protein in amniotic fluid and in umbilical cord plasma
Authors: Suda Toshihiro , Iwashita Mitsutoshi , Sumitomo Takashi , Nakano Yoriko , Tozawa Fumiko , Demura Hiroshi
Published: June 2009

CRH-binding protein was present in the amniotic fluid and in the umbilical cord plasma after 15 weeks and 24 weeks of pregnancy, respectively. The size of the CRH-binding protein was similar to that in the peripheral blood from normal subjects. The level of the binding of CRH-binding protein in the umbilical cord plasma during the third trimester of pregnancy was also similar to that in the peripheral blood of neonates and normal adult subjects. The binding of CRH-binding protein was temporarily decreased at 40 weeks of pregnancy. These results indicate that fetal CRH-binding protein seems to be produced at least in the second trimester of pregnancy.
Effect of insulin-like growth factor 1 on steroidogenesis in cultured human granulosa cells
Authors: Bergh Christina , Olsson Jan-Henrik , Hillensjö Torbjörn
Published: June 2009

The effect of IGF-I on steroidogenesis in human granulosa cells was studied. Granulosa cells were obtained from follicles of both natural and stimulated cycles. The cells were cultured 4 to 6 days and the effect of IGF-I (1 to 100 μg/l) on basal, LH- and FSH-stimulated steroidogenesis was studied. It was found that in granulosa cells from follicles of natural cycles, FSH as well as IGF-I significantly stimulated progesterone and estradiol production in a majority of the experiments. A synergistic effect of FSH and IGF-I could be seen when low (1 and 10 μg/l) concentrations of the two hormones were used. Also in granulosa luteal cells from stimulated cycles a stimulatory effect of IGF-I on estradiol as well as progesterone production was observed. The present results suggest that IGF-I in combination with gonadotropins has a physiological role in the human follicle in controlling differentiation of the granulosa cells.
Muscarinic regulation of phospholipase A2 and iodide fluxes in FRTL-5 thyroid cells
Authors: Di Girolamo Maria , D'Arcangelo Daniela , Bizzarri Cinzia , Corda Daniela
Published: June 2009

FRTL-5 thyroid cells express a muscarinic receptor which inhibits the phospholipase C activity in a pirenzepine-insensitive manner. We here report that the cholinergic agonist carbachol decreases in these cells the steady-state iodide content, an effect correlated with the iodination of thyroglobulin and with thyroid hormone formation. Several signal pathways may be involved in this phenomenon since carbachol in addition to inhibiting phospholipase C, increased the arachidonic acid release and modified the adenylyl cyclase activity. In FRTL-5 cells, arachidonic acid is released via the direct stimulation of phospholipase A2 by a pirenzepine-sensitive muscarinic receptor coupled to a GTP binding protein sensitive to pertussis toxin. Regarding adenylyl cyclase, carbachol potentiated the thyrotropin-induced stimulation of the enzyme, whereas it did not affect the basal levels of cAMP. In vitro binding studies revealed the presence of two muscarinic binding sites. To summarize, the analysis of signal pathways and of in vitro binding sites indicates a complex muscarinic regulation of thyroid function, which includes the modulation of iodide fluxes.
The influence of growth hormone and thyroxine on iodothyronine deiodinase activity in the liver, kidney and brown adipose tissue in hypophysectomized rats
Authors: Gøtzsche Liv S. Bjørn-Hansen , Flyvbjerg Allan , Marshall Sally , Jørgensen Karin D. , Weeke Jørgen
Published: June 2009

The effects of GH and T4 substitution on peripheral iodothyronine deiodinase activity in the liver, kidney and brown adipose tissue of hypophysectomized rats were investigated. Animals were treated with GH (140 μg hGH/day), T4 (3 μg/day), GH plus T4 (same doses), or saline. Rats were killed 0, 4, 7 or 11 days after treatment was started. Non-hypophysectomized, age matched rats were killed after 0 and 11 days and served as controls. GH plus T4 restored body weight gain to normal, whereas GH alone and T4 alone did not. Tissue deiodinase activity and T3 concentrations were severely depressed in the hypophysectomized rats compared with non-hypophysectomized controls (to less than 10%). GH substitution in hypophysectomized rats led to a slight but significant elevation in tissue iodothyronine deiodinase activity in the liver and kidney, without concomitant increases in T3. Deiodinase activity in brown adipose tissue did not differ from that in saline-treated controls. T4 administration normalized deiodinase activity and tissue T3 content in all the evaluated tissues. GH plus T4 resulted in a lesser increase in deiodinase activity than T4 alone in the liver and kidney (p<0.01 at day 11), whereas no significant difference was observed in brown adipose tissue. In conclusion, GH stimulates iodothyronine deiodinase activity of the liver and kidney in hypophysectomized rats. Moreover, when GH is administered together with T4, the T4-stimulated enzyme activity in the liver and kidney is downregulated, suggesting that GH attenuates (or modulates) the T4 effect on this specific enzyme activity.
Evidence for a pathological reduction in brain dopamine metabolism in idiopathic hyperprolactinemia
Authors: Paradisi Roberto , Grossi Gabriele , Pintore Angela , Venturoli Stefano , Porcu Eleonora , Capelli Maurizio , Flamigni Carlo
Published: June 2009

The role of brain catecholamine activity in the neuroendocrine regulation of the dopamine-PRL system in idiopathic hyperprolactinemia was investigated by high-performance liquid chromatography with electro-chemical detector. We measured urinary dopamine, norepinephrine, epinephrine, vanillylmandelic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid and total 3-methoxy-4-hydroxyphenylglycol levels in 12 women with idiopathic hyperprolactinemia before and during either peripheral dopa-decarboxylase blockade, by carbidopa, or dopamine β-hydroxylase blockade, by disulfiram. Homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations were significantly lower (p<0.001 and p<0.005, respectively) in patients with idiopathic hyperprolactinemia compared with those in 12 control subjects in the early follicular phase, whereas they were similar to those in the control subjects in the pre-ovulatory phase. Dopamine, norepinephrine, epinephrine, vanillylmandelic acid and 3-methoxy-4-hydroxyphenylglycol concentrations were similar to those of the control subjects in both phases of the cycle. During carbidopa administration the levels of all urinary catecholamines and metabolites were unchanged, except that of dopamine which dropped remarkably (p<0.001). During disulfiram administration dopamine, homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations increased (p<0.05, p<0.001 and p<0.005, respectively) and those of norepinephrine, vanillylmandelic acid and 3-methoxy-4-hydroxyphenylglycol decreased (p<0.05, p<0.001 and p<0.005, respectively), whereas epinephrine levels remained unaltered. These data support the existence of a quantitatively reduced brain dopamine activity in idiopathic hyperprolactinemia.
The interaction of GHRH with TRH in acromegaly: a controlled study
Authors: Looij Bert-Jan , Roelfsema Ferdinand , Frölich Marijke , Kruseman Arie C. Nieuwenhuijzen
Published: June 2009

In a single-blind placebo-controlled study, the effect of an iv bolus injection of 100 μg GHRH(1–29)NH2 on the response to 200 μg TRH was assessed in 10 untreated patients with acromegaly to determine whether GHRH interacts with TRH in acromegaly, as previously described in healthy subjects. The combination of GHRH(1–29)NH2 with TRH resulted in a larger increment of peak and of integrated plasma TSH and PRL levels than after TRH alone. GHRH alone had no effect on TSH secretion and only a modest effect on PRL secretion. These findings suggest that in acromegaly, like in healthy individuals, GHRH potentiates the TSH response to TRH and that the effects of GHRH and TRH on PRL secretion are additive.
Stimulation of steroid secretion by adrenocorticotropin injections and by arginine vasopressin infusions: no evidence for a direct stimulation of the human adrenal by arginine vasopressin
Authors: Bähr V. , Hensen J. , Hader O. , Bölke T. , Oelkers W.
Published: June 2009

Arginine vasopressin stimulates the secretion of adrenocorticotropin. A direct stimulatory effect of AVP on cortisol as well as aldosteron secretion has been postulated by several investigators. To study the possible role of a direct stimulatory action of AVP on the adrenal cortex, normal volunteers were treated with incremental injections of ACTH or with incremental infusions of AVP which raised plasma AVP levels to a maximum of 256±16 pmol/l. In both situations, a significant (p<0.001) linear correlation between plasma ACTH and plasma cortisol was observed. The regression coefficients were not different (p>0.5). Plasma aldosterone was stimulated by both treatments, but the weakly positive correlation between plasma ACTH and plasma aldosterone was not significant for either stimulus. Thus, in man, a direct stimulatory effect of AVP on cortisol secretion cannot be demonstrated. A direct effect of AVP on aldosterone cannot be definitely excluded, but is certainly of minor importance.
Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: A double-blind study
Authors: Verhelst J. A. , Froud A. L. , Touzel R. , Wass J. A. H. , Besser G. M. , Grossman A. B.
Published: June 2009

Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.
Thyroid epithelial cell proliferation in xenotransplanted human toxic nodular goitre is increased by Graves' IgG
Authors: Smeds Staffan , Jörtsö Erik , Tegler Lennart
Published: June 2009

Human toxic nodular goitre tissue was xenotransplanted to athymic mice. Transplant function was analysed as 18-h thyroid transplant uptake of iodide-125 at day 21 and again at 10 weeks after transplantation. Graves' IgG or IgG from healthy donors was given intraperitoneally daily day 22-35. Epithelial cell proliferation in thyroid tissue transplants from human toxic nodular goitre and from normal thyroid glands was analysed by continuous [3H]thymidine administration for 4 days between day 21 and 24 and for 12 days between day 21 and 33 in separate series given daily injections of Graves' IgG or normal IgG during the same period. After administration of Graves' IgG, the 18-h iodide-125 uptake by the toxic nodular tissue transplants was 7 times higher at 10 weeks than at 3 weeks. Control IgG gave a corresponding 1.6-fold increase. The fraction of labelled cells after [3H]thymidine incorporation was 18 and 56% in toxic nodular goitre transplants and 4 and 48% in normal thyroid tissue transplants after daily Graves' IgG administration for 4 and 12 days, respectively, but only 1.3% in both types of tissue transplants after administration of normal IgG. Graves' IgG therefore seems to be able to stimulate cell proliferation in toxic nodular goitre tissue.
Congenital hypothyroidism in two cats due to defective organification: data suggesting loosely anchored thyroperoxidase
Authors: Sjollema B. E. , den Hartog M. T. , de Vijlder J. J. M. , van Dijk J. E. , Rijnberk A.
Published: June 2009

Two cats with congenital hypothyroidism are described. In vivo discharge of accumulated labelled iodide by perchlorate administration revealed defective organification of iodide, which was complete in one cat and partial in the other. In the cat with the partial organification defect, thyroid tissue was obtained for biochemical studies. No membrane-bound peroxidase activity could be demonstrated. The activity was found in the 100000 × g supernatant. It is suggested that the loose enzyme anchoring caused decreased availability of peroxidase and as a consequence reduced capacity for organic binding of trapped iodide.