bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum profiles and short-term metabolic effect of pituitary and authentic biosynthetic human growth hormone in man
Authors: Jørgensen J. O. L. , Flyvbjerg A. , Dinesen J. , Lund H. , Alberti K. G. M. M. , Ørskov H. , Christiansen J. S.
Published: December 2008

Abstract. In a double-blind cross-over study we compared pituitary and methionine-free biosynthetic human growth hormone (P-hGH and B-hGH) with respect to pharmacokinetics and short-term metabolic effects in 9 hypopituitary children. They treated themselves for 4 weeks with 2 IU sc daily at 20.00 h. After admittance to hospital 2 IU was given: im the first day, and sc the second. They then switched over to the alternative preparation. The serum profiles of B- and P-hGH were identical. Comparing im and sc adsorption, the latter was slower and resulted in smaller areas under the curves, indicating greater local degradation.

Both preparations caused identical increases in somatomedin-C, but slightly more sustained after sc injection. Plasma glucose, plasma glucagon, and serum insulin fluctuated within normal ranges. The glucose profile pointed at a modest anti-insulin effect of hGH when given in the morning. The concentration in the blood of lactate, alanine, glycerol and B-OH-butyrate, and in serum of triglyceride, cholesterol and carbamide revealed no abnormalities with either hGH preparation. Finally, no development of anti-GH or E. coli polypeptide antibodies was seen. In conclusion, the pharmacokinetics and short-term metabolic effects of B-hGH and P-hGH were identical.
HLA associations in insulin-dependent diabetes mellitus diagnosed during pregnancy
Authors: Møller-Jensen B. , Buschard K. , Buch I. , Mølsted-Pedersen L. , Kühl C. , Jakobsen B. K. , Svejgaard A.
Published: December 2008

Abstract. Sixty out of 63 patients with insulin-dependent diabetes mellitus (IDDM) diagnosed during pregnancy in the Diabetes Centre at the Department of Obstetrics and Gynaecology, Rigshospitalet, Copenhagen, were re-examined 2–16 years after diagnosis. Fourty-six patients were currently insulin-treated and the remaining 14 patients were all severely glucose intolerant. HLA-typing was carried out in 41 of these patients. The HLA phenotype distribution showed a highly significant difference from that of non-diabetics but was similar to that seen in IDDM not related to pregnancy. Thus, pregnancy may constitute a special trigger mechanism for IDDM, but the subsequent pathogenic mechanisms are probably the same as those involved in other cases of IDDM.
Effects of multiple injections of luteinizing hormone on secretion of pregnane compounds from polycystic ovaries of rats exposed to constant light
Authors: Sawada Tsutomu , Kosaka Tadashi , Ichikawa Shigetaka
Published: December 2008

Abstract. Differences in the secretion of pregnane compounds by ovaries with cystic follicles of rats exposed to constant light (light-induced oestrous rats) and by ovaries with normal follicles of early pro-oestrous rats were studied. Some rats were injected iv with 2 μg of LH to stimulate the secretion of steroids 30 min before their blood was sampled. The injection greatly increased the secretion of progesterone by both kinds of ovaries. The secretion of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one also increased in normal rats, but not in the polycystic ovaries of light-induced oestrous rats, which suggested that the 5α-reductase activity was low. The pre-ovulatory LH surge is absent in light-induced oestrous rats, so a classic approach was taken to circumvent the probable deficit in the cyclic release of LH; we gave multiple injections of 10 μg of LH. Five such injections were given at intervals of 4 days, and ovarian venous blood was collected 4 days after the last injection. Cystic follicles in the ovaries of rats disappeared when the injections of LH were given every 4 days. The production of 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one from the ovaries of such rats was significantly higher (P < 0.01) than in controls given multiple injections of saline. These results suggest that the low 5α-reductase activity in polycystic ovaries of light-induced oestrous rats may be due to the absence of an LH surge from the pituitary gland.
Minor interference of low-dose pulses of GnRH with the positive effect of oestradiol on the pituitary gland
Authors: Koiter T. R. , van der Schaaf-Verdonk G. C. J. , Pols-Valkhof N. , Schuiling G. A.
Published: December 2008

Abstract. In the ovariectomized rat we investigated the effects of prolonged treatment with oestradiol and 'physiological' pulses of exogenous GnRH on the GnRH-responsiveness of the pituitary gland. Rats were for 20 h pre-treated with either GnRH (3-ng pulses of 3 min duration every 20 min) or saline and for 19 h with either oestradiolbenzoate (OB; 3 μg/sc injection) or oil. Then LH and FSH responses were evoked by continuous test infusions of GnRH at the rates of either 60, 100, 150 or 1000 ng/h, lasting 10 h. It appeared that, irrespective of pre-treatment with either GnRH or saline, OB caused an increase of the maximal LH and FSH responses (that is the responses to the maximal stimulus of 1000 ng GnRH/h), and an increase of the GnRH-sensitivity of the pituitary gland, as far as the FSH secretion is concerned. GnRH pulses caused, irrespective of pre-treatment with OB or oil, a decrease of the GnRH-sensitivity of the pituitary gland, as well as a decrease of the maximal FSH response and of the pituitary FSH content. It was concluded that low-dose pulses of exogenous GnRH desensitize the pituitary gland and deplete the pituitary FSH stores, but do not change the positive effect of oestradiol on the maximal gonadotropin response.
Influence of luteinizing hormone and prostaglandin F2α on progesterone secretion in superfused bovine luteal tissue slices
Authors: Hoedemaker Martina , Grunert Kirsten , Maas D. H. A. , Grunert E.
Published: December 2008

Abstract. Tissue slices from bovine corpus luteum from Days 12 or 13 of the oestrous cycle were super-fused for 8 h, and the progesterone secretion under the influence of prostaglandin F2α (PGF2α) and/or LH was measured. PGF2α at concentrations of 0.28 to 2800 nmol/l medium did not affect the basal progesterone secretion, whereas higher doses (7000 to 28 000 nmol/l) induced a slight increase in hormone secretion. LH, 3.4 nmol/l, caused an increase in the progesterone concentration in superfusates which exceeded the control levels (P < 0.01). This luteotropic effect of LH was not influenced by simultaneous addition of 28 to 2800 nmol/l PGF2α. PGF2α, 2800 nmol/l, did not inhibit progesterone secretion, when administered together with 0.034 to 34 nmol LH/l. Pre-superfusion with 2800 nmol/l PGF2α had no effect on the LH-stimulated increase in progesterone secretion. It is concluded that in cattle, a direct cellular effect of PGF2α, antagonizing the luteotropic function of LH, may be of less importance than other possible direct and indirect PGF2α actions.
Thyrotropic activity of crude hCG in FRTL-5 rat thyroid cells
Authors: Ballabio M. , Sinha A. K. , Ekins R. P.
Published: December 2008

Abstract. The presence of thyroid stimulating activity in partially purified hCG was investigated using, as bioassay system, iodide uptake in rat thyroid FRTL-5 cells. The biological responses evoked by hCG were tested after neutralisation with monoclonal and polyclonal antisera to hTSH and hCG, and after fractionation on Sephadex G-100. The molar amounts of TSH and hCG in respective preparations were calculated assuming an activity of 30 IU/mg and 19 IU/mg, respectively, for bTSH and hTSH, and of 14 000 IU/mg for hCG. A dose-dependent response, paralleling that evoked by hTSH, was observed in a concentration range of 0.1–4 μmol/l hCG; 1 μmol of hCG was equivalent to 50 pmol of bTSH and 132 pmol of hTSH. The thyrotropic activity coeluted with hCG immunoactivity on Sephadex G-100. Incubation with monoclonal anti-hTSH antibodies did not affect the stimulatory ability of hCG preparation, indicating that it was not due to hTSH contamination. Similarly, a pretreatment with monoclonal and polyclonal anti-hCG antibodies did not significantly alter the iodide uptake response induced by hCG. These results indicate that the thyrotropic activity in partially purified hCG is not due to the presence of aspecific contaminants, but to a substance structurally related to hCG in terms of molecular weight. However, it appeared to differ from hCG immunologically, suggesting the hypothesis that minor modifications in the molecular structure may confer thyrotropic activity on hCG, altering its immunoreactive potency.
Light microscopical morphometry, immunocytochemistry, and clinical correlations of pituitary adenomas at various stages of oncocytic transformation
Authors: Weber Tina , Saeger Wolfgang , Lüdecke Dieter K.
Published: December 2008

Abstract. In a series of 124 pituitary adenomas displaying oncocytic alterations, we studied the degree of oncocytic transformation by light microcopical and morphometrical means for semiquantitative analysis. We established three groups with different percentages of oncocytically transformed cells for comparison of clinical and immunocytochemical data. Of the patients, 32.3% exposed adenomas with less than 50% oncocytic alterations (group I), whereas 22.6% showed tumours with oncocytic transformations between 51% and 75% (group II). Oncocytic parts consisting of more than 75% of the tumour cells were found in 41.1% of the patients (group III). All three groups differed in the rate of immunocytochemically positive cases, but not in sex distribution, tumour size, and rate of recurrency. Immunocytochemical analyses for PRL and GH (81 vs 78 adenomas) showed a decline of immunohistochemically positive adenomas with increasing proportions of oncocytic transformation for both hormones. Whereas in group I 38% of the adenomas were PRL-positive and 15% GH-positive, group III displayed only 9% PRL-positive and 3% GH-positive adenomas. The results display the correlation between the increasing volume of oncocytic transformation and its effect on decreasing hormone content in pituitary adenomas.
Plasma levels of growth hormone-releasing hormone and somatostatin in response to a mixed meal and during sleep in children
Authors: Rosskamp R. , Becker M. , Haverkamp F. , Thomas B. , Brühl S. , Klumpp J. , Liappis N.
Published: December 2008

Abstract. Following a mixed meal, plasma levels of GHRH, GH, SRIH and insulin were measured in 7 prepubertal children with constitutional delay of growth and adolescence (CDGA) and in 3 children with proven GH-deficiency which responded to GHRH-injection. In children with CDGA, plasma levels of GHRH increased between 60 and 120 min (10.1 ± 1.2 ng/l vs 25.5 ± 4.4 ng/l; P < 0.01). Although no GH increase occurred in patients with GH-deficiency, their plasma GHRH increases were comparable to those in CDGA children. No time relationship was present between circulating GHRH and GH, SRIH, or insulin, nor was there any correlation between their integrated hormone response areas. Sleep-induced plasma GHRH, GH and SRIH values were determined in 10 prepubertal children with CDGA. Spontaneous variations of plasma GHRH and GH values occurred with no temporal or quantitative relationship. SRIH values did not change during nocturnal sleep. In one child with GH-deficiency, comparable GHRH plasma fluctuations occurred, although GH values were all below 1 μg/l. Our results support the concept that circulating GHRH does not only represent hypothalamic GHRH, but derives mainly from extrahypothalamic sources, possibly from the gastrointestinal tract.
Reduction of urinary albumin excretion after 4 years of continuous subcutaneous insulin infusion in insulin-dependent diabetes mellitus
Authors: Dahl-Jørgensen Knut , Hanssen Kristian F. , Kierulf Peter , Bjøro Trine , Sandvik Leiv , Aagenæs Øystein
Published: December 2008

Abstract. Urinary albumin was studied in 45 patients with insulin-dependent diabetes in a 4-year prospective randomized trial, comparing continuous sc insulin infusion (CSII), multiple insulin injections, and conventional treatment with twice daily injections. Strict blood glucose control was obtained with CSII and multiple injections, better than with conventional treatment (2P < 0.01): mean glycosylated haemoglobin (% HbA1±sem) after 4 years: CSII 9.0 ± 0.4%; multiple injections 9.4 ± 0.4%; conventional treatment 10.5 ± 0.5. A total of 696 24-h urine specimens were collected. After 4 years of CSII from the time of randomization, urinary albumin excretion was reduced (26 ± 5 to 16 ± 4 mg/24 h, mean ± sem, 2P < 0.01), when compared with conventional treatment (2P=0.01) where no change was observed (21 ± 4 to 22 ± 6 mg/24 h, n.s.). The reduction observed during multiple injection treatment was not significant (17 ± 3 to 14 ± 3 mg/24 h). Long-term nearnormoglycaemia may influence the mechanisms leading to albuminuria in diabetes, if introduced at an early stage of the disease.
Receptors for epidermal growth factor and thyrotropin in thyroid carcinoma
Authors: Mäkinen Tuulikki , Pekonen Fredrika , Franssila Kaarle , Lamberg Bror-Axel
Published: December 2008

Abstract. The EGF and TSH receptor properties in malignant thyroid tumours and adjacent normal thyroid tissues were characterized using radioreceptor assays. Ten patients with papillary, 4 with medullary, 1 with Hürthle cell type follicular carcinoma, and 2 with anaplastic thyroid carcinoma were studied. In 10 out of 12 patients with papillary and anaplastic thyroid carcinomas, more EGF receptors were found in the neoplastic tissue than in the adjacent normal tissue (P < 0.01). The affinity of the EGF receptors varied between patients (from 0.5 × 109 1/mol to 1.9 × 109 1/mol), but was in each patient the same in the neoplastic and in the normal tissue. In medullary carcinomas and a follicular Hiirthle thyroid carcinoma, the EGF receptor content was very low. The receptor number was unaltered or decreased in papillary carcinomas when compared with adjacent normal tissue. In anaplastic medullary and follicular (Hürthle cell) carcinomas, the neoplastic tissue had very few high affinity TSH receptor sites. The alterations in TSH receptor characteristics when thyroid neoplastic tissue was compared with adjacent normal tissue did not correlate to changes in EGF receptor characteristics. Our results demonstrate that the amount of EGF receptors in papillary and anaplastic thyroid carcinomas differ significantly from that in follicular and medullary carcinomas and that alterations in EGF receptor content in malignant thyroid tissues are independent of TSH receptor content.
Day/night serotonin levels in the pineal gland of male BALB/c mice with melatonin deficiency
Authors: Vollrath L. , Huesgen A. , Manz B. , Pollow K.
Published: December 2008

Abstract. Studies from another laboratory have shown that several strains of laboratory mice have a genetic defect for melatonin synthesis. In non-deficient species, melatonin synthesis undergoes a typical, β-adrenergically regulated day/night rhythm with low melatonin levels during daytime and high levels at night, the precursor serotonin showing an inverse behaviour. This study examines whether a day/night rhythm of pineal serotonin levels exists in melatonin-deficient male BALB/c mice. Mice kept under a lighting schedule of 12 h light (lights on at 07.00 h) and 12 h dark were killed at 13.00 and 01.00 h, respectively. Serotonin amounted to 12-15 ng/pineal and did not show regular day/night differences. Administration of the β-adrenergic agonist, isoproterenol, which is known to affect melatonin synthesis in a number of species, was without effect on pineal serotonin levels. Melatonin and two of the melatonin-forming enzymes, serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were below the detection limit in the pineal. It is concluded that in melatonin-deficient BALB/c mice, pineal serotonin synthesis is apparently intact. In BALB/c mice, serotonin synthesis and release do not appear to be directly or indirectly regulated by β-adrenergic mechanisms.
In vitro studies in primary aldosteronism:
Authors: Pham-Huu-Trung Marie T. , Duclos J. M. , Pagny J. Y. , Bogyo A. , Leneuve P. , Girard F.
Published: December 2008

Abstract. The spontaneous glucocorticoid production in control adrenal cells (N = 10) and in the adenoma cells (N = 15) exhibited comparable geometric mean values: 1.896 nmol/ml/4–5 × 105 cells per 2 h (confidence limits: 0.428–8.391) and 1.852 nmol/ml (0.326–12.241), respectively. The same results were obtained for the three samples of nodular hyperplasia cells. When cortisol and corticosterone were measured separately, there was no significant difference between the outputs for control cells and those for pathological cells. Baseline aldosterone production in control cells showed a geometric mean of 2.525 pmol/ml (0.236–27.192). In the 15 adenomas, spontaneous production was extremely important: 57.297 pmol/ml (3.357–976.692). The difference was highly significant (P < 0.0005). Aldosterone levels in the 3 samples of nodular hyperplasia cells were not different from the control values. In 9 out of the 15 adenomas, aldosterone responses to 10−10 mol/l ACTH, expressed as stimulated/basal production, were above normal: 3.58 ± 0.86 (sem) against 1.48 ± 0.08 (P < 0.025). In the remaining 6 and in the 3 samples of nodular hyperplasia cells, there was a slight or no response. Angiotensin II (AII) stimulated both adenoma and nodular hyperplasia cells to varying degrees, without any obvious difference between these two categories. A combination of ACTH (10−12 mol/l) and All (10−12 mol/l) had a synergistic action on aldosterone production in cells classed in the adenoma group. These findings demonstrate that despite the abnormal rate of aldosterone formation in adenoma cells, the production rate of corticosterone and cortisol remains normal. They unmask two functional categories with regard to ACTH in the adenoma group. Finally, they underline the relative insensitivity of nodular hyperplasia cells to ACTH.
Study of the role of histidyl, tyrosyl, α- or ε-amino residues in the specific binding of 3,5,3'-triiodothyronine to rat liver nuclear receptors
Authors: Brtko Julius , Knopp Ján
Published: December 2008

Abstract. The role of histidyl, tyrosyl, α-or ε-amino residues of rat liver nuclear receptors for the specific binding of T3 was studied by chemically modifying the receptor molecule. The kinetics of the formation of N-carbethoxyhistidyl derivative from histidyl groups of nuclear receptors by diethylpyrocarbonate was examined. The modified nuclear receptor fraction was separated from diethylpyrocarbonate by gel filtration and the T3 binding parameters (Ka and MBC) at pH 8.0 were tested by Scatchard plot analysis. At 0.1 mmol/l diethylpyrocarbonate, the value of Ka was significantly (P < 0.01) decreased without any change in maximal binding capacity (MBC). The modification of α- or ε-amino groups of nuclear receptors by excess of trinitrobenzenesulfonic acid, 6.3 mmol/l at pH 8.5, resulted in a 4-fold increase in MBC of T3 specific binding without any change in Ka. In addition, acetylation of tyrosyl residues of nuclear receptors at pH 7.5 with an excess of 24 mmol/l N-acetylimidazole was performed. No changes in nuclear receptor Ka or MBC were observed after N-acetylimidazole treatment. Histidine and/or amino groups of the receptor molecule seem to hold a key position in the generation of the biologically active T3-nuclear receptor complex in the rat liver.
Lacking evidence for release of thyroid hormones from circulating thyroglobulin during subtotal thyroidectomy
Authors: Date J. , Blichert-Toft M. , Feldt-Rasmussen U. , Haas V.
Published: December 2008

Abstract. The effect of subtotal thyroid resection for thyrotoxicosis on concentrations of serum thyroid hormones and thyroglobulin (Tg), was determined in 10 patients during operation and the subsequent 18 days. Mean serum Tg responded drastically, increasing from a pre-operative value of 0.30 nmol/l to a peak value of approximately 26 nmol/l during operation followed by a gradual decline to levels lower than before surgery on day 18. Mean serum total thyroxine was 114 nmol/l pre-operatively and free thyroxine index (FT4I) 105 units. Both fluctuated only slightly during operation. Postsurgically, the mean values decreased to below 50% of the pre-operative level. Mean serum total triiodothyronine (TT3) was 1.46 nmol/l pre-operatively. It decreased during operation, reaching a nadir of 0.55 nmol/l on day 2, whereafter the concentration increased slightly. Mean serum reverse T3 (rT3) was 0.45 nmol/l pre-operatively, increased 62% during surgery, and decreased postsurgically. The mean value of serum thyroid stimulating hormone (TSH) was 0.61 mU/l pre-operatively and remained below 1 mU/l during and after operation, but from day 10 concentration began to rise steadily. It is concluded that the vast release of Tg during thyroid resection did not contribute to the concentration of serum T4 to an extent of clinical relevance.
Comparison of the facilitative roles of insulin and insulin-like growth factor I in the functional differentiation of granulosa cells: in vitro studies with the porcine model
Authors: Maruo Takeshi , Hayashi Masato , Matsuo Hiroya , Ueda Yasuo , Morikawa Hajime , Mochizuki Matsuto
Published: December 2008

Abstract. The facilitative effects of insulin and IGF-I were compared in vitro with regard to induction of differentiated functions of porcine granulosa cells. The monolayers were maintained under serum-free conditions in the absence or presence of porcine FSH (20 μg/l), with or without graded doses of insulin or IGF-I. Concurrent treatment with IGF-I and FSH produced morphological differentiation and augmented LH/hCG receptor binding together with an enhancement in progesterone and estradiol secretion relative to treatment with FSH alone. IGF-I alone was incapable of exhibiting these effects. Insulin synergized with FSH to facilitate the granulosa cell functions except estradiol secretion. Maximal effective dose of IGF-I was 100 μg/l which is within the physiological concentration in vivo, whereas that of insulin was 1.0 mg/l, which is 1000-fold higher than the physiological level. Although the maximal effective doses of IGF-I and insulin produced a comparable increment in progesterone secretion and LH/hCG receptor induction, combined treatment with IGF-I and insulin did not prove additive. [125I]IGF-I binding revealed that specific IGF-I receptors with two classes of binding sites are present on porcine granulosa cells. No distinct differences were detected between IGF-I receptors of granulosa cells from small, medium and large follicles. Insulin was approximately 100-fold less active than IGF-I in competing for [125I]IGF-I binding. These findings suggest that porcine granulosa cells possess specific IGF-I binding sites which may mediate the cytodifferentiative actions of insulin-like peptides. Since IGF-I is more potent than insulin in amplifying the actions of FSH and maximally exerts the cytodifferentiative effects at the physiological concentration, it is likely that IGF-I plays the more important role in granulosa cell differentiation in synergy with FSH.
Plasma vasopressin and oxytocin levels in intact goats and in castrated goats given testosterone
Authors: Thornton S. N. , Delaney C. E. , Chapman C.
Published: December 2008

Abstract. Oxytocin, vasopressin, cortisol and testosterone levels in the plasma were measured by radioimmunoassay in intact male goats as well as in prepubertally castrated goats injected daily, for 2 weeks, with oil vehicle and then, for 4 weeks, with testosterone propionate in oil to study the influence of gonadal steroids on posterior pituitary hormones. Packed cell volume, plasma osmolality and sodium concentration were also measured in all blood samples. Plasma levels of oxytocin, vasopressin and cortisol were similar in the intact and oil-injected castrated goats. Testosterone treatment significantly increased plasma levels of oxytocin (P < 0.01) in castrated goats but the increased levels were similar to those seen in the intact goats at the same time of year. Plasma levels of cortisol and vasopressin were unaffected by testosterone propionate treatment, whereas packed cell volume was significantly decreased (P < 0.01). Testosterone treatment of castrated male goats appears not to have any action on pituitary hormones and oxytocin increases in the spring in both intact and castrated male goats.
GHRH-induced GH response in patients with senile dementia of the Alzheimer type
Authors: Cacabelos Ramón , Niigawa Hisayoshi , Ikemura Yoshiaki , Yanagi Yuji , Tanaka Shigemi , Rodríguez-Arnao María D. , Gómez-Pan Antonio , Nishimura Tsuyoshi
Published: December 2008

Abstract. To clarify the functional state of the somatotropinergic system at the hypothalamo-hypophyseal level in senile dementia of the Alzheimer type, the GHRH test was performed in three groups of subjects: a) healthy elderly subjects; b) early onset senile dementia patients; and c) late onset senile dementia patients. Intravenous administration of GHRH(1–44)NH2 (100 μg) elicited a marked plasma GH response with a maximum peak (709.54 ± 259.0 pmol/l; P < 0.005) 60 min after injection in patients with early onset senile dementia, but no significant response was detected in the other two groups. Electroencephalographic recording showed that GHRH modifies brain bioelectrical activity, decreasing frequency (0.52 ± 0.15 Hz) and increasing amplitude (8.25 ± 4.5 μV) of the electroencephalogram basic rhythm. The evaluation of mental performance and behaviour with a battery of different tests for mental assessment revealed that GHRH induces transient clinical changes in psychomotor behaviour. According to these results, it seems likely that the somatostatin deficiency reported in senile dementia of the Alzheimer type may account for the enhanced GHRH-induced GH response observed in patients with early onset senile dementia. In consequence, the GHRH test might constitute a useful antemortem marker for senile dementia of the Alzheimer type if the present results can be replicated in early stages of the disease.
Interleukin-1 potentiates glucose stimulated insulin release in the isolated perfused pancreas
Authors: Wogensen Lise D. , Mandrup-Poulsen Thomas , Markholst Helle , Mølvig Jens , Lernmark Åke , Holst Jens J. , Dinarello Charles A. , Nerup Jørn
Published: December 2008

Abstract. The acute effects of recombinant human interleukin-1 beta (rIL-1) on basal and glucose-stimulated insulin release were investigated in the isolated perfused pancreas. At a concentration of 20 μg/l rIL-1 had no effect on basal insulin release, but increased the total amount of insulin released during first and second phase insulin release in response to 20 mmol/l D-glucose in the rat pancreas (P < 0.05). In addition, 26 μg/l of rIL-1 potentiated insulin release in response to square wave infusions of stimulatory concentrations of glucose (11 mmol/l) in the porcine pancreas. We hypothesize that IL-1 in the systemic circulation may affect B cell function in vivo.
Ultrastructural evidence for oxytocin in the rat anterior pituitary gland
Authors: Morel G. , Chabot J.-G. , Dubois P. M.
Published: December 2008

Abstract. OT is synthetized in the hypothalamus. These neurons project to the posterior lobe of the pituitary and the external zone of the median eminence. In order to localize OT in the male rat anterior pituitary we have used immunocytochemistry on ultrathin sections in target cell(s) obtained by cryoultramicrotomy. OT-like immunoreactivity was observed in lactotropes only. No immunoreactivity was observed in gonadotropes, somatotropes, corticotropes or thyrotropes. In lactotropes, immunoreactivity was localized at the plasma membrane level, in the cytoplasmic matrix and around the secretory granules, but not in the other organelles, and in the nucleus. No reaction was observed by using either non-immune serum or anti-OT serum incubated with OT. No modification of OT-like immunoreactivity was observed by using antiOT serum incubated with heterologous peptides. These results 1) provide immunocytological evidence for the presence of OT in the anterior pituitary gland; 2) indicate the presence of this peptide in one particular cell type, and 3) support the hypothesis that OT could have a direct participation in the regulation of the PRL release.
Insulin-like growth factors in the Göttinger miniature-pig
Authors: Zenobi Peter D. , Guler Hans-Peter , Zapf Jürgen , Froesch E. Rudolf
Published: December 2008

Abstract. IGF I was determined by a radioimmunoassay and IGF II by a radioreceptorassay in 20 Göttinger miniature (mini)-pigs and 13 domestic pigs of different weight and age. Immunoreactive IGF I serum levels of mini-pigs were similar to those of domestic pigs in corresponding age-classes (150–250 and 100–270 μg/l, respectively). No differences were detectable between receptor-reactive IGF II serum levels in mini-pigs (150–200 μg/l) and domestic pigs (110–270 μg/l) nor did the biological insulin-like activites (measured in the rat fat cell assay) differ in mini- and domestic pigs (81–100 and 71–98 mU insulin/l, respectively). IGF I and IGF II decreased drastically after hypophysectomy in one of the mini-pigs. Intravenous bolus injections of 30 μg/kg of recombinant human IGF I in 4 mini-pigs caused a similar degree of hypoglycemia (nadir of blood glucose 1.33 ± 0.61 mmol/l) as 0.15 IU insulin/kg, followed by a sharp growth hormone peak. We conclude that the marked difference between mini- and domestic pigs regarding body size is unrelated to serum levels of IGF I and II, a lack of response of tissues to IGF I or a reduced growth hormone secretory capacity in the mini-pig.
Comparison of thyroid stimulating activities measured by cyclic AMP production, those by radioiodine uptake in FRTL-5 cells and TSH-binding inhibitory activities in patients with hyperthyroid and euthyroid Graves' diseases
Authors: Kasagi Kanji , Hatabu Hiroto , Tokuda Yasutaka , Arai Keisuke , Iida Yasuhiro , Konishi Junji
Published: December 2008

Abstract. By using an assay measuring cAMP production in FRTL-5 thyroid cells, thyroid stimulating antibodies (TSab) were detected in all of 15 patients with euthyroid Graves' disease (EG) and of 26 patients with hyperthyroid Graves' disease (HG). There was no significant difference between TSab activities in EG and in HG. In an effort to elucidate why EG patients remain euthyroid in spite of having TSab, we investigated the effect of the patient's crude immunoglobulin fractions on 125I uptake in FRTL-5 thyroid cells, one of the indices of stimulation subsequent to cAMP production. The 125I uptake stimulating (IUS) activity was positive in 46.7% (7/15) of EG patients and 88.5% (23/26) of HG patients, being significantly lower in the former than in the latter (P < 0.02). Although the IUS activities significantly correlated with TSab activities in 41 patients with EG and HG (r = 0.784, P < 0.001), the ratio of IUS to TSab in EG tended to be lower than that in HG. TSH-binding inhibitor immunoglobulins (TBII) activities in EG patients were negative or weakly positive, being significantly lower than those in HG patients (P < 0.001). Thus, the ratios of TBII to both TSab and IUS activities were significantly higher in HG than in EG (P < 0.01, P < 0.001, respectively). The in vitro IUS activities also correlated with TBII activities (r = 0.441, P < 0.001) and in vivo 99mTc thyroid uptake (r = 0.401, P < 0.001) in both EG and HG patients. The EG patients with positive IUS activities displayed smaller goitre size and lower 99m thyroid uptake in comparison to 19 HG patients with a similar range of IUS activities. There was a good correlation between thyroid weight and 99mTc thyroid uptake (r = 0.827, P < 0.001). In conclusion, lower IUS activity and/or smaller goitre size in EG than in HG, which may lead to lower thyroidal uptake of 99mTc and presumably radioiodine in vivo, might be a factor responsible for keeping EG patients euthyroid despite the presence of TSab.
The influence of pulsatile GnRH administration to the ovariectomized rat on the pituitary response to GnRH and the occurrence of spontaneous LH pulses
Authors: Lambalk C. B. , van Rees G. P. , Schoemaker J. , de Koning J. , van Dieten J. A. M. J.
Published: December 2008

Abstract. Otherwise untreated adult ovariectomized rats were given pulses of GnRH (5 ng/100 g body weight iv) once every 60 or 120 min for 24 or 96 h. On the first and last day of the experiment plasma LH was estimated during the administration of GnRH pulses. Endogenous LH pulses between exogenously generated LH pulses were observed in nearly all animals on both the first and the last day, without any change in nadir and amplitude values. Shortly after an injection of GnRH, the spontaneous LH pulses were fewer than expected. The number of these pulses, however, increased again with time after the injections. The response to exogenous GnRH was reduced on the last day of the experiment. However, not all GnRH injections led to LH pulses. Most injections which did not result in an LH pulse appeared to be given within 15 min after a preceding endogenous LH pulse. The results obtained are in agreement with the hypothesis of an acute short-lasting desensitization of the pituitary gland caused by exogenous as well as endogenous pulses of GnRH.
Formation of leukotriene B4 and monohydroxy acids in slices of porcine thyroid gland
Authors: Odlander Björn , Claesson Hans-Erik
Published: December 2008

Abstract. Slices of porcine thyroid gland were incubated with arachidonic acid and ionophore A 23187. This led to the formation of 5-hydroxy-eicosatetraenoic acid (5-HETE), 12-HETE, 15-HETE and leukotriene B4 (LTB4). Time course studies demonstrated that levels of detected LTB4 reached a plateau after 30 min and that in parallel with the synthesis of this compound, greater amounts of 5-HETE was formed. The present results demonstrate the formation of lipoxygenase products in the porcine thyroid gland, indicating possible physiological/pathophysiological roles for these compounds in this organ.
Annual changes in 6-sulphatoxymelatonin excretion in man
Authors: Bojkowski Christopher J. , Arendt Josephine
Published: December 2008

Abstract: A recently developed RIA for 6-sulphatoxymelatonin, the major urinary metabolite of melatonin, has been used to investigate the annual change in melatonin secretion in humans. Twenty plasma samples were taken from 18 volunteers throughout a 24-h period and simultaneous 6-hourly urine samples were also collected. Plasma melatonin and urinary 6-sulphatoxymelatonin were measured by RIA. 6-Sulphatoxymelatonin assayed in the urine samples was shown to be a good index of the rhythmic characteristics of the plasma melatonin secretion. To study annual changes in excretion four sequential 6-hourly urine samples were collected at monthly intervals from 16 normal volunteers for 13 months. Cosinor curves were fitted to the 6-sulphatoxymelatonin excretion data and the 24-h rhythm was described by the cosinor parameters: amplitude, mesor and acrophase. Significant differences in the acrophase were found during the year. The summer acrophase was phase advanced relative to the winter acrophase by about 1.5 h while intermediate phase positions were observed in spring/autumn. The 24-h excretion of urinary 6-sulphatoxymelatonin was remarkably consistent and there was no annual rhythm. In contrast, the daytime 6-sulphatoxymelatonin excretion between 12.00–18.00 h showed a statistically significant seasonal rhythm, with peaks in December/January and in July.
Which factors predict the results of pituitary surgery in acromegaly?
Authors: Oyen W. J. G. , Pieters G. F. F. M. , Meijer E. , Laarhoven J. v. , Smals A. G. H. , Kloppenborg P. W. C.
Published: December 2008

Abstract. Thirty-one patients with acromegaly who underwent pituitary surgery were investigated for possible predictive factors of the surgical outcome. The patients were divided into two groups: those whose GH levels normalized (<5 μg/l) after operation, group A (N = 18), and those whose GH levels remained elevated, group B (N = 13). There were no differences in age, sex distribution and sellar volume between both groups. There was a tendency to a higher incidence of suprasellar extension of the pituitary tumor in group B (P < 0.10). The basal GH levels in group A (38 ± 5 μg/l) before operation were significantly lower than in group B (100 ± 22 μg/l, P < 0.002). Somatomedin C levels after the operation were significantly lower in group A than in group B (P < 0.05) and were more often in the normal range (P < 0.05). No differences were found in the occurrence of paradoxical GH responses to TRH and/or to GnRH between the groups and neither were there any differences in GH responses to GHRH and to bromocriptine between the groups. The sensitivity to SRIH tended to be higher in group A. After operation, the paradoxical GH response to TRH disappeared in 7 out of 10 patients and to GnRH in 2 out of 5 patients of group A, whereas in group B this anomaly persisted in all 9 after TRH and all 3 patients after GnRH. Hypopituitarism developed in only 5 out of the 31 patients. We conclude that the basal GH level is a factor that to a large extent may predict the effect of pituitary surgery in acromegaly. However, despite normalization of the basal GH level, paradoxical responses to TRH and or GnRH persist in a minority of the cured patients, indicating the presence of remnants of the pituitary adenoma.
Investigations upon the mechanism of inhibition of spermatogenesis in the rat by a dimeric ethynodiol-testosterone ester
Authors: Born Hans-Joachim , Hörster-Poschmann Petra , Stoll Wilfried , Sandow Jürgen , Taubert Hans-Dieter , Kuhl Herbert
Published: December 2008

Abstract. The combination of androgens and progestogens has been shown to be a suitable male contraceptive. Previous experiments revealed that injection of a dimeric testosterone-ethynodiol ester into rats and monkeys induces azoospermia for several weeks. In order to investigate the mechanism of action, we compared the endocrine effects of a single injection of 10 mg of the dimeric ester into intact male rats with that of 6 mg of norethisterone enanthate + 6 mg of testosterone enanthate. After the injection of the dimer there was a transitory reduction of serum FSH and a strong suppression of serum LH and testosterone, of testicular testosterone and of androgen-binding protein (ABP) in the testis and epididymis for at least 8 weeks, whereas spermatogenesis was totally depressed between the 4th and 8th week. Contrary to this, the enanthates caused only a slight suppression of spermatogenesis, although serum LH, testicular testosterone and ABP were profoundly reduced. The only conspicuous difference in the endocrine pattern of both groups during the first 4 weeks was in the serum testosterone level which remained normal in the rats treated with the enanthates. The results suggest that testicular testosterone and ABP concentrations are of minor significance for an intact spermatogenesis, and that some other factors produced by Sertoli cells might be involved and possibly maintained by normal serum testosterone levels.
Substitution therapy of hypogonadal men with transdermal testosterone over one year
Authors: Bals-Pratsch Monika , Langer Klaus , Place Virgil A. , Nieschlag Eberhard
Published: December 2008

Abstract. Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3–5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment. Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.
Biological characterization of charge isomers of human growth hormone
Authors: Skottner A. , Forsman A. , Skoog B. , Kostyo J. L. , Cameron C. M. , Adamafio N. A. , Thorngren K.-G. , Hagerman M.
Published: December 2008

Abstract. Since deamidation of the human GH molecule may alter the manner and extent to which the hormone is cleaved by proteases, and since it has been repeatedly suggested that proteolytic processing is required for the expression of certain of the activities of GH, the present study was conducted to determine whether the biological activity profiles of more acidic forms of human GH are altered. Three charge isomers, GH-b, GH-c and GH-d, representing primarily deamidated forms, were isolated from a native human GH preparation (Crescormon®) in amounts adequate for characterization of their biological activities. All three were essentially equipotent in a radioimmunoassay for human GH. When assessed for growth-promoting activity in the hypophysectomized rat, the isomers were again equipotent with each other and with the GH preparation from which they were derived. The charge isomers also had significant in vitro insulin-like activity on isolated rat adipose tissue and diabetogenic activity in the ob/ob mouse. Thus, the biological activity profiles of these charge isomers of human GH do not differ greatly from one another.
Iodothyronine deiodination in rats with severe non-thyroidal illness
Authors: Grussendorf M. , Wollensack G. , Hüfner M.
Published: December 2008

Abstract. To investigate the iodothyronine metabolism in non-thyroidal illness (NTI), thyroidectomized male Wistar rats bearing the hypercalcemic Walker sarcoma 256 were substituted with, respectively, 2.3 and 11.5 μmol T4/100 g body weight by daily ip injection. Serum T4 and T3 concentrations of euthyroid and hyperthyroid tumor-bearing animals markedly decreased to a nadir at day 8 after tumor implantation: serum T4 fell to, respectively, 43% (euthyroid) and 26% (hyperthyroid) of initial values, serum T3 to 19% (euthyroid) and 26% (hyperthyroid). A measurable serum rT3 concentration could not be detected before and after tumor implantation. In vitro deiodination of T4 to T3 in liver homogenates of the sacrificed animals was not significantly reduced in Walker rats compared with control animals. The activity of T4 deiodinase was significantly induced in hyperthyroid controls (180%) as well as in hyperthyroid Walker rats (155%) in spite of low serum concentrations of T4 and T3. This enzyme induction was even more pronounced in animals whose treatment with high T4 doses was started after tumor implantation. In these rats the serum concentrations of free fatty acids were increased to about 200% of controls. Our data suggest that 1. the fluctuations of iodothyronine serum concentrations in NTI are mainly independent of thyroidal secretion, and 2. the intracellular iodothyronine levels in livers of severely sick animals with different thyroid function are not greatly altered by NTI, in spite of markedly decreased total serum levels.
Changes in serum angiotensin-converting enzyme in acutely starved non-obese patients
Authors: Komaki Gen , Tamai Hajime , Mori Takahiro , Nakagawa Tetsuya , Mori Shu
Published: December 2008

Abstract. We investigated changes in the serum angiotensin-converting enzyme, as an index of thyroid hormone action, before, during and after fasting in 15 non-obese, hospitalized patients. Serum angiotensinconverting enzyme decreased significantly from 14.6 ± 1.1 U/l before fasting to 13.2 ± 1.1 U/l on the 5th day (P < 0.05, N = 15) during fasting, and to 10.6 ± 1.0 U/l on the 10th day (P < 0.05, N = 8). The serum TSH and T3 levels decreased significantly to below the normal range, and the serum T4 level decreased gradually during fasting, whereas free T4 (Amerlex) changed slightly, but within normal range. Although re-feeding did not lead to any reduction in the serum TSH, T3, or T4 level, the serum angiotensin-converting enzyme further decreased to 8.7 ± 0.9 U/l on the 5th day of re-feeding compared with that on the 10th day of fasting (P < 0.01, N = 8). There was a delay in the re-elevation of serum angiotensin-converting enzyme following a rise in serum T3. No correlations were found between serum angiotensin-converting enzyme levels and thyroid hormone levels throughout the study period. It is concluded that a significant reduction in the serum angiotensin-converting enzyme level occurs under a 'low T3' state during acute starvation, although there is no clear association between serum angiotensinconverting enzyme and thyroid hormone levels.
Effects of plasma volume and osmolality on secretion of atrial natriuretic peptide and vasopressin in man
Authors: Kamoi Kyuzi , Sato Fujio , Arai Okuhiro , Ishibashi Miyuki , Yamaji Tohru
Published: December 2008

Abstract. To clarify the role of blood volume and osmolality in the mediation of the release of atrial natriuretic peptide (ANP) and to examine the relationship between plasma ANP and plasma AVP levels in man, the effects of hypertonic saline and hypertonic mannitol infusion, and of water load on plasma levels of ANP and AVP were studied. Infusion of 5% saline to 7 healthy men at a rate of 0.05 ml min−1·kg−1 for 2 h resulted in a parallel rise in plasma sodium, osmolality, plasma ANP and plasma AVP, indicating that plasma hyperosmolality stimulates secretion of both ANP and AVP. Infusion of 20% mannitol to 6 healthy men at the same rate resulted in a parallel increase in plasma osmolality, plasma ANP and AVP, whereas plasma sodium decreased, indicating that plasma hyperosmolality stimulates secretion of both ANP and AVP. Water load (20 ml/kg) into 7 healthy men produced a prompt and parallel fall in plasma sodium, plasma osmolality and plasma AVP. In contrast, plasma ANP and plasma volume, calculated from the changes in hematocrit, increased concomitantly, which indicates that expanded plasma volume stimulates secretion of plasma ANP. These results suggest that secretion of ANP in man is regulated principally by plasma volume, which may be modulated by a change in plasma osmolality. AVP secretion, on the other hand, is controlled mainly by osmotic change and secondarily by plasma volume.