bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition by dexamethasone of arginine vasopressin and ACTH responses to insulin-induced hypoglycemia and cigarette smoking in normal men
Authors: Chiodera P. , Coiro V.
Published: June 2009

Glucocorticoids are known to inhibit the AVP response to osmotic and hemodynamic stimuli in humans. In the present study, we examined whether the AVP response to other primary stimuli, such as insulin-induced hypoglycemia and cigarette smoking was sensitive to inhibition by dexamethasone. The plasma ACTH responses were also measured. Twenty-four normal men were randomly divided into 3 groups of 8 subjects. One group was tested with insulin (0.15 IU/kg in an iv bolus) and another group with cigarette smoking (2 non-filter cigarettes smoked in succession within 10 min) with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin or smoking). The third group was tested with dexamethasone alone (2 or 4 mg in an iv bolus). The administration of dexamethasone (2 or 4 mg) alone did not modify the circulating levels of AVP and ACTH at any time during the next hour. The hypoglycemic response to insulin was similar regardless of dexamethasone treatment. AVP rose sharply in response to both hypoglycemia and smoking, reaching mean peak levels at 45 and 30 min, respectively. After both stimuli, the mean peak levels of AVP were 2.25 times higher than baseline. Pretreatment with dexamethasone (2 or 4 mg) significantly decreased the AVP responses to both hypoglycemia and cigarette smoking. Following pretreatment with dexamethasone (2 or 4 mg) the AVP increments in response to hypoglycemia or cigarette smoking were only 1.7 times higher than baseline. The plasma concentrations of ACTH were strikingly increased by hypoglycemia. The mean peak level was 3.5 times higher than baseline and was reached at 45 min. Pretreatment with dexamethasone (2 or 4 mg) significantly reduced hypoglycemia-induced ACTH increase, with a mean peak response 2.8 times higher than baseline. Cigarette smoking significantly increased the plasma ACTH concentrations. The mean peak level was observed at 20 min and was 1.3 times higher than baseline. The ACTH response to smoking was not significant following pretreatment with dexamethasone (2 or 4 mg). These data show a partial inhibitory effect of dexamethasone on hypoglycemia-and cigarette smoking-stimulated AVP secretion. In addition, the data show suppression by dexamethasone of the ACTH response to cigarette smoking and confirm previous observations of a partial inhibition by glucocorticoids of hypoglycemia-induced ACTH release.
Geographical distribution of subclinical autoimmune thyroid disease in Britain: A study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase
Authors: Prentice Louise M. , Phillips David I. W. , Sarsero Deborah , Beever Karen , McLachlan Sandra M. , Smith Bernard Rees
Published: June 2009

In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake. Consequently, it seems unlikely that environmental factors play a major role in the development of subclinical autoimmune thyroid disease in the geographical areas studied.
Effects of oxytocin upon the endocrine pancreas secretion and glucose turnover in normal man
Authors: Paolisso Giuseppe , Pizza Gennaro , De Riu Stefano , Marrazzo Giuseppe , Sgambato Saverio , Giugliano Dario , Varricchio Michele , D'Onofrio Felice
Published: June 2009

In normal man oxytocin infusion under basal conditions and at pharmacological doses evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin levels. Simultaneous [D-3H]glucose infusion indicated that oxytocin also produced a prompt and significant increase in hepatic glucose output with a secondary increase in glucose disappearance rate. Eight healthy volunteers were studied during euglycemic glucose clamp and simultaneous [D-3H]glucose infusion, during suppression of endogenous pancreatic secretion by cyclic somatostatin (250 μg/h) and during exogenous glucagon (67 ng/min) and insulin (0.15 mU · kg−1 · min−1 from 0 to 120 min and 0.40 mU · kg−1 · min−1 from 121 to 240 min) replacement. During the first 60 min oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels and hepatic glucose output with a simultaneous suppression of the glucose infusion rate. No difference in glucose disappearance and metabolic clearance rates were recorded throughout the clamp irrespective of whether oxytocin was infused or not. So we conclude that oxytocin exerts a hyperglycemic effect through an A-cell stimulation and a glycogenolytic action.
Infusion of β-endorphin has no suppressive effect on the releasing hormone-stimulated pituitary-adrenal-axis of normal human subjects
Authors: Schulte Heinrich M. , Allolio Bruno
Published: June 2009

The existence of a short-loop feedback inhibition of pituitary ACTH release by administration of β-endorphin was postulated. However, data on the effect of peripherally administered β-endorphin in humans are highly controversial. We infused human synthetic β-endorphin at a constant rate of 1 μg · kg−1 · min−1 or normal saline to 7 normal volunteers for 90 min. Thirty min after starting the β-endorphin or placebo infusion, releasing hormones were injected as a bolus iv (oCRH and GHRH 1 μg/kg, GnRH 100 μg, TRH 200 μg) and blood was drawn for measurements of β-endorphin immunoreactivity, all other pituitary hormones, and cortisol. Infusion of β-endorphin resulted in high β-endorphin plasma levels with a rapid decrease after the infusion was stopped. During the control infusion, β-endorphin plasma levels rose in response to CRH. Plasma ACTH and serum cortisol levels in response to the releasing hormone were not different in subjects infused with β-endorphin or placebo. The PRL response to TRH was significantly higher after β-endorphin than after placebo (area under the stimulation curve 1209±183 vs 834±104 μg · 1−1 · h). There was no difference in the response of all other hormones measured. Our data on ACTH and cortisol secretion do not support the concept of a shortloop negative feedback of β-endorphin acting at the site of the pituitary.
Persistent hyperactivity of the parathyroid glands in treated hypothyroid patients
Authors: Furlanetto Reinaldo P. , Castro Marise L. , Kasamatsu Teresa S. , Brandão Cynthia M. A. , Vieira José Gilberto H.
Published: June 2009

Twelve untreated hypothyroid patients were submitted to EDTA infusion and the parathyroid hormone response to the induced hypocalcemia was studied with an amino-terminal specific assay. Eight of these patients were retested 6 months after achieving clinical and laboratory euthyroidism. The PTH response in the pretreatment condition was significantly higher than that obtained in a group of 10 normal individuals; this increased response had not normalized after 6 months of euthyroidism. This persisting hyperresponsiveness can be a contributory factor to the bone hypersensitivity to thyroid hormone replacement seen in hypothyroid patients.
Epidermal growth factor in mice: changes during circadian and female reproductive cycles
Authors: Tuomela Tiina , Viinikka Lasse , Perheentupa Jaakko
Published: June 2009

To clarify the variation of mouse epidermal growth factor production during the 24-h and female reproductive cycles, we measured its concentrations in the plasma, submandibular salivary gland, urine, kidneys and liver of adult male and female mice during consecutive 12-h dark and 12-h light periods, different stages of pregnancy, and lactation. The concentration of epidermal growth factor in the submandibular gland showed no circadian changes. In plasma and in the liver it increased during the dark period, whereas in urine and in the kidneys it peaked in the daytime. In the submandibular gland the concentration decreased during early pregnancy, but it returned to the non-pregnant levels by midpregnancy. In plasma it decreased progressively during pregnancy and recovered during lactation. In urine and the kidneys the concentration of epidermal growth factor increased after early pregnancy; with a further great increase in the kidneys during lactation. In the liver the concentration was clearly below the non-pregnant levels during late pregnancy and lactation.
Effects of a novel gonadotropin-releasing hormone antagonist (ORG 30850) on gonadotropin and prolactin secretion by rat pituitary cells in culture
Authors: Franchimont Paul , Almer Sabine M. , Charlet-Renard Chantal-J. , Daubresse Christine L. , Kicovic Peter P.
Published: June 2009

The effect of a new GnRH antagonist (ORG 30850 ANT) on FSH, LH, and PRL secretion was studied using male rat pituitary cells in monolayer cell culture. In the absence of GnRH, ORG 30850 ANT did not alter spontaneous FSH and LH secretion into culture medium or the cell content of these hormones. In the presence of GnRH (10−8 mol/l), ORG 30850 ANT significantly and dose-dependently inhibited FSH and LH secretion into culture medium while increasing their cell content. Conversely, in the presence of a single dose of ORG 30850 ANT, FSH and LH secretion rose significantly when subjected to increasing amounts of GnRH, whereas the hormonal cell content diminished. Furthermore, inhibition of GnRH-induced FSH and LH release by ORG 30850 ANT was not changed by pre-incubation with the GnRH antagonist regardless of the pre-incubation time. The inhibitory effect of the GnRH antagonist was observed early, with its peak occurring within 6 h of culture. These short-term studies indicate that ORG 30850 ANT specifically inhibits GnRH-induced gonadotropin release into culture medium, exerts no effect on the rate of gonadotropin production in the presence or absence of GnRH, competitively and reversibly inhibits the binding of natural GnRH to its receptors, and does not lead to any modifications in PRL secretion.
Comparison of anterior pituitary hormone levels in the inferior petrosal sinuses and peripheral blood in various pituitary disorders during perihypophysial phlebography
Authors: Lombardi Gaetano , Merola Bartolomeo , Colao Annamaria , Miletto Paolo , De Chiara Giovanni , Spaziante Renato , La Tessa Giuseppe , Renzo Gianfranco Di , Annunziato Lucio
Published: June 2009

The present study aimed at evaluating the anterior pituitary hormone levels in the inferior petrosal sinuses and in the peripheral blood of 55 patients affected by various pituitary disorders and undergoing perihypophysial phlebography on neurosurgical indication or for diagnostic purposes. The results indicated that in 6 patients with Cushing's disease and in 4 with hyperprolactinemia the secreting adenoma could be localized by inferior petrosal sinus sampling. Furthermore, the concentrations of all the pituitary hormones were found to be higher in the right and/or in the left inferior petrosal sinus than in peripheral blood, showing a clear gradient between central and peripheral samples. Moreover, the evaluation of hormone central/peripheral concentration ratios revealed noteworthy differences, namely, that central/peripheral concentration ratios of GH, ACTH, and PRL were significantly higher than those of TSH, FSH, and LH (p<0.01). On the contrary, no significant differences were found when the concentration ratios of GH, ACTH and PRL or TSH, FSH and LH were compared among themselves. This finding may be attributed to at least two factors: the increased pulsatility and the relatively short biological halftime of polypeptic hormones (GH, ACTH, and PRL) compared with glycoprotein hormones (TSH, FSH, and LH).
Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH
Authors: Jensen Lars T. , Jørgensen Jens O.L. , Risteli Juha , Christiansen Jens S. , Lorenzen Ib
Published: June 2009

The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days compared with 2 IU/day (normal replacement dose) (p=0.04). Withdrawal of GH therapy for 14 days resulted in wider variation, but not significantly different from the levels at 2, 4 and 6 IU/day. A dose dependency was found regarding type III procollagen propeptide, showing significantly higher serum concentrations at a GH dose of 4 IU/day compared with 2 IU/day (p=0.001), and of 6 IU/day compared with 4 IU/day (p=0.001). Withdrawal of GH therapy resulted in significantly lower type III procollagen propeptide concentrations compared with those at a GH dose of 4 and 6 IU/day (p=0.03). Serum type III procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective tissue. Serum type I and type III procollagen propeptides may prove useful as monitors of GH therapy, especially regarding the GH dose levels in the individual patients.
Patterns of spontaneous pulsatile secretion of human chorionic gonadotropin and pregnancy specific β1 glycoprotein by superfused placental explants in first and last trimester. Lack of episodic human placental lactogen secretion
Authors: Kaplan M. , Barnea E. R. , Bersinger N. A.
Published: June 2009

We have recently reported that during superfusion of placental explants, human chorionic gonadotropin secretion is episodic. In the present work we have examined, using the superfusion model, the pattern of secretion of other glycoprotein hormones, pregnancy specific β1 glycoprotein and human placental lactogen, in the first trimester and term placenta. This was done by evaluating the pulsatile pattern by two different computerized programmes. By using different sampling intervals (6-0.5 min) of the effluent, two distinct patterns of hCG secretion were detected in the first trimester: a short one, occurring every 8-9 min and the other every 18-25 min. In contrast, at term the only episodic pattern detected was every 40-50 min, with a low amplitude, 20-30% above baseline, and a declining baseline. In two out of seven placentas, no pulsatility was detected. The secretion of pregnancy specific β1 glycoprotein was pulsatile, occuring every 14-15 min in the first trimester and every 6-7 min at term. Finally, the secretion of human placental lactogen at term was not pulsatile. The levels of this glycoprotein in the first trimester placenta were below detection limits. In conclusion, the patterns of the three glycopoproteins during superfusion are different, suggesting different paracrine/autocrine control mechanisms. The dynamic superfusion model also enables identification of thus far not reported gestational age-dependent differences in the secretion pattern of hCG and pregnancy specific β1 glycoprotein.
Subtle primary hypothyroidism in patients treated for acute lymphoblastic leukemia
Authors: Pasqualini Titania , McCalla June , Berg Stacy , Poplack David G , Rose Susan R , Nisula Bruce C , Cassorla Fernando
Published: June 2009

We evaluated serum thyroid hormone and thyroid antibody levels, the serum TSH response to TRH, and the circadian pattern of serum TSH in 10 children and adolescents after radiation therapy for acute lymphoblastic leukemia. Four patients had received central nervous system preventive cranial irradiation and intrathecal chemotherapy, and the remaining 6 patients were treated with craniospinal irradiation for central nervous system relapse. Serum total T4 and T3 concentrations were within the normal range and thyroid antibodies were negative in all patients. Four patients who had received craniospinal irradiation had low free T4 levels. Prior to TRH administration, the overall mean serum TSH concentration was 5.4±1.3 mU/l, and the mean peak response to TRH was 33±6.5 mU/l. Both were significantly increased when compared to the levels observed in our control population (p<0.05 and <0.025, respectively). The overall mean nadir diurnal TSH was 3.6±0.8 mU/l, and the mean peak nocturnal TSH was 6.9±1.3 mU/l, both significantly elevated when compared to normal children (p<0.025). The mean nocturnal TSH surge, however, was not significantly different from normal. Four of 6 children treated with craniospinal irradiation, and one of four children treated with cranial irradiation had increased basal and peak serum TSH concentrations in response to TRH. One of the patients treated with cranial irradiation had an abnormal nocturnal TSH surge. We conclude that subtle primary hypothyroidism is relatively common in patients with acute lymphoblastic leukemia, particularly in those who have been treated with craniospinal irradiation.
Relations between diurnal variations in serum osteocalcin, cortisol, parathyroid hormone, and ionized calcium in normal individuals
Authors: Nielsen Henning Kaspersen , Laurberg Peter , Brixen Kim , Mosekilde Leif
Published: June 2009

Serum osteocalcin varies in a diurnal rhythm, with peak values during the night and minimum levels before noon, but the factors controlling this rhythm are unknown. In this study, we evaluated the temporal relations between the osteocalcin rhythm and variations in serum concentrations of cortisol, intact parathyroid hormone (PTH(1-84)), and ionized calcium (Ca2+) in 15 normal volunteers, aged 22-46 years. Serum cortisol varied in a typical way preceding inverse changes in serum osteocalcin by about 4 h (r=0.78, p<0.0001). Changes in serum osteocalcin following the early morning increase in serum cortisol were statistically indistinguishable from the changes seen after oral administration of 2.5 or 10 mg of prednisone. Serum PTH (1-84) showed a diurnal rhythm (p<0.01) with peak values (4.06±0.42 pmol/l) at 20.30 h and nadir (2.81±0.10 pmol/l) around 10.30 h, preceding changes in serum osteocalcin in the same direction by 5 h (r=0.55, p<0.02). Prednisone at a dose of 10 mg did not change the time course significantly. Serum Ca2+ varied in an almost bi-phasic pattern (p<0.01) with maximal mean levels around 16.30 and 09.30 h and minimal levels around 05.30 and 14.30 h. Serum Ca2+ correlated inversely with PTH (1-84) (r=0.53, p<0.01), and serum osteocalcin was inversely related to Ca2+ at concurrent time points (r=0.59, p<0.005). Prednisone caused a 2-3 h lasting increase in serum Ca2+ 3-5 h after ingestion (p<0.001). In conclusion, our results suggest that cortisol is strongly associated to the diurnal rhythm in serum osteocalcin. The biological relevance of the reported relation between serum osteocalcin and PTH (1-84) and serum Ca2+ is uncertain.
Why no simple relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function in autoimmune thyroid disease?
Authors: Okamoto Yasuyuki , Hamada Noboru , Fujisawa Toshimichi , Noh Jaeduk , Yamakawa Junichi , Ohno Mariko , Ito Kunihiko , Morii Hirotoshi
Published: June 2009

We have reported that some anti-thyroid peroxidase antibodies inhibit the activity of thyroid peroxidase in vitro. These thyroid peroxidase activity-inhibiting immunoglobulins seem to inhibit thyroid function in some patients, but the relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function is not simple. We designed this study to explore this lack of a simple relationship. We stained immunoglobulin G deposits by immunofluorescence staining or the peroxidase-antiperoxidase method, and stained endogenous thyroid peroxidase activity by enzyme histochemistry in thyroid sections. When cryostat thyroid sections were incubated with thyroid peroxidase activity-inhibiting immunoglobulins, immunoglobulin G deposits were seen as lines of stain on the apical border and as intracellular staining, and endogenous thyroid peroxidase activity was inhibited. In paraffin-embedded thyroid sections from 5 Hashimoto's patients and 6 Graves' patients, immunoglobulin G deposits were not found on the apical border of the follicular epithelium. In frozen thyroid sections from 22 Graves' patients, no clear deposits of immunoglobulin G on this apical border were seen. In organ-cultured thyroid slices incubated with thyroid peroxidase activity-inhibiting immunoglobulins, endogenous thyroid peroxidase activity was not inhibited. In conclusion, thyroid peroxidase activity-inhibiting immunoglobulins may reach its antigen only with difficulty. This is one of the reasons why no simple relationship is observed between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function.
Inhibitory effects of ionophore A23187 on the release of thyroid hormone and colloid reabsorption in mouse thyroid glands
Authors: Mori-Tanaka Misuzu , Tajima Koji , Miyagawa Jun-ichiro , Oda Yasuo , Matsui Ikuko , Kitajima Koichi , Hanafusa Toshiaki , Tarui Seiichiro , Mashita Kazuhiko
Published: June 2009

The effect of the ionophore A23187 on a. the release of thyroid hormone from perifused mouse thyroid glands and b. the morphological changes in follicular epithelial cells was evaluated. A23187 at a concentration of 5 μmol/l significantly inhibited both the TSH- and the forskolin-stimulated release of T3 and T4. In the presence of 3-isobutyl-1-methylxanthine or (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) RO 20-1724, A23187 did not affect the forskolin-stimulated release of cAMP, but did inhibit the release of T3 and T4 stimulated by forskolin. Light and electron microscopic evaluation of the follicular epithelial cells of mouse thyroid tissues following 1-h stimulation with forskolin showed numerous pseudopods engulfing luminal colloid of various size and the presence of reabsorbed colloid droplets in the apical cytoplasm. Quantitative electron microscopic analysis revealed that the addition of the ionophore A23187 reduced the number of reabsorbed colloid droplets to one eighth in follicular epithelial cells. These observations suggest that the increase in intracellular Ca2+ induced by the ionophore A23187 inhibits the TSH-stimulated thyroid hormone release independently of the cAMP level, and that the suppression of thyroid hormone release may be due to an inhibition of colloid reabsorption.
Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy
Authors: Bech Karine , Høier-Madsen Mimi , Feldt-Rasmussen Ulla , Jensen Bente Møller , Mølsted-Pedersen Lars , Kühl Claus
Published: June 2009

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p<0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p<0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p<0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.
The effect of acute hyperglycemia on the plasma C-peptide response to intravenous glucagon or to a mixed meal in insulin-dependent diabetes mellitus
Authors: Gjessing H. J. , Reinholdt B. , Faber O. K. , Pedersen O.
Published: June 2009

The dose-response relationships between prestimulatory blood glucose concentration and the plasma C-peptide responses to stimulation with 1 mg of glucagon iv or a standard mixed meal were studied in 8 C-peptide positive patients with insulin-dependent diabetes mellitus. Hyperglycemia was maintained for 90 min before stimulation using a hyperglycemic clamp technique. Each test was performed at the steady state blood glucose levels ~5, ~12, and ~20 mmol/l. The glucose potentiation of the incremental plasma C-peptide area under the curve at the two levels of hyperglycemia in percent of the area at normoglycemia (median and range) was 343% (53-1053) (p<0.05) and 341% (267-1027) (p<0.05) after glucagon and 140% (76-227) (NS) and 251% (95-1700) (p<0.05) after the meal. The corresponding relative glucose potentiation of plasma C-peptide 6 min after stimulation with glucagon was 124% (100-427) (p<0.02) and 144% (100-209) (p<0.05). There was no significant difference in the degree of glucose potentiation at ~12 or ~20 mmol/l. Furthermore, there was no significant difference in the degree of glucose potentiation of the different estimated values of B-cell function. In conclusion, the plasma C-peptide responses to iv glucagon or to a standard test meal were markedly potentiated by acute hyperglycemia in insulin-dependent diabetes mellitus. No further potentiation was, however, obtained when the prestimulatory blood glucose concentration was raised above 12 mmol/l. These findings contrast those reported in non-insulin-dependent diabetes, where endogenous insulin secretion is potentiated further when the blood glucose concentration is raised to ~20 mmol/l.
Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone
Authors: Scheven Ben A. A. , Hamilton Nicola J.
Published: June 2009

Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.
Inhibition of growth hormone secretion by activin A in human growth hormone-secreting tumour cells
Authors: Kitaoka Masafumi , Takano Kohji , Tanaka Yuji , Kojima Itaru , Teramoto Akira , Ogata Etsuro
Published: June 2009

Effect of activin A on growth hormone secretion was studied in primary culture of 8 human GH-secreting adenomas, which were responsive to TRH in vivo. When studied in vitro, basal GH secretion was reduced in all cases when cells were pre-incubated for 48 h with activin A at a concentration of 5×10−9 mol/l or greater. Pretreatment of GH-secreting cells with 1× 10−9 mol/l activin A did not affect either basal secretion or cellular content of GH. These tumour cells also responded to TRH in vitro and the GH response to TRH was completely blocked in cells pretreated with activin A. Activin A slightly reduced the increase in cytoplasmic free calcium concentration induced by TRH. Furthermore, pretreatment of the cells with activin A attenuated GH secretion induced by A23187 or 12-O-tetradecanoyl phorbol-4-acetate, agents which bypass receptor-mediated generation of second messengers. These results indicate that activin A inhibits GH secretion by directly acting on human GH-secreting cells and that activin A inhibits the action of TRH by acting on multiple steps in the messenger system.
The effect of human growth hormone therapy on GH binding protein in GH-deficient children
Authors: Hochberg Zeev , Barkey Ronnie J. , Even Lea , Peleg Israela , Youdim Moussa B. H. , Amit Tamar
Published: June 2009

Previous studies have described the close similarity of the GH binding protein to the liver membrane GH receptor. Since GH regulates its own liver receptors, we examined the effects of short- and long-term hGH therapy on GH binding protein in children with GH deficiency. Six GH-deficient children received their first hGH dose ever, and the pharmacodynamics of serum GH was followed for 12 h, along with measurements of GH binding protein activity. Over the first 6 h, serum GH and GH binding protein activity exhibited a parallel increase, followed by gradual decrease. At 8 h, some of the patients exhibited an apparent second peak in GH binding protein, despite the continuous decrease in serum hGH. During the period of hGH treatment, serum GH binding protein increased progressively over a period of 6 months. In a second uncontrolled group of 7 GH-deficient patients who had been treated with hGH for 30-36 months, GH binding protein activity was also significantly higher than pretreatment values. We suggest that the short-term pharmacodynamic changes probably represent the endogenous turnover of the GH receptor, whereas the elevated GH binding protein activity on hGH treatment may reflect up-regulation of the GH receptor.
Increased urinary free cortisol and decreased serum corticosteroid-binding globulin in polycystic ovary syndrome
Authors: Invitti Cecilia , Giraldi Francesca Pecori , Dubini Antonella , De Martin Martina , Cavagnini Francesco
Published: June 2009

The adrenal participation in the pathogenesis of polycystic ovary syndrome is still under debate. In order to reappraise androgen and glucocorticoid secretion in this disease, we measured serum androstenedione, dehydroepiandrosterone-sulphate, total and free testosterone, sex hormone-binding globulin, LH, FSH, PRL, cortisol, corticosteroid-binding globulin, and urinary free cortisol in 45 women with polycystic ovary syndrome and 27 controls, subdivided in obese and normal-weight subjects. Androstenedione, total and free testosterone were significantly increased, whereas sex hormone-binding globulin tended to be reduced in patients with polycystic ovary syndrome compared with controls, reaching a significant difference between obese patients and matched controls. Free testosterone and sex hormone-binding globulin were significantly increased and reduced, respectively, in obese compared with normal-weight patients. Urinary free cortisol and serum corticosteroid-binding globulin were significantly increased (p<0.001) and decreased (p<0.005), respectively. Urinary free cortisol exceeded the upper limit of the normal range in 50% of our patients. No appreciable differences were found in PRL and cortisol levels. Besides confirming a hyperandrogenic state, our findings point to an overactivity of the hypothalamic-pituitary-adrenal axis with subsequent diminution of corticosteroid-binding globulin in polycystic ovary syndrome. They also indicate that urinary free cortisol is not a reliable index in differentiating polycystic ovary syndrome from Cushing's disease.
Biosynthetic growth hormone changes the collagen and elastin contents and biomechanical properties of the rat aorta
Authors: Brüel Annemarie , Oxlund Hans
Published: June 2009

The biomechanical and biochemical properties of aortas from female rats treated with biosynthetic human GH (b-hGH) for 80 days were investigated. b-hGH was administered at a dose of 5 mg·kg−1·d−1. Treatment with b-hGH increased the body weight by 75% and the diameter of the aorta by 14% compared with the control group. The concentration of collagen and the relative amount of collagen type I were increased, and the concentration of elastin was decreased. Aortas from the b-hGH-treated group showed increased extensibility in the regions corresponding to physiological load values (i.e. 100-200 mmHg), and increased stiffness in regions with higher load values. The increased extensibility at low load values corresponds well with the loss of elastin, and the increased stiffness at higher load values with the increase of collagen and relative increase of collagen type I. These alterations induced by the growth hormone treatment might influence the elasticity and recoiling properties of the aorta.
Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy
Authors: Maruo Takeshi , Matsuo Hiroya , Mochizuki Matsuto
Published: June 2009

Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured with or without graded doses of T3 or T4 for 5 days in a serum-free condition. Addition of T3 (10−8 mol/l) resulted in the maximum increase in daily secretion of progesterone, estradiol-17β as well as hCGα, hCGβ, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17β secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 (10−8 mol/l) enhances 3β-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 (10−8 mol/l) on the trophoblast endocrine function were also found with the use of T4 (10−7 mol/l). Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function.
Effects of decreasing exogenous GnRH pulse frequency on FSH and inhibin secretion in men with idiopathic hypogonadotropic hypogonadism
Authors: Wu Frederick CW , Wallace Euan M , Howe David C , Kacser Elaine M , Sellar Robin E
Published: June 2009

The potential importance of GnRH pulse frequency modulation and steroid or inhibin negative feedback in the selective control of pituitary FSH secretion was investigated in 5 adult men with idiopathic hypogonadotropic hypogonadism in whom plasma testosterone has been previously normalized by pulsatile GnRH therapy. The effects of decreasing frequency of pulsatile iv GnRH administration from 2- to 4-hourly for 7 days were examined at constant GnRH bolus dose or constant daily dose and also with interrupted gonadal steroid feedback using a combination of an anti-androgen (flutamide 250 mg t.i.d.) and an aromatase inhibitor (aminogluthetimide 125 mg b.d.) orally for a further 7 days. Slowing GnRH pulse frequency from 2- to 4-hourly did not alter mean plasma FSH at constant bolus dose or constant total daily doses of GnRH. In two subjects with subnormal but not in another two with normal testicular volumes, FSH rise was observed when the 4-hourly GnRH pulse frequency was combined with the interruption of steroid feedback. These results are not compatible with a major role for GnRH pulse frequency modulation in the regulation of pituitary FSH secretion in the presence of normal gonadal steroid feedback. Irrespective of FSH concentrations, plasma inhibin immunoactivity did not change significantly with the alteration in GnRH pulse frequency. The role of inhibin in the control of FSH therefore remains undefined in men.
Impaired conversion of cortisol to cortisone in chronic renal insufficiency - a cause of hypertension or an epiphenomenon?
Authors: Vierhapper H. , Derfler K. , Nowotny P. , Hollenstein U. , Waldhäusl W.
Published: June 2009

To study the possible impairment of 11 β-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N=15) and without (N=7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p<0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22±12%) and in healthy subjects (20±5%). However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7±0.4 (hypertensive patients 0.5±0.2; normotensive patients 1.1±0.4; controls 1.9±0.9, p<0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p<0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients.
Differential effects of insulin-like growth factors I and II on growth, differentiation and glucoregulation in differentiating chondrocyte cells in culture
Authors: Bhaumick Banani , Bala R. Marvin
Published: June 2009

Insulin-like growth factors I and II have been shown differentially to affect the growth and carbohydrate metabolism of differentiating cartilage developed from mouse embryonic limb buds in organ culture. To gain insight into the relative importance of IGF-I and II actions in different stages of development of cartilage we have established a primary culture of differentiating chondrocytes from mouse embryonic limb buds. Trypsin digested limb bud cells from 9-11 day old mouse embryos differentiated into chondrocytes by 5-7 days in culture. At all stages of differentiation, distinct receptors of IGF-I and II were observed. IGF-I stimulated growth and sulphate incorporation of the non-differentiated and differentiated chondrocytes. IGF-II stimulated growth of the non-differentiated cells and had no effect on growth or sulphate incorporation by the differentiated cells. IGF-II, however, stimulated the glucose uptake by the cells at all stages of differentiation. These data confirm our previous suggestion that IGF-I in cartilage is the regulator of growth and differentiation, while IGF-II may be an important regulator of glucose metabolism in the tissue.
Increased soluble interleukin 2 receptor levels in autoimmune thyroid disease
Authors: Nakanishi Kimio , Taniguchi Yoshiyasu , Ohta Yasuyuki
Published: June 2009

We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497±649 (mean ± sd), 641±137 vs 221±63 103 U/l, p<0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r=0.684, p<0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411±148 vs 221±63 103U/l, p<0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.
Influence of pregnancy on the serum prolactin level following prolactinoma surgery
Authors: Hirohata Taizo , Uozumi Tohru , Mukada Kazutoshi , Arita Kazunori , Kurisu Kaoru , Yano Takashi , Takechi Akihiko , Onda Jun
Published: June 2009

We studied the influence of pregnancy on the serum prolactin levels after surgery in 35 patients with prolactinomas. Eighteen out of 22 patients with postoperative normalization of the prolactin level were able to achieve repeated spontaneous pregnancies and endocrine cure by surgery alone, but the other 4 had recurrent hyperprolactinemia. Thirteen patients with persistent hyperprolactinemia after surgery achieved one pregnancy with or without bromocriptine treatment, but did not achieve a second one owing to an increase in the prolactin level after delivery. None of the patients with postoperative hyperprolactinemia showed spontaneous normalization of the prolactin level or restoration of menstruation after delivery. In these 13 patients, the mean increase from the postoperative to the post-delivery prolactin level was less for the patients with bromocriptine-induced pregnancy than for those with spontaneous pregnancy. It is concluded that pregnancy did not adversely affect the serum prolactin level in the patients with a normal post-operative level.
Inhibition of protein kinase C by staurosporine increases estrogen secretion by rat Sertoli cells
Authors: Lambert Ann , Talbot J. Alan , Mitchell Robert , Robertson William R.
Published: June 2009

We have examined the effect of inhibition of protein kinase C activity by staurosporine on estradiol secretion by Sertoli cells isolated from 8–10 days old rats. Staurosporine lead to a dose-related increase in estradiol secretion independent of FSH, such that with 100 nmol/l staurosporine basal estradiol levels increased 10-fold. The maximal response seen with staurosporine alone (100 nmol/l) or in combination with FSH (0.4–8 IU/l) was similar to that seen with a saturating dose of FSH (8 IU/l). There was no evidence of synergy between FSH and staurosporine. Activation of protein kinase C by phorbol 12,13 dibutyrate (10−7 mol/l) resulted in a 53–74% inhibition of estradiol production provoked by FSH (8 IU/l), staurosporine (5–100 nmol/l) or staurosporine in combination with FSH. Staurosporine (5–100 nmol/l), in the absence or presence of FSH, was unable to overcome inhibition of estradiol secretion by phorbol ester, indicating the presence of at least two independent binding sites on protein kinase C for these molecules. Forskolin (1 μmol/l)- and dibutyryl cAMP (1 mmol/l)-stimulated estradiol secretion was inhibited by 31±5% and 64±5% respectively, by phorbol 12,13 dibutyrate (10−7 mol/l). We conclude that FSH-induced estradiol secretion in immature rat Sertoli cells is affected by protein kinase C activity.
Circulating thyroglobulin measurements by homologous radioimmunoassay in dogs with thyroid carcinoma
Authors: Verschueren C. P. , Selman P. J. , Mol J. A. , Vos J. H. , van Dijk J. E. , Sjollema B. E. , de Vijlder J. J. M.
Published: June 2009

Circulating thyroglobulin was measured in 20 dogs with thyroid cancer, using a homologous polyclonal radioimmunoassay. Plasma Tg levels exceeded the normal range in 14 (70%) dogs, and ranged from 6 to 2902 μg/l (median 608). Plasma Tg levels tended to decrease from follicular carcinomas to solid-follicular carcinomas, to solid carcinomas (p<0.05). Plasma Tg levels were also higher in scintigraphically hot tumours than in cold ones. Other relationships between circulating Tg and clinical, pathological, and functional parameters were not found, except a poor (R=0.49) but significant (p=0.04) correlation between Tg and T4 levels. Plasma Tg was measured before surgery and at least once during followup, in 9 dogs. After hemithyroidectomy, a decrease was observed in 8 dogs. In 7 of these 8 dogs, plasma Tg levels declined within the reference range at the first postoperative sample. In the ninth dog, where metastases were detected 14 months after surgical treatment, plasma Tg slightly increased, yet within normal range. It is concluded that measurement of plasma Tg levels might be useful for monitoring the postoperative course of the disease in individual dogs with thyroid cancer.