bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological levels of immunoreactive ANH-like peptides in human follicular fluid
Authors: Sundsfjord J. A. , Forsdahl F. , Thibault G.
Published: December 2008

The concentrations of immunoreactive C-terminal (ANH-(99-126)) and N-terminal (ANH-(1-98)) portions of pro-ANH were measured in follicular fluid and plasma samples from 9 young women undergoing in vitro fertilization. ANH-(99-126) and ANH-(1-98)-like immunoreactivity levels in plasma were 6.0–25.4 (mean 12.2) pmol/1 and 184–427 (mean 300) pmol/1, respectively, whereas the corresponding levels in follicular fluid were 3.8–8.0 (mean 4.9) pmol/1 and 169–385 (mean 262) pmol/1. The concentrations of both ANH-like peptides were consistently lower (p < 0.01) in the follicular fluid than in the matched plasma samples, but within the variation found in plasma controls. It is concluded that ANH-like peptides in the follicular fluid, whether secreted locally or derived from circulating ANH, might play a physiological role in the biosynthesis of ovarian steroid hormones or follicular maturation and fluid dynamics.
Serum GH binding protein activities identifies the heterozygous carriers for Laron type dwarfism
Authors: Laron Z. , Klinger B. , Erster B. , Silbergeld A.
Published: December 2008

Measurement of GH-binding protein activity and IGF-I was carried out in the sera of 13 patients with Laron type dwarfism, a syndrome caused by a lack of GH receptors which leads to impairment of IGF-I generation, and those of 16 of their close relatives. GH binding protein activity was measured by incubating 125I-hGH with 100 μl serum in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 125I-hGH binding protein complexes from free 125I-hGH by gel filtration. The results are expressed as percent specific binding relative to an adult reference serum. IGF-I was determined by RIA after acid extraction on octadecylsilane silica columns. All Laron type dwarfism patients had no, or only negligible GH binding protein activity, which supports the evidence that serum GH binding protein corresponds to the extracellular domain of the membranal GH receptor. Eight of the 16 relatives had serum GH binding protein activity more than 2 sd below the mean for age, a finding considered to denote heterozygocity for their molecular defect disease. The significant correlation (p < 0.001) between serum GH binding protein activity and IGF-I levels supports this conclusion. The ability to define heterozygotes of Laron type dwarfism will be helpful in genetic counselling.
Discordant immune and growth response to pituitary and biosynthetic growth hormone in siblings with isolated growth hormone deficiency type IA
Authors: Hauffa Berthold P. , Illig Ruth , Torresani Toni , Stolecke Herbert , Phillips John A.
Published: December 2008

Two brothers with familial isolated growth hormone deficiency type IA homozygous for the same 6.7 kb deletion on chromosome 17 including the growth hormone gene were intermittently treated with various forms of hGH for more than 7 years. While the elder brother (Patient 1) showed a good growth response to pituitary hGH, the younger one (Patient 2) developed high titre growth blocking hGH antibodies early in the course of treatment and grew only 2.2–3.9 cm/year on a hGH dose of 12–26 IU/m2 per week. When the younger brother was changed to a higher dose (33 IU/m2 per week) of biosynthetic methionyl hGH he had striking catch-up growth and he has subsequently maintained a height velocity of 10.0 cm/year for the last 2 years. During this time his antibody titres have decreased over 1000-fold. These findings demonstrate that therapy with biosynthetic methionyl hGH may provide an effective form of treatment for subjects with isolated growth hormone deficiency type IA who do not grow in response to native hGH, and imply that biosynthetic methionyl hGH may be less antigenic than pituitary derived hGH.
Effects of lithium on stimulated metabolic parameters in dog thyroid slices
Authors: Tseng Fen-Yu , Pasquali Daniela , Field James B.
Published: December 2008

Thyroid abnormalities may develop during chronic lithium therapy for affective disorders. Lithium, like iodide, inhibits TSH stimulation of adenylate cyclase and thyroid hormone release. The present study examined the effect of lithium on stimulation of intrathyroidal intermediary metabolism by several agonists. LiCl (5 mmol/l) did not inhibit basal cAMP, glucose oxidation or 32P incorporation into phospholipids in dog thyroid slices. Although LiCl inhibited TSH stimulation of cAMP, it did not abolish the hormone's effect on cAMP-dependent protein kinase. The stimulation of iodide organification, glucose oxidation or 32P incorporation into phospholipids by TSH, carbachol and phorbol esters was not inhibited by lithium. This is in contrast to the effects of iodide, which inhibited stimulation of glucose oxidation and 32P incorporation into phospholipids by various agonists. Thus, although both lithium and iodide inhibited TSH-stimulated cAMP formation, they act differently on intrathyroidal intermediary metabolism.
High and low doses of luteinizing hormone induce different changes in testicular microcirculation
Authors: Widmark Anders , Damber Jan-Erik , Bergh Anders
Published: December 2008

To study the effects of LH on total testicular blood flow and microcirculation, rats were treated with 2.5 or 25 μg LH sc and measurements were made on control rats and on LH-treated rats 1, 2, 3, 4, 6 and 12 h, after treatment. After treatment with 25 μg LH, total testicular blood flow, as measured with the radioactive microsphere method, was decreased at 6 h and increased at 12 h. Testicular microcirculatory blood flow was recorded with laser Doppler flowmetry and regular oscillations in blood flow, vasomotion, was observed in control rats. Vasomotion was not present 4 and 6 h after treatment with 25 μg LH, but returned at 12 h. Prior to and concomitantly with these changes in vasomotion, polymorphonuclear leukocytes accumulated in testicular microvessels and migrated into the interstitial tissue. These changes were followed, 6 h after treatment, by an increased vascular permeability, measured as increased testicular interstitial fluid volume. The lower dose of LH (2.5 μg), doubled plasma testosterone concentration and initially decreased interstitial fluid volume, and later induced a slight increase in blood vessel leukocytes. At the times studied, no changes could be observed in the other vascular parameters. In conclusion, it is suggested that LH, probably via some Leydig cell product, promotes regulatory effects on testicular microcirculation, but different magnitudes of LH stimulation induce different responses.
Pharmacokinetics of 3,5,3'-triiodothyroacetic acid and its effects on serum TSH levels
Authors: Menegay C. , Juge C. , Burger A. G.
Published: December 2008

3,5,3'-triiodothyroacetic acid is an effective inhibitor of TSH secretion in central hyperthyroidism. Serum 3,5,3'-triiodothyroacetic acid was measured with an RIA preceded by immunoprecipitation. An anti-3,5,3'-triiodothyroacetic acid antibody was obtained in rabbits, using 3,5,3'-triiodothyroacetic acid coupled to hemocyanin and diazotized benzidine as antigen (crossreactivity with T4, T3, tetraiodothyroacetic acid was 0.2, 1.1, and 5%, respectively). Endogenous 3,5,3'-triiodothyroacetic acid levels could not be detected in 14 euthyroid, 10 hypothyroid and 10 hyperthyroid sera (detection limit 0.055 nmol/l). Kinetic studies were performed in 6 healthy male subjects who received an oral and an iv dose of 1050 μg of 3,5,3'-triiodothyroacetic acid. The serum measurements were analysed according to a non-compartmental method. The half-life of 3,5,3'-triiodothyroacetic acid was 6 h 22 min ± 29 min, the volume of distribution was 114 ± 9 1/70 kg, and the plasma clearance rate was 298 ± 14 1 · (70 kg)−1 · day−1. Highest 3,5,3'-triiodothyroacetic acid levels were measured after 40 min (for T3 2–3 h) and its absorption was 67±6%. The nadir of the mean TSH levels was 0.72 ± 0.09 mU/l 6 h after 3,5,3'-triiodothyroacetic acid administration. However, the time course of serum TSH response did not differ from that obtained after administration of 37.5 μg T3. The dose-response effect for TSH was studied using oral doses of 350, 700, 1400 and 2800 μg 3,5,3'-triiodothyroacetic acid. TSH was measured 9 h after 3,5,3'-triiodothyroacetic acid administration at 17.00 h, and compared with control serum TSH levels obtained at 08.00 h (1.53 ± 0.11) and at 17.00 h the day before the test (1.87 ± 0.11). They were 1.05 ± 0.15 (N = 9, mean ± sem), 0.83 ± 0.08 (N = 24), 0.66 ± 0.06 (N = 24), and 0.43 ± 0.02 mU/l (N = 6), respectively. In conclusion, TSH inhibition by 3,5,3'-triiodothyroacetic acid is similar to T3, with a potency ratio of 1 to 18.
The prognostic value of TSH receptor binding and thyroid stimulating antibodies following antithyroid drug treatment of Graves' disease
Authors: Wilson R. , Fraser W. D. , McKillop J. H. , Thomson J. A.
Published: December 2008

Following a course of medical therapy for Graves' disease approximately 50% of patients relapse. Previous studies have tried to identify these patients by measuring antibodies to the TSH receptor using a range of assay methods. Such studies have produced widely discrepant results. The aim of the present study was to compare the accuracy with which TSH receptor binding antibodies and thyroid-stimulating antibodies could identify cases of relapse and remission. Fifty-six newly diagnosed and previously untreated Graves' disease patients were recruited into the study. At presentation 4 were negative for TSH receptor antibody and 5 negative for TS-ab. The remaining 47 were positive for TSH receptor antibody and TS-ab although correlation of the degree of abnormality between methods was poor (r = 0.13 NS). After 12 months carbimazole treatment 28 patients relapsed during the following year and 19 remained in remission. TSH receptor antibody levels obtained at the end of a 12-month course of treatment correctly identified 93% who relapsed and 95% who remained in remission. TS-ab levels could only correctly identify 68% who relapsed and 53% who remained in remission. These results have shown that the accuracy with which patients likely to relapse can be identified depends on the assay method chosen which may account for some of the discrepancies found in previously published studies.
Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement
Authors: Sturgess Ian , Thomas Simon H. , Pennell Dudley J. , Mitchell Derek , Croft Desmond N.
Published: December 2008

Eleven patients with treated hypothyroidism were investigated to examine the effects of time on their thyroid function tests. Each patient was clinically and biochemically euthyroid on once daily thyroxine replacement therapy, taken in the morning. TSH followed a diurnal rhythm with a peak level at 23.30 h and a trough level at 14.30 h. Four subjects had TSH trough levels within the normal range, but with peak levels outside this range. FT4 and FT3 levels fell from their highest levels some three hours after ingestion to the lowest levels just prior to the next dose. This study shows that there are significant time-related variabilities in TSH and thyroid hormone levels in treated hypothyroid patients. This should be taken into account when interpreting results of their thyroid function tests.
Single-dose response study of the somatostatin analogue octreotide in acromegaly
Authors: van Liessum Peter A. , Pieters Gerlach F. , Smals Anthony G. , Hermus Ad R. , Benraad TheoJ. , Kloppenborg Peter W.
Published: December 2008

The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 μg daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 μg octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 μg. The 400 μg octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 μg/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 μg than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 μg injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 μg octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 μg octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 μg doses are superior to 25 μg, but do not differ from each other.
Partial loss of responsiveness of human fetal pituitary cells to hGHRH after chronic exposure
Authors: Blumenfeld Zeev , Tapaneinen Paivi , Kaplan Selna L. , Grumbach Melvin M. , Jaffe Robert B.
Published: December 2008

Synthetic hGHRH was incubated with dispersed pituitary cells from 14 human fetuses at 14–23 weeks of fetal age. After at least three days following plating the cells on an extracellular matrix in serum-containing medium, 3 h incubation with hGHRH in serum-free medium induced a significant increase in GH secretion into the medium at concentrations of hGHRH of 0.01 nmol/1 or higher. After 24 h exposure to 0.5 nmol/1 hGHRH, subsequent incubation with 0.5 nmol/1 hGHRH for 3 h induced significantly lower GH secretion into the medium compared to the GH secretion by cells exposed previously to medium alone. In contrast, when the subsequent exposure to hGHRH was at 10-fold higher concentrations than the concentration present in the initial exposure, GH secretion into the medium did not significantly decrease compared to previously untreated cells. These results suggest that desensitization (down-regulation) of GHRH receptors on somatotropes may be involved in the mechanism by which prior GHRH exposure inhibits GH secretion in response to subsequent GHRH administration. Such desensitization seems to occur in the human fetus but is incomplete. The desensitization may be overcome by increasing the GHRH concentrations with subsequent exposure, suggesting that cellular GH depletion is not responsible for the decreased responsiveness observed.
Immunocytochemical localization of the sex hormone-binding globulin in a human hepatoma cell line
Authors: Luppa P. , Oettrich K. , Schwab I. , Langmandel U. , Neumeier D.
Published: December 2008

The human hepatoma cell line HEP G2 was investigated in an indirect immunofluorescence study for localization of the sex hormone-binding globulin. Cells were grown directly to confluency on the slides used for the immunocytochemical staining. A fine granular cytoplasmatic fluorescence pattern revealed the presence of sex hormone-binding globulin. Chang-liver cells used as controls, incubated under the same conditions, did not fluoresce. The synthesis of the hormone-binding protein in HEP G2 cells, which could be stimulated by L-thyroxine in the culture medium, was monitored by either indirect immunofluorescence or by immunoradiometric determination of sex hormone-binding globulin in the supernatant. These studies demonstrate that immunofluorescence techniques are able to detect sex hormone-binding globulin in human hepatoma cells.
A case of normotensive primary aldosteronism with hypopituitarism, epilepsy, and medullary sponge kidney
Authors: Kuroda Takeo , Okamura Ken , Yoshinari Mototaka , Ikenoue Hiroshi , Sato Kaori , Yamashita Yoshiaki , Takishita Shuichi , Fujishima Masatoshi
Published: December 2008

A 55-year-old man with normotensive primary aldosteronism, hypopituitarism, epilepsy, and medullary sponge kidney is reported. Seventeen years before admission, he had been noted to have hypokalemia associated with high potassium clearance, suppressed plasma renin activity, metabolic alkalosis, and normal blood pressure as well as low urinary excretion of 17-hydroxycorticosteroids. He kept normotensive in spite of hyperaldosteronism until nine months after the initiation of replacement therapy with glucocorticoid and thyroxine for hypopituitarism, when he became hypertensive. Hypopituitarism seemed to play a role in keeping a normal blood pressure despite long-standing hyperaldosteronism.
Diagnostic value of bioactive FSH in male infertility
Authors: Jockenhövel Friedrich , Khan Shafiq A. , Nieschlag Eberhard
Published: December 2008

Bioactive FSH and immunoreactive FSH were determined in 193 infertile men and in 23 men with proven fertility using the Sertoli cell aromatase bioassay for bioactive FSH measurement and a two-site fluoroimmunoassay for immunoreactive FSH measurement. Overall bioactive and immunoreactive FSH levels correlated well (r = 0.74, p < 0.001) but were significantly different from fertile men (bioactive FSH: 6.2 ± 0.3 U/l; immunoreactive FSH: 4.1 ± 0.4 U/l) in patients with Klinefelter's syndrome (24.1 ± 6.1; 26.9 ± 3.0), non-obstructive azoospermia (25.1 ± 4.3; 22.2 ± 4.0), maldescended testes (12.5 ± 4.6; 14.6 ± 1.6), and patients with severe oligozoospermia (11.9 ± 1.2; 11.2 ± 1.0). Infertile men with moderate oligozoospermia (8.9 ± 1.5; 8.0 ± 1.1) and normal sperm counts (9.6 ± 1.1; 7.6 ± 1.0) had insignificantly elevated bioactive FSH and immunoreactive FSH levels. Bioactive to immunoreactive FSH ratios were significantly reduced in all patient groups except for patients with normal sperm counts when compared with fertile men. A considerable number of patients exhibited elevated immunoreactive FSH concomitant with normal bioactive FSH levels. We conclude that 1. determination of immunoreactive FSH suffices for classification of patients; 2. bioactive to immunoreactive FSH ratios are reduced in infertile men; 3. some men might secrete immunoreactive FSH with reduced bioactivity.
Decreased anterior pituitary T3 nuclear receptors in a Walker 256 carcinoma-bearing rat model of nonthyroidal disease
Authors: Hupart Kenneth H. , DeFesi Charles R. , Katz Claire P. , Shapiro Lawrence E. , Surks Martin I.
Published: December 2008

Rats bearing the Walker 256 carcinoma have decreased pituitary nuclear T3 but normal pituitary TSH content and response to experimental hypothyroidism. To elucidate further the role of T3 receptor occupancy and biological response in the tumor-bearing rat model of nonthyroidal disease, we measured the concentration of T3 nuclear receptors, rTSH and rGH and β-TSH mRNA and GH mRNA in the anterior pituitary of euthyroid rats bearing the Walker 256 carcinoma. The abundance of T3 nuclear receptors was decreased in tumorbearing rats and was associated with a decrease in mRNA content for β-TSH and GH. α-tubulin mRNA was decreased to a comparable degree. The pituitary content of rTSH and rGH was, however, the same as in control animals. Since tumor rats have normal regulation of TSH secretion by thyroid hormone, the present findings suggest that TSH secretion in T rats is maintained by a lower T3 nuclear receptor occupancy than in controls. The decrease in β-TSH mRNA may precede a decrease in TSH synthesis and changes in pituitary TSH stores. Since the decrease in GH mRNA was comparable to the decrease in α-tubulin mRNA, it does not appear to be specifically related to decreased T3 nuclear receptor occupancy. We conclude that, in the tumor-bearing rat model of nonthyroidal disease, decreases in β-TSH mRNA occur despite a decreased T3 receptor occupancy. Both thyroid-dependent and thyroid-independent factors may be involved in regulating β-TSH mRNA.
Effect of GnRH agonists on the thymus in female rats
Authors: Ataya Khalid M. , Sakr Wael , Blacker Charla M. , Mutchnick Milton G. , Latif Zuhair A.
Published: December 2008

The potential clinical applications of GnRH agonists are growing. We studied the effects of two GnRH agonists on the adult female rat thymus in 4 experiments. GnRH agonists administered sc and continuously significantly increased wet and dry thymic weights (absolute and relative). Thymic enlargement was related to the duration of treatment with GnRH agonists. The maximum increase in thymic weight occurred at approximately 18 days following initiation of treatment with GnRH agonists. Thymic enlargement does not appear to involve enhanced mitotic activity as measured by incorporation of tritiated thymidine into thymic tissue and thymic DNA. Histologic examination and computer-assisted morphometric analysis of thymuses indicated an increase in cortex to medulla ratio most pronounced at 10 and 18 days of GnRH agonist treatment. No consistent increases in splenic weight or bone marrow cell counts were observed. Thymosin alpha-1 but not thymosin beta-4 increased in GnRH agonist-treated rats. Thymic weight correlated negatively with ovarian and uterine weights, relative adrenal weight, serum estradiol, LH, and positively with thymosin alpha-1. Exogenous estrogen administration reversed GnRH agonist-induced thymic weight increase. Whether GnRH agonists have direct thymic effects remains to be determined.
Relationship of nocturnal plasma bioactive and immunoactive ACTH concentrations to cortisol secretion in normal men
Authors: Poland Russell E. , Hanada Koichi , Rubin Robert T.
Published: December 2008

Plasma concentrations of ACTH and cortisol were measured at 15-min intervals from 22.30 to 07.00 h in 8 normal male volunteers. ACTH was measured both by a modified and sensitized isolated adrenal cell bioassay and by radioimmunoassay. Within-subject correlations between bioactive ACTH and cortisol concentrations ranged between 0.86 and 0.95, with an average correlation of 0.93 (86% shared variance). In contrast, within-subject correlations between immunoassayable ACTH and cortisol ranged between 0.03 and 0.92, with an average correlation of 0.69 (48% shared variance). These results suggest that plasma ACTH concentrations determined by RIA might not accurately reflect the capacity of plasma to regulate the secretion of adrenal glucocorticoids.
Ciamexone in endocrine orbitopathy A randomized double-blind, placebo-controlled study
Authors: Kahaly G. , Lieb W. , Müller-Forell W. , Mainberger M. , Beyer J. , Vollmar J. , Staiger Ch.
Published: December 2008

The influence of ciamexone on the activity and course of endocrine orbitopathy was investigated. Fifty-one patients with active orbitopathy classes II-VI were allocated randomly to two groups: over a period of six months, 26 patients received 300 mg/day ciamexone and 25 patients received placebo tablets. In both groups, prednisolone was administered in addition in the first four weeks. Ophthalmological investigations and clinical tests as well as orbit sonography were carried out before as well as one, three and six months after the beginning of therapy. Before and after treatment, computer tomography of the orbit was performed. Symptoms and signs did not show any significant improvement one and six months after therapy. No differences between the two therapy groups were observed. Detailed examination did not reveal any preferential action of the product on individual parameters. Sonography and computer tomography showed no significant alterations of the thickness of the oculomotor muscles. Thus administration of 300 mg ciamexone once a day as compared with placebo did not show any effect on the course and activity of endocrine orbitopathy.
Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women
Authors: Boesgaard Søren , Hagen Claus , Andersen Anders Nyboe , Fenger Mogens , Eldrup Ebbe
Published: December 2008

The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women received 5-h infusions of either glucose (N = 6) or dopamine at rates of 0.04 (N = 6), 0.4 (N = 6) and 4.0 μg · kg−1· min−1 (N = 8). After 3 h, 10 mg metoclopramide was given iv. No intergroup differences regarding ACTH and cortisol levels were observed (p>0.05). In a second study six women received dopamine (4.0 μg·kg−1·min−1) or glucose for 18 h. During the infusions cortisol and ACTH levels were similar on the two study days. Administration of metoclopramide (10 mg) after 17 h induced a significant increase in cortisol levels during dopamine infusion (p<0.05), whereas no effect was observed during placebo infusion. ACTH levels were unaffected by metoclopramide. In a third study, 9 normal women and 9 normal men received fenoldopam (0.5 μg·kg −1·min−) or placebo infusions for 3 h. In males, median ACTH and cortisol levels were significantly lower (p<0.05) during fenoldopam compared with placebo infusion. In contrast, fenoldopam did not affect ACTH and cortisol levels in normal women. The results suggest that the effect of dopamine D-1 receptor stimulation on ACTH and cortisol secretion is mainly at the hypothalamic level and that this effect is sex-dependent. In addition, we hypothesize that raised dopaminergic activity for a prolonged period of time may have an inhibitory effect on the hypothalamic-pituitary-adrenal axis. This may be triggered by low estrogen levels.
Failure of pyridostigmine to increase both basal and GHRH-induced GH secretion in the night
Authors: Ghigo E. , Arvat E. , Mazza E. , Mondardini A. , Cappa M. , Müller E. E. , Cammani F.
Published: December 2008

The aim of this study was to verify that the stimulatory effect of cholinergic agonists on both basal and stimulated GH release observed in the morning persists in the night. The effects of pyridostigmine (120 mg orally), a cholinesterase inhibitor, on both basal and GHRH (1 μg/kg iv) - induced GH secretion were studied in 8 healthy volunteers, aged 22-30 years. In the morning, administration of pyridostigmine induced a significant increase in basal GH levels compared with saline (area under the response curve, mean ± SEM: 277.0 ± 54.0 vs 49.7 ± 8.2 μg·l−1·h−1, p < 0.02) as well as a strong potentiation of the GHRH-induced GH release (2117.6 ± 353.0 vs 427.9 ± 87.0 μg·l−1·h−1, p < 0.02). In the night, GH secretion after pyridostigmine did not differ from saline (194.5 ± 21.9 vs 89.4 ± 28.7 μg·l−1·h−1). Moreover pyridostigmine failed to potentiate the GHRH-induced GH increase (1071.9 ± 170.4 vs 740.2 ± 150.9 μg·l−1·h−1). The pyridostigmine + GHRH-induced GH rise during the night was lower (p < 0.05) than in the morning. All together, these data seem to indicate that cholinergic neurons controlling GH secretion are already maximally stimulated at night. As cholinergic activity negatively modulates SRIH secretion, our findings suggest that a reduced somatostatinergic tone in the hypothalamus is present during the night.
Effect of oral clonidine, insulin-induced hypoglycemia and exercise on plasma GHRH levels in short-stature children
Authors: Gil-Ad I. , Leibowitch N. , Josefsberg Z. , Wasserman M. , Laron Z.
Published: December 2008

Human growth hormone release is affected by a variety of pharmacological and physiological stimuli. We have studied the effect of oral clonidine, insulin hypoglycemia, and exercise on plasma hGH and GHRH levels in 31 healthy short-stature children. Thirteen underwent an oral clonidine test (0.15 mg/m2), 12 an iv. insulin test (0.1 U/kg), and 6 performed exercise (running for 10 min in a defined route). GHRH-1-44 was extracted from plasma on silica columns and determined by RIA. Although all three stimuli induced a marked increase in plasma hGH levels, only clonidine induced a significant increase in plasma GHRH levels. Maximal increment in GHRH during clonidine was 6.82 ± 1.05 pmol/l (mean ± SEM) as compared with 0.51 ± 0.28 and 0.53 ± 0.62 during hypoglycemia and exercise (p<0.0005 and p<0.005), respectively. An additional 24 subjects received TRH 0.2 mg/kg iv: 8 TRH alone, 8 TRH and insulin, and 8 TRH and clonidine. Only insulin potentiated the TRH-induced TSH response with a peak of 22.0 ± 3.2 vs 16.0 ± 0.8 and 15.3 ± 1.5 mU/l (p<0.025) for TRH alone and TRH and clonidine, respectively. It is suggested that clonidine stimulates hGH secretion mainly through an enhancement of GHRH release, whereas stress stimuli such as hypoglycemia and exercise achieve hGH release by a different mechanism, possibly inhibition of somatostatin.
Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta)
Authors: Fingscheidt Ulrich , Weinbauer Gerhard F. , Khan Shafiq A. , Nieschlag Eberhard
Published: December 2008

Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.
In vitro modulation of porcine Leydig cell steroidogenesis by phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol
Authors: French Joseph T. , Welsh Thomas H.
Published: December 2008

Serum-free primary cultures of neonatal (1-day-old) porcine Leydig cells were used to study the effects of phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol on testosterone and pregnenolone production. Phorbol-12-myristate-13-acetate alone from 0.001-10 μmol/l stimulated testosterone and pregnenolone production, whereas 1,2-dioctanoylglycerol alone had no effect on steroid production, relative to control. Phorbol12-myristate-13-acetate and 1,2-dioctanoylglycerol each inhibited pLH-stimulated testosterone and pregnenolone production. To further clarify the influence of these protein kinase C activators on steroidogenesis, cultured Leydig cells were treated with either phorbol-12-myristate-13-acetate or 1,2-dioctanoylglycerol plus forskolin (an adenylate cyclase activator). Both phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol inhibited forskolin-stimulated testosterone production. Phorbol-12-myristate-13-acetate had no effect on forskolin-stimulated pregnenolone production and only the highest concentration of 1,2-dioctanoylglycerol (100 μmol/l) inhibited forskolin-stimulated production of pregnenolone. These data demonstrate that porcine Leydig cell steroidogenesis can be modulated by interactions of the protein kinase C and protein kinase A second messenger systems.
Recovery of the thyroid function in patients with atrophic hypothyroidism and blocking type TSH binding inhibitor immunoglobulin
Authors: Okamura Ken , Sato Kaori , Yoshinari Mototaka , Ikenoue Hiroshi , Kuroda Takeo , Nakagawa Mizuho , Tsuji Hiroshi , Washio Masakazu , Fujishima Masatoshi
Published: December 2008

The prognosis of atrophic hypothyroidism with blocking type TSH-binding inhibitor immunoglobulin was studied. Among 45 patients (16 males and 29 females) with overt hypothyroidism (serum TSH >40 mU/l) without goitre, thyroid autoantibody to microsomal antigen was positive in 38 or 84.4%, and 4 or 8.9% had TSH-binding inhibitor immunoglobulin, which was shown to be a TSH-stimulation blocking antibody by cAMP production assay using cultured porcine thyroid cells. Thyroidal radioactive iodine uptake was low and thyroid hormone replacement therapy was required. Long-term follow up of 2 patients with strongly positive TSH-binding inhibitor immunoglobulin for 2 to 7 years, however, revealed recovery of the thyroid function after steroid therapy or spontaneously with iodide restriction, respectively, correlating with decrease in both TSH-binding inhibitor immunoglobulin and TSH-stimulation blocking antibody activities. Thyroidal radioactive iodine uptake became normal and histological examination of the thyroid in one patient revealed well-preserved thyroid follicles with lymphocytic infiltration. Recovery of thyroid function can be expected with a decrease in TSH-binding inhibitor immunoglobulin activity in atrophic hypothyroidism, which is not necessarily the end stage of chronic thyroiditis.
Effect of adrenalectomy at different pregnancy stages on maternal and fetal serum corticosteroid binding globulin and corticosterone in the rat
Authors: Cohen Alia , Savu Lia , Vranckx Roger , Maya Michelle , Nunez Emmanuel A.
Published: December 2008

The response of pregnant rat corticosteroid binding globulin to maternal adrenalectomy was studied as a function of the stage of pregnancy. Non-pregnant or pregnant rats were deprived of their adrenal glands during 4 days. In non-pregnant animals, adrenalectomy led to undetectable corticosterone levels and to the doubling of corticosteroid binding globulin. In pregnant rats adrenalectomized at 12 days and studied at 16 days, the serum corticosterone was likewise undetectable and the corticosteroid binding globulin was doubled as compared with pregnant rats of the corresponding age. In contrast, adrenalectomy from day 14 to 18 or from day 16 to 20 did not deplete the maternal serum corticosterone and the corticosteroid binding globulin remained unchanged. Under these conditions neither fetal corticosteroid binding globulin nor fetal corticosterone were modified. However, when the pregnant rats adrenalectomized from day 16 to 20 also received an injection of 30 mg of metyrapone on days 19 and 20 in order to inhibit fetal adrenal secretion, the maternal response was again a depletion of serum corticosterone together with an increase in corticosteroid binding globulin. Under these conditions, the fetus also reacted by a fall of corticosterone and a rise of corticosteroid binding globulin. Our results suggest that the maternal response of corticosteroid binding globulin to adrenalectomy depends on the pregnancy stage inasmuch as it may be influenced by a supply of corticosterone from the fetus during late pregnancy. Moreover, they show that in this late period, fetal corticosteroid binding globulin is regulated independently.
Progesterone regulation of prolactin release from human endometrial stromal cells in culture: Potential bioassay for progestational activity
Authors: Casslén Bertil G. , Siler-Khodr Theresa M. , Harper Michael J. K.
Published: December 2008

Prolactin was produced by endometrial stromal cells, but not by epithelial cells, in primary culture. Production was stimulated by progesterone in a time and dose (1–1000 nmol/1) dependent way. Stimulation was started one day after plating. The release of prolactin started one day earlier in cultures from luteal phase than proliferative phase endometria. The responsiveness to progesterone declined with time in culture, sooner in luteal than in proliferative phase cultures, but could, at least partly, be maintained by including estradiol (10 nmol/l) in the medium. Lost response to progesterone could be restored by stimulation with estradiol for two days. The results indicate that prolactin synthesis in the endometrium is regulated directly by progesterone, and indirectly by estradiol. We suggest that prolactin production in primary stromal cell cultures could serve as a bioassay for progestational activity of steroid hormones in the human endometrium.
Vasopressin enhances the clearance of β-endorphin immunoreactivity from rat cerebrospinal fluid
Authors: Sweep C. G. J. , Boomkamp Margreet D. , Barna István , Logtenberg A. Willeke , Wiegant Victor M.
Published: December 2008

The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of β-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4–9) (1.44 fmol), Nα-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of β-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1–9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied β-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel β-endorphin-(1–31), the β-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lifes of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol β-endorphin-(1–31)) significantly enhanced the disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of β-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain.
Acute effects of cortisone acetate on growth hormone response to growth hormone-releasing hormone in normal adult subjects
Authors: Giustina Andrea , Doga Mauro , Bodini Corrado , Girelli Angela , Legati Fabio , Bossoni Simonetta , Romanelli Giuseppe
Published: December 2008

Glucocorticoids have been shown to inhibit GH secretion in normal man when administered in large amounts for several days. The aim of our study was 1. to investigate the acute effects of a single dose of glucocorticoids on GH secretion in normal man; 2. to look at the relationship between the increase in serum cortisol concentration and GH response to the stimuli. Six healthy volunteers received on three occasions in random order an iv injection of GHRH (1–29) NH2, 100 μg, alone or 60 min after oral administration of either 25 or 50 mg of cortisone acetate. Mean stimulated GH levels, GH peak and integrated GH concentration were significantly lower after GHRH plus cortisone 25 mg than after GHRH alone. Mean GH levels at 15 and 30 min after GHRH injection and the peak GH level showed a further decrease after GHRH plus cortisone 50 mg. We conclude that acute administration of pharmacological doses of glucocorticoids is able to inhibit GH response to GHRH, probably through enhancement of endogenous somatostatin release. Moreover, this pharmacological effect of glucocorticoids seems to be dose-dependent and thus directly related to serum cortisol concentrations.
Internalization of calcitonin receptors in primary rat kidney cell cultures
Authors: Schneider H.-G. , Raue F. , Bollenbach N. , Scherübl H. , Ziegler R.
Published: December 2008

Cultured rat kidney cells possess specific calcitonin receptors and a calcitonin-responsive adenylate cyclase. At 37°C bound 125I-salmon calcitonin becomes increasingly resistant to acid washing. If 125I-salmon calcitonin is removed from the medium after binding, bound hormone decreases over the next 5 h. Monensin, which blocks lysosomal processing, inhibits the decrease of bound hormone. These data indicate that calcitonin receptors are internalized after binding of hormone in kidney cells. Cycloheximide prevents internalization, when it is administered 4 h before 125I-salmon calcitonin binding is studied. Pre-incubation of the cells with 10−7 mol/l unlabelled salmon calcitonin decreases specific binding; recovery of binding needs 48 h to occur. The long time interval for recovery makes it unlikely that calcitonin receptors recycle. This is the first demonstration that normal rat kidney cells internalize calcitonin after binding. It might contribute to the loss of calcitonin bioactivity which is seen after continuous administration.
Erythropoiesis, serum erythropoietin, and serum IGF-I in rats during accelerated growth
Authors: Kurtz Armin , Matter Robert , Eckardt Kai-Uwe , Zapf Jürgen
Published: December 2008

In this study we have examined the correlation between activity of erythropoiesis and serum concentrations of erythropoietin and insulin-like growth factor I in male and female rats during accelerated growth (day 30-90). We found that fractional incorporation of iron into newly formed red blood cells was linearily correlated with body weight gain. Total iron incorporation into newly formed red blood cells reflecting total daily red cell formation increased almost linearily between day 25 and 80 after birth in both sexes. While serum erythropoietin concentrations decreased in the time interval investigated (25–120 days), serum IGF-I levels increased in both sexes between day 25 and 55. In this period, individual values of total iron incorporation into red blood cells and serum IGF-I concentrations were linearily correlated. Our observations support the concept that IGF-I rather than erythropoietin modulates erythropoiesis during accelerated growth and thus manages a proportional increase in body mass and oxygen transport capacity.
Biphasic response of rat tibial growth to thyroxine administration
Authors: Ren Song Guang , Huang Ze , Sweet Donald E. , Malozowski Saul , Cassorla Fernando
Published: December 2008

To evaluate the dose-response relationship between thyroxine and tibial growth, 60 male rats age 21 days were rendered hypothyroid by administration of methimazole in the drinking water. Twenty-one days later, the hypothyroid rats were randomly divided into 5 groups which received 0, 2, 8, 32, or 64 μg·kg−1·day−1 of T4 im for 21 days. All animals were sacrificed at age 64 days. Rat tibia were removed for measurement of epiphyseal growth plate width and longitudinal growth rate. Serum T4 and IGF-I levels were determined by RIA. Methimazole therapy significantly decreased serum T4, IGF-I, epiphyseal growth plate width, and longitudinal growth rate compared to controls. Epiphyseal growth plate width gradually increased when T4 was administered at doses from 2 to 32 μg·kg−1·day−1 (271±14, 311±15 and 324±11 μm), and subsequently decreased when T4 was given at a dose of 64 μg·kg−1·day−1 (267±8 μm). A similar profile was observed for longitudinal growth rate and IGF-I. We conclude that rat tibial growth has a biphasic response to exogenous T4 administration, and that the effects of T4 on tibial growth may be mediated through IGF-I secretion.
Growth hormone increases rate of pubertal maturation
Authors: Darendeliler F. , Hindmarsh P. C. , Preece M. A. , Cox L. , Brook C. G. D.
Published: December 2008

We have performed a retrospective analysis of the pubertal parameters of 134 children with isolated GH insufficiency on GH treatment and compared them to the standards of Tanner and to a recent longitudinal study of growth and development in the United Kingdom. The age at onset of puberty (13.0 years in boys, 12.1 years in girls) was found to be significantly delayed (Mann-Whitney p<0.001), but duration of puberty (1.5 years in both sexes) was shortened (Kolgomarov-Smirnov p<0.01). Skeletal maturity at the onset of puberty was not advanced excluding this as a contributory factor. There was no association between dose of GH administered and the pubertal parameters. The results suggest that GH accelerates the pubertal process.
Neurohypophysial secretion to insulin-induced hypoglycemia and its regulation by endogenous opioids in women
Authors: Johnson Mark R. , Bower Mark , Seck Jonathan R. , Lightman Stafford L.
Published: December 2008

In animals, there is sexual dimorphism of both neurohypophysial peptide secretion in response to stressful stimuli and to the inhibitory effects of opioids. In men, endogenous opioids inhibit the release of oxytocin when AVP secretion is stimulated by insulin-induced hypoglycemia. We have now investigated the role of endogenous opioids in the AVP and oxytocin response to insulin-induced hypoglycemia in women. Twelve subjects, 6 in the follicular and 6 in the luteal phase of the menstrual cycle, were infused on 2 occasions with naloxone (4 mg bolus and 6 mg/h) or saline. Soluble insulin (Human Actrapid®, 0.15 μ/kg, iv) was given and serial blood samples taken. Blood sugar fell significantly (p<0.05) and similarly in all groups. In the follicular phase hypoglycemia led to a rise in plasma AVP from 1.3 ± 0.2 to 1.8 ± 0.2 pmol/l in the saline-infused subjects (NS), and from 1.0 ± 0.1 to 2.0 ± 0.2 pmol/l in the naloxone-infused (p<0.05). AVP rose similarly from 0.6 ± 0.1 to 1.6 ± 0.5 pmol/l (p<0.05) in the luteal phase controls and from 0.8 ± 0.1 to 1.5 ± 0.3 pmol/l (p<0.05) in naloxone-infused subjects in the luteal phase. There were no significant differences between any of these groups. There were no significant changes in plasma oxytocin in any group. We therefore conclude that in women, unlike men, endogenous opioids do not modulate oxytocin or vasopressin release during insulin-induced hypoglycemia.
Effects of D-glucose and β-hydroxybutyric acid on the in vitro development of (pre)chondrocytes from embryos of normal and diabetic rats
Authors: Styrud Johan , Eriksson Ulf J.
Published: December 2008

In order to elucidate cellular mechanisms causing skeletal malformations in offspring of diabetic rats we studied the incorporation of thymidine and sulphate into embryonic (pre)chondrocytes exposed to increased levels of D-glucose and β-hydroxybutyric acid for six days in vitro. The (pre)chondrocytes were prepared from embryos of normal or diabetic rats of a malformation-prone strain or from embryos of normal rats of a non-malformation-prone strain. Diabetic female rats of the former strain are known to produce a high proportion of offspring with mandibular and lumbosacral malformations. Increased β-hydroxybutyric acid caused decreased thymidine incorporation in all types of chondrocytes, and decreased sulphate incorporation in limb bud cells from embryos of normal rats from both strains. Elevated D-glucose levels yielded a slight decrease in thymidine incorporation in mandibular arch cells from embryos of normal rats of the malformation-prone strain, and a marked decrease of both sulphate and thymidine incorporation in mandibular arch cells from embryos of diabetic rats of this strain. The observations suggest that elevated levels of D-glucose or β-hydroxybutyric acid are able to inhibit the differentiation and growth of (pre)chondrocytes and illustrate a selective sensitivity of mandibular arch (pre)chondrocytes to a diabetic environment. The data are compatible with the view that both D-glucose and β-hydroxybutyric acid may cause aberrations in the development of rat mandibular arch chondrocytes, suggesting a role for these compounds in diabetic teratogenesis.