bluuebunny/crossref_metadata_2025 huggingface dataset:
Thelarche variant: A new syndrome of precocious sexual maturation?
Authors: Stanhope Richard , Brook Charles C. D.
Published: June 2009

We describe 10 girls (mean age 3.7 years, range 1.9-6.9) with precocious sexual maturation and clinical findings intermediate between those of premature thelarche and central precocious puberty. Studies of spontaneous gonadotropin secretion and ovarian ultrasound morphology also revealed findings intermediate between those of isolated premature thelarche and central precocious puberty. There was no response in 6 of the girls treated with GnRH analogue, whether administered intranasally, sc, or by monthly depot injections. We have called this condition thelarche variant because the gonadotropin independence and cyclical nature of breast development may well be due to a lesion of folliculogenesis.
Immunoreactive insulin-like growth factor II in urine
Authors: Zumkeller Walter , Hall Kerstin
Published: June 2009

Insulin-like growth factor II and insulin-like growth factor binding protein-1 were identified and quantified in the urine of 23 healthy subjects between 17 and 76 years of age. IGF-II was measured after separation by gel chromatography at low pH and compared with IGF-I levels in the same samples, whereas IGF binding protein-1 was measured in dialysed urine. Urinary IGF-II was found at much higher concentrations than IGF-I (mean ±sem: 717±69 vs 110±5 ng/mmol creatinine). The chromatographic profile indicates that pro-IGF-II may also be present. The concentrations of IGF-II appear to be less variable than the other reported parameters. The mean IGF binding protein-1 concentrations in these urine samples was 414±83 ng/mmol creatinine. IGFs in the urine are in part bound to binding proteins.
Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis
Authors: Noh Jaeduk , Hamada Noboru , Saito Hifumi , Yoshimoto Midori , Iwasaki Hiroyuki , Ozaki Osamu , Okamoto Yasuyuki , Ito Kunihiko , Morii Hirotoshi
Published: June 2009

Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.
The blunting of the thyrotropin response to repeated thyrotropin-releasing hormone administration is reduced by dopaminergic blockade both at normal and elevated serum levels of thyroid hormones
Authors: Erfurth Eva Marie T. , Attewell Robyn , Hedner L. Pavo
Published: June 2009

Fifteen premenopausal women were investigated in the follicular phase of the menstrual cycle with two TRH tests within an interval of 48 to 96 h. Ninety min before each TRH test either 10 mg metoclopramide or saline was injected iv in randomized order. The same procedure was repeated in the following menstrual cycle after pretreatment with T4 (0.5 mg daily for 6-14 days). At least 2 months later the same procedure was repeated with T3 pretreatment (60-120 μg for 6-8 days) in 9 of them. A multiple regression analysis was used in modelling the relationships between TSH release and serum free T3, T4 and estradiol levels, adjusting for the presence of metoclopramide and the order of the test. No correlation was found between the TSH response to TRH and the serum estradiol level. The TSH response to the second TRH test was approximately half the first one, both in the control situation and after treatment with T4 or T3. The blunting of the TSH response to the second TRH administration was significantly reduced by metoclopramide, both at normal and elevated thyroid hormone levels, suggesting that a dopaminergic mechanism takes part in the blunting.
The effect of pre-operative potassium iodide therapy on antibody production
Authors: Wilson R. , Mc Killop J. H. , Thomson J. A.
Published: June 2009

Previous studies have suggested that iodide may increase the incidence of thyroid disease and antithyroid antibodies in predisposed individuals. This study has considered the effects of pre-operative potassium iodide (60 mg twice daily, for 10 days) on the immune system of patients with Graves' disease. The treatment regimen used maintained all patients in a clinically and biochemically euthyroid state prior to surgery. Potassium iodide significantly increased serum thyrotropin receptor antibody levels and B cell activity as determined by increased immunoglobulin production from mitogen stimulated peripheral blood lymphocytes. These effects were not observed in the two control groups of Graves' disease patients. Our in vivo findings would support previous in vitro work showing that potassium iodide does act on the immune system and this may be the mechanism by which iodide induces thyroid dysfunction in predisposed individuals.
Improved sensitivity of serum thyrotropin measurements. Studies on serum sex hormone-binding globulin in patients with reduced serum thyrotropin
Authors: Faber Jens , Gam Arne , Siersbæk-Nielsen Kaj
Published: June 2009

Most serum TSH assays have a working sensitivity (i.e. the lowest TSH value with an inter-assay co-efficient of variation below 10%) around 0.15-0.4 mU/l, which also is the critical area for cut off for further thyroid profile testing when serum TSH is used as a "first line test". A new assay (BeriLux hTSH) based on chemiluminescence was evaluated, and demonstrated a theoretical sensitivity (mean + 2 sd of the zero standard) of 0.005 mU/l and a working sensitivity as low as 0.04 mU/l. Reference range was 0.18-2.60 mU/l (N=33). Sixty-eight percent (13/19) of hyperthyroid patients had serum TSH <0.005 mU/l, all had serum TSH <0.037 mU/l. We studied two groups of patients with normal free T4 and T3 indices but serum TSH <0.15 mU/l as measured by an immunoradiometric assay. Thirty-five percent (7/20) of patients with nontoxic goitre and 5% (1/20) of L-T4 treated patients had serum TSH <0.005 mU/l; and in 60% (11/20) and 30% (6/20), respectively, the levels overlapped the total range for hyperthyroidism. Serum levels of sex hormone-binding globulin expressed as percent of the reference median for the relevant sex (SHBG%) were elevated in both groups of patients (p<0.01). Approximately 50% of those with serum TSH overlapping the hyperthyroid range had serum SHBG% levels above reference range. In conclusion, this assay seems superior to most previously reported assays concerning working sensitivity, but it still leaves us with a group of clinically euthyroid patients who has unmeasurably low serum TSH. Many of these patients have increased serum SHBG%, and might in fact be subclinically hyperthyroid.
Characterization of melatonin receptors in the ram pars tuberalis: influence of light
Authors: Pelletier Jean , Castro Bertrand , Roblot Georges , Wylde Renée , de Reviers Marie-Madeleine
Published: June 2009

The present study was conducted to assess the binding of [125I]melatonin to frozen unfixed sections of pars tuberalis/median eminence tissue from Ile-de-France rams exposed or not exposed to light before slaughter. The specificity of [125I]melatonin binding to the pars tuberalis tissue was revealed by autoradiography and the magnitude of binding as related to the pars tuberalis area was determined after incubation and counting of pars tuberalis/median eminence sections. Subsequent studies with sections incubated with [125I]melatonin indicated that 1. the binding sites were saturable; 2. binding was stable for 24 h at 20°C, but unstable at 28 or 37°C; 3. melatonin and [12 7I]melatonin had a similar potency to compete with [125I]melatonin for binding sites, whereas other ligands such as serotonin or N-acetylserotonin were devoid of activity, and 4. by Scatchard analysis, the constant affinity Ka was found to be high in the 1010 l/mol range. Rams exposed to light throughout the night prior to slaughter presented a significant increase in the apparent number of [125I]melatonin binding sites in comparison to animals maintained under darkness (2.25±0.30 vs 1.01±0.17 fmol/mm2 pars tuberalis, p<0.01), whereas Ka values were similar in both groups. These results indicate the presence of true melatonin receptors in the pars tuberalis of the ram. Furthermore, they suggest that their apparent number is light-dependent.
Characterization of the acidic forms of ovine pituitary luteinizing hormone
Authors: Keel B. A. , Harms R. L. , Grotjan H. E.
Published: June 2009

The naturally occurring acidic forms of ovine pituitary LH were examined by chromatofocusing. Immunoreactive oLH eluted as six variants (elutions pHs of >7.4, 6.83, 6.59, 6.23, 5.5-4.0, and <4.0, designated as "basic forms" and variants II-VI, respectively). In rams, the percentage in each variant averaged 46, 9, 28, 10, 5 and 2, respectively, of the total LH recovered. oLH from non-implanted wethers or wethers implanted with dihydrotestosterone, E2 or dihydrotestosterone +E2 eluted as six similar variants but differences were noted in the distribution of oLH among the variants. Compared to rams, pituitary extracts from non-implanted and dihydrotestosterone-implanted wethers contained significantly higher percentages of oLH eluting as basic forms. In contrast, E2- or dihydrotestosterone-implanted wethers exhibited significantly higher percentages of oLH in the acidic variants. Each of these variants was demonstrated to contain biologically active oLH using an in vitro bioassay. Furthermore, the basic forms of oLH were the most abundant biologically active forms present in pituitary extracts. These results suggest that in addition to the seven basic forms of oLH previously described, there are at least five naturally occurring acidic forms of oLH in pituitary extracts which are biologically active, and the distribution of pituitary oLH among its isohormones, including the acidic forms, appears to be modified by steroids.
Effect of 2-buten-4-olide, an endogenous suppressant of feeding, on reproductive function in rats
Authors: Shitsukawa Keiji , Irahara Minoru , Kanematsu Toyokazu , Azuma Keijiro , Aono Toshihiro
Published: June 2009

The effects of 2-buten-4-olide, an endogenous feeding suppressant, on the estrous cycle and LH secretion were studied to determine the influence of this compound on reproductive function. Estrous cycling female Wistar rats were treated ip with 2-buten-4-olide (0, 30 or 100 mg·kg−1·day−1) for 2 weeks. Treatment with 100 mg·kg−1·day−1delayed the estrous cycle. 2-Buten-4-olide increased the pituitary content of LH (1651.3±164.4 vs 927.7±65.1 ng/pituitary; p<0.01), and decreased the serum LH level compared with the control level in diestrus (0.16±0.01 vs 0.26±0.03 μg/l; p<0.05). However, it did not affect the GnRH content of the mediobasal hypothalamus. The direct effects of 2-buten-4-olide on the pituitary response to GnRH was examined by perifusing the pituitary. Medium containing 2-buten-4-olide (10−4 mol/l) suppressed the pituitary response to GnRH (2 μg/l) (percent increase at 50 min after start of GnRH stimulation: 180±47 vs 406±66%; p<0.05). These findings suggest that 2-buten-4-olide is involved in the regulation of pituitary gonadotropin secretion directly by suppressing the pituitary responsiveness to GnRH, and that 2-buten-4-olide may play an important role in starvation-induced anestrus.
Iodine deficiency diseases in Switzerland one hundred years after Theodor Kocher's survey: A historical review with some new goitre prevalence data
Authors: Bürgi Hans , Supersaxo Zeno , Selz Beat
Published: June 2009

In certain regions of Switzerland, before prophylaxis, 0.5% of the inhabitants were cretins, almost 100% of schoolchildren had large goitres and up to 30% of young men were unfit for military service owing to a large goitre. Iodization of salt was introduced in 1922 at 3.75 mg I per kg and the iodine content was doubled twice, in 1962 and 1980, to the present 15 mg I per kg. In 1988, 92% of retail salt and 76% of all salt for human consumption (including food industry) was iodized, even though its use is voluntary. Urinary iodine excretion, previously between 18 and 64 μg per per day, has now risen to 150 μg per day. No new endemic cretins born after 1930 have been identified. Goitre disappeared rapidly in newborns and schoolchildren, more slowly in army recruits, and incompletely in elderly adults. In some Cantons (by constitution in charge of health matters and the salt monopoly) which allowed iodized salt only in 1952, disappearance of goitre lagged behind accordingly, proof that iodized salt was the cause of regression. The Swiss data provide evidence that isolated deafness, mental deficiency, and short stature, each without the other attributes of cretinism have also decreased. Adverse effects of iodized salt were minimal, possibly because the initial iodine content of salt was chosen very low. Iodization of salt has proved a highly cost-effective preventive measure in Switzerland.
Effects of galanin and calcitonin gene-related peptide on insulin and glucagon secretion in man
Authors: Ahrén Bo
Published: June 2009

To study the influence of the pancreatic neuropeptides, galanin and calcitonin gene-related peptide, on insulin and glucagon secretion in man, synthetic porcine galanin (80 pmol·kg−1·min−1; N=6) or synthetic human calcitonin gen-related peptide (10 pmol·kg−1·min−1; N = 5) was infused intravenously in human volunteers. Following 5 min of infusion, arginine (5 g bolus + 10 mg·kg−1·min−1) was given. Galanin did not affect basal or arginine-stimulated insulin secretion judged from determinations of plasma insulin and C-peptide. Similarly, galanin did not affect arginine-stimulated glucagon secretion. Calcitonin gene-related peptide did not affect basal or arginine-stimulated insulin or glucagon secretion. However, calcitonin gene-related peptide slightly potentiated the arginine-induced hyperglycemia (p<0.01). Thus, in man, galanin has no influence on insulin or glucagon secretion when infused at 80 pmol·kg−1·min−1, whereas CGRP at 10 pmol·kg−1·min−1 induces slight hyperglycemia.
Ovarian response patterns to human menopausal gonadotropin in mixed hyperandrogenemia
Authors: Hamori Miklos , Török Attila , Zwirner Manfred , Tinneberg Hans-Rudolf
Published: June 2009

Twenty-eight hyperandrogenemic women suffering from infertility owing to chronic anovulation were treated with hMG. Only 7 patients exhibited the typical polycystic ovarian appearance of multiple subcortical cysts, however, a wide range (6-15 cm3) of ovarian volume was observed. The LH/FSH ratio was consistently lower than 2.5 and circulating androgens of both ovarian and adrenal origin were elevated. The 4 days dexamethasone suppression test showed more than 80% suppression of dehydroepiandrosterone-sulphate and a variable (40-60%) reduction of testosterone and androstenedione levels. Two different patterns of follicular development were observed in response to hMG. Sixteen patients exhibited polycystic ovarian reaction, whereas 12 women had a follicular growth pattern similar to that seen in hMG-stimulated normo-ovulatory subjects. Patients with polycystic ovarian reaction showed a significantly increased androstenedione response to hMG when compared with the other group. Moreover, the non-stimulated ovarian volume was found to be markedly greater than in subjects without polycystic reaction. Thus, ovarian stimulation of patients with mixed hyperandrogenemia may elucidate the presence of borderline polycystic ovaries; furthermore the increased accumulation of androstenedione may suggest an inherent ovarian failure.
On the usefulness of levothyroxine suppressive therapy in the medical treatment of benign solitary, solid or predominantly solid, thyroid nodules
Authors: Celani Marco F. , Mariani Maurizio , Mariani Giuliano
Published: June 2009

The efficacy of levothyroxine suppressive therapy in the treatment of benign solitary thyroid nodules is controversial. In order to investigate this issue further we studied 122 patients with a solitary, solid or predominantly solid, thyroid nodule. The benign (colloid) nature of all nodules was proved by fine-needle aspiration biopsy. At the pertechnetate-99m thyroid scanning 91% of the nodules were "cold" and 9% "warm". All the patients received suppressive oral doses of levothyroxine (0.1 to 0.2 mg/day). Fifty-three patients were treated with levothyroxine for 6 months, 31 for 9 months and 38 for 12 months. The size of each nodule before and after treatment was evaluated by high-resolution ultrasonography. The actual suppression of TSH secretion was monitored at 3-month intervals using an ultrasensitive immunometric assay. At the end of levothyroxine treatment, patients were classified as responders (decrease in nodule volume ≥50%, 68/122 = 55.7%; mean percent change in nodule volume = −77.1 ± 15.7%), partially responders (decrease in nodule volume <50%, 24/122 = 19.7%; mean percent change in nodule volume = −27.5±10.1%), and nonresponders, when either no change in nodule volume (16/122 = 13.1%) or an increase in nodule volume (14/122 = 11.5%) was observed. In each group serum free T4 rose significantly in response to levothyroxine therapy, whereas serum free T3 remained unchanged. TSH levels were undetectable in all patients. Both the proportion of responders, partially responders and nonresponders, and the mean percent decrease in nodule volume in the responder group were not significantly different in patients treated with levothyroxine for 6, 9 or 12 months, respectively. Therefore, it appears that levothyroxine therapy is effective within 6 months in reducing the size of colloid solitary, solid or predominantly solid, thyroid nodules or in preventing their further growth in about 90% of our patients.
Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism
Authors: Giustina Andrea , Ferrari Carlo , Bodini Corrado , Buffoli Maria Grazia , Legati Fabio , Schettino Maurizio , Zuccato Fausto , Wehrenberg William B.
Published: June 2009

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 μg. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pretreatment study. In conclusion, the GH response to GHRH is inhibited and delayed by hyperthyroidism and returns to the normal pattern after long-term euthyroidism has been achieved with methimazole.
Impaired prolactin response to hyperthermia in heroin addicts
Authors: Vescovi P. P. , Pedrazzoni M. , Maninetti L. , Pioli G. , Gerra G. , Passeri M.
Published: June 2009

The response of PRL, FSH and LH to saunainduced hyperthermia was examined in 8 male former heroin addicts (studied after 14-24 days of abstinence) and 8 age- and sex-matched control subjects. The basal levels of PRL tended to be higher in former drug users than in control subjects (p=0.07). After sauna, there were no changes in the addict group, whereas a significant increase was observed in normal subjects (p<0.001). Baseline plasma LH and FSH levels were significantly lower in former drug users (p=0.02), but no change was found after sauna in either group. These findings are consistent with the existence of a deficient adaptation to thermal stress in chronic drug users, even after a relatively short drug-free period.
Effects of a V1-vasopressin antagonist on ACTH release following vasopressin infusion or insulin-induced hypoglycemia in normal men
Authors: Hader Oliver , Bähr Volker , Hensen Johannes , Hofbauer Karl G. , Oelkers Wolfgang K. H.
Published: June 2009

Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 μg/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2±1.6 ng/l (3.8±0.35 pmol/l) to 31.7±4.2 ng/l (7.0±0.92 pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5±1.2 ng/l (3.6±0.26 pmol/l) to 41.8±3.5 ng/l) (9.2±0.77 pmol/l) being significant (p<0.05). Peak plasma cortisol levels were 323±42 and 529±52 nmol/l, respectively (p<0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 μg/kg of the AVP antagonist or placebo, all subjects received 0.12 IU/kg of normal insulin, thus inducing a fall of blood glucose levels below 2 mmol/l. The AVP antagonist caused a moderate but insignificant reduction of the rise in plasma ACTH and a slightly greater, significant reduction of the increment in plasma cortisol (350±19 nmol/l with antagonist and 469±90 nmol/l with placebo, p<0.05) during insulininduced hypoglycemia. The results indicate that a. the AVP antagonist partly inhibits the stimulatory effect of infused AVP on ACTH release in normal men; b. a slightly higher dose of this competitive AVP antagonist inhibits ACTH and cortisol stimulation by hypoglycemia only very little. The importance of AVP as an ACTH-releasing factor in the latter condition may have been underestimated by our experiment, since AVP concentrations in hypophyseal portal blood during hypoglycemia probably were higher than during the AVP infusion experiment.
Lack of effects of hyperglycemia on the disposal of 3-hydroxybutyrate in insulin-dependent diabetic patients
Authors: Møller N. , Jørgensen J. O. L. , Møller J. , Ørskov L. , Pørksen N. , Alberti K. G. M. M. , Schmitz O.
Published: June 2009

There is evidence that hyperketonemia in insulin-dependent diabetes may be aggravated by a decreased disposal rate for ketone bodies. To test the hypothesis that this decrease may be induced by concomitant hyperglycemia through substrate competition at the acetyl-CoA level, 5 young insulin-dependent diabetic subjects received at 2-h iv infusion of 0.9 mmol 3-hydroxybutyrate · kg−1 · h−1 at clamped 1. euglycemia (5 mmol/l) and 2. hyperglycemia (11 mmol/l) on separate occasions. To ensure similar metabolic conditions, a low-dose hyperinsulinemic euglycemic clamp was performed during the 5 h preceding the actual studies. Substrate fluxes in muscle were assessed through the forearm technique. The glucose infusion rate was 4.9 and 2.9 mg· kg−1·min−1, and the forearm arteriovenous difference for glucose was 0.72 during hyperglycemia and 0.39 mmol/l (p<0.05). during euglycemia. Hyperglycemia did not affect circulating levels of free insulin, glucagon, nonesterified fatty acids, 3-hydroxybutyrate (hyperglycemia: 665, euglycemia: 770 μmol/l, p>0.05) or acetoacetate, nor forearm uptake of 3-hydroxybutyrat (hyperglycemia, 152, euglycemia: 168 μmol/l, p>0.05). In conclusion, our results do not suggest any inhibitory role for hyperglycemia in the disposal of ketone bodies. In as much as extrapolation from the present well insulinized state is appropriate, the data indicate that alternative mechanisms may be involved in the observed impairment of ketone body clearance in hyperketonemic insulin-dependent diabetic patients.
Testicular responsiveness to hCG during infancy measured by salivary testosterone
Authors: Dunkel Leo , Huhtaniemi Ilpo
Published: June 2009

To investigate the role of gonadotropins in postnatal testicular activation, testosterone responsiveness to human chorionic gonadotropin was studied in 11 male infants (aged 5-180 days). The boys were given a single im injection of 5000 IU/1.7m2 hCG, and serum and salivary testosterone responses were then measured for 7 days. The results were compared with the serum testosterone responses of 8 older prepubertal boys (aged 1.7-10.4 years) studied with the same protocol. The mean (±sem) basal serum testosterone levels were 2.67±1.27 nmol/l in the infants and 0.09±0.02 nmol/l in the prepubertal boys (p<0.05). Both groups gave a significant response to hCG stimulation (p<0.001, ANOVA, one-way). The stimulated concentrations of serum testosterone were higher in the infants than in the prepubertal boys (p<0.001). The mean basal level of salivary testosterone was 30.5 ±7.0 and the mean maximal level was 97± 10.3 pmol/l in the infants (p<0.001). No age-related changes were observed in either basal or hCG-stimulated levels. In infants the mean (±sem) maximal hCG-stimulated increase was 25 ± 10-fold in serum and 8±4-fold in saliva (p=0.13). A clear stimulatory effect of hCG on testicular testosterone production was found, suggesting that the postnatal increase in serum testosterone concentration in male infants is gonadotropin-mediated. Salivary testosterone concentrations can be increased by hCG, indicating that measurements of salivary testosterone may provide an optional, non-invasive method for assessing gonadal function in children.
Immunological quantitation of rat and mouse thyroxine-binding globulins. Ontogenesis and sex-dependence of the circulating levels of the thyroxine-binding globulins
Authors: Vranckx Roger , Savu Lia , Maya Michelle , Rouaze-Romet Marielle , Nunez Emmanuel A.
Published: June 2009

We describe the preparation of monospecific antisera against a thyroxine-binding globulin partially purified from immature rat sera by affinity chromatography on thyroxine-Sepharose. The antisera are used for the rocket immunoelectrophoresis assay of rat thyroxinebinding globulin and also, owing to their partial crossreactivity with mouse thyroxine-binding globulin, for the quantitation of this serum binding protein in the mouse. The thyroxine-binding globulin is measured in developing rats and in sexually mature male and female rats and mice. The results of the ontogenetic study confirm the postnatal surge of serum thyroxine-binding globulin levels, formerly demonstrated with binding techniques. They allow further to define the correlations, dependent on age, of the immunoquantitated thyroxine-binding globulin and transthyretin levels with the abilities of the sera to bind thyroxine. In sexually mature rats and mice we demonstrate an opposite sexdependence of thyroxine-binding globulin levels, characterized by increased levels of the protein in the female rats versus increased levels of the protein in the male mice. This is the first report of immunological quantitation of rat and mouse thyroxine-binding globulins.
Antidiuretic effect of indapamide in central diabetes insipidus
Authors: Koçak Mustafa , Karademir Bülent Mustafa , Tetiker Tamer
Published: June 2009

Indapamide produced a significant decrease in urinary output in three patients with central diabetes insipidus. The 24-h urinary volume was reduced from 5 to 2.3 1 in a 39-year-old woman; from 11 to 4.3 1 in a 30-year-old man, and from 16 to 9.2 1 in a 40-year-old man receiving 2.5 mg of indapamide per day. To our knowledge, the antidiuretic effect of indapamide in central diabetes insipidus has not been reported previously.
Basal and saline-stimulated plasma atrial natriuretic hormone in Cushing's syndrome
Authors: McKnight J. A. , McCance D. R. , Roberts G. , Sheridan B. , Atkinson A. B.
Published: June 2009

The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43±4 years (mean±sem). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 2 1 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0±0.9 pmol/l in Cushing's subjects and 6.9±2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3±3.9 vs 10.4± 1.9 pmol/l; p<0.05). Serum aldosterone and plasma renin activity were not different between groups. Mean blood pressure was higher in patients (114±4 vs 91±7 mmHg; p<0.05). Urinary sodium excretion was not different between groups before saline, but during the four hours of saline was higher in Cushing's subjects (133±12 vs 67±11 mmols; N=6; p<0.05). Our results suggest that during salt loading the exaggerated natriuresis seen in the Cushing's group may have been caused by ANH.
Thyroid volume and goitre prevalence in the elderly as determined by ultrasound and their relationships to laboratory indices
Authors: Hintze Gerhard , Windeler Jürgen , Baumert Jörg , Stein Herbert , Köbberling Johannes
Published: June 2009

In 569 unselected elderly subjects over 60 years from the general population of an iodine-deficient area, a palpation and an ultrasound investigation of the thyroid were performed. Additionally, thyroid hormone values were determined in 466 of the 569 subjects (81.9%) and urinary iodine excretion in 491 subjects (86.3%). By palpation, no thyroid enlargement was noticed in 302 subjects (54.2%), goitre Ia in 98 (17.6%), goitre lb in 94 (16.9%), goitre II in 53(9.5%), and goitre III in 10(1.8%). The thyroid volumes (medians) by ultrasound were 18.6 ml in the entire group, in women (N=489) 19.2 ml, and in men (N=80) 16.6 ml. One hundred and one subjects had a thyroid nodule (17.6%), 43 persons cystic lesions (7.6%). If, according to the literature, a goitre is defined as a thyroid enlargement of more than 18 ml in women and more than 25 ml in males, a goitre prevalence of 54.2% in females and of 22.5% in males was obtained. The goitre prevalence in the entire group was calculated as 49.7%. Thyroid hormone measurements showed in subjects with goitre a significant lower TSH value (p<0.001) and a higher thyroglobulin value (p<0.001). In summary, the study shows a high prevalence of goitre in elderly subjects, a high prevalence of nodules in these thyroids, a negative correlation of goitre volume with TSH, and a positive correlation of goitre volume with the thyroglobulin concentration.
Effects of ketoconazole in hirsute women
Authors: Akalin Sema
Published: June 2009

To determine the efficacy of ketoconazole in the treatment of hirsutism, clinical and hormonal effects of this agent were evaluated with a randomized, placebocontrolled, double-blind cross-over study design. Nine hirsute women were given ketoconazole (600 mg/day) or placebo for 6 months and then crossed over. The severity of hirsutism was assessed according to the scale of Ferriman & Gallwey. Baseline serum testosterone, dehydroepiandrosterone sulphate, progesterone, estradiol, basal and stimulated cortisol and 17-alpha hydroxyprogesterone were measured. Blood was also drawn for FSH and LH levels at 0, 30, 60, and 90 min of a GnRH stimulation test. The same parameters were determined following administration of placebo or ketoconazole for 6 months. The pretreatment (28.3±0.9) and post-placebo (27.7±1.4) Ferriman-Gallwey scores were significantly higher than the post-ketoconazole score (16.6±1.3, p≤0.01). Basal and stimulated cortisol levels were not blunted after ketoconazole, but basal and stimulated 17-hydroxyprogesterone levels were significantly higher, indicating sufficient enzymatic inhibition. Serum dehydroepiandrosterone sulphate and testosterone levels were significantly lowered following ketoconazole (p≤0.05). Although E2 levels did not change significantly at any time, E2:testosterone ratios were significantly higher after ketoconazole (p≤0.01), and the LH:FSH area ratio was also significantly greater than 3 after ketoconazole. It is concluded that ketoconazole significantly alleviates hirsutism by inhibiting steroid synthesis.
Pituitary function in thalassemic patients and the effect of chelation therapy
Authors: Vannasaeng Sathit , Fucharoen Suthat , Pootrakul Pensri , Ploybutr Sirirat , Yansukon Pornpun
Published: June 2009

This study examined anterior pituitary function and the effect of chelation therapy in 31 patients with β-thalassemia/HbE disease. Patients were divided into those receiving chelation therapy by deferoxamine and those receiving no such therapy (control group). Pituitary function studies were repeated in both groups 18 months later. The results showed decreased pituitary responses following stimulation in 22 patients. Among these, gonadotropin and PRL responses were most affected. After 18 months, serum ferritin levels had significantly decreased in the deferoxamine group. PRL and GH responses were improved in 3 patients receiving chelation therapy without changes in other hormone responses. In contrast, no changes in pituitary responses were shown in the control group at the end of follow-up. There were 6 drop-outs (4 in the control and 2 in the deferoxamine group) and 3 deaths (2 in the control and 1 in the deferoxamine group) during 18 months. In conclusion, gonadotropin and PRL deficiencies occur most frequently in thalassemic patients. Chelation therapy for 18 months markedly reduced serum ferritin level and might preserve or improve PRL and GH secretions, but seems to have no beneficial effects on other pituitary hormone reserves.
Impaired secretion of growth hormone-releasing hormone, growth hormone and IGF-I in elderly men
Authors: Bando Hiroshi , Zhang Chenyu , Takada Yukinobu , Yamasaki Ryuichi , Saito Shiro
Published: June 2009

The GHRH test and L-dopa test were performed in 12 normal young men (24.1 ± 1.1 years) and 12 normal elderly men (77.8±1.4 years) to investigate age-related changes in secretion of GHRH, GH and IGF-I. The basal plasma levels of GHRH and GH were not significantly different in young and elderly men, but the basal plasma level of IGF-I was higher in the young men (159.0± 11.7 vs 86.7± 11.6 μg/1). The area under the curve for plasma GH in the GHRH test was less in the elderly group (35.1 ±5.9 vs 11.2 ± 2.1 μg · h−1 · 1−1, p<0.001). The AUCs for the plasma GHRH and GH responses in the L-dopa test in young and elderly men were 32.0±2.7 vs 20.3±1.8 ng · h−1 · 1−1 (p<0.001), and 21.8±4.6 vs 5.4±1.1 μg · h−1 · 1 (p<0.01), respectively, indicating decreased releases of GHRH and GH in the elderly. Correlations between the AUCs for plasma GHRH and GH responses in L-dopa were found in both groups, but the ratio of the AUCs for GH/GHRH was lower in the elderly group. The elderly group showed a significant correlation between the basal plasma IGF-I level and the AUCs for plasma GH in the GHRH and L-dopa tests. These results suggest that elderly men have a decreased reserve of hypothalamic GHRH, resulting in secondarily impaired GH release, which may lead to a lower level of IGF-I than in young men.
Amyloid protein in somatostatinoma differs from human islet amyloid polypeptide
Authors: Ohsawa Haruhiko , Kanatsuka Azuma , Tokuyama Yoshiharu , Yamaguchi Takahide , Makino Hideichi , Yoshida Sho , Horie Hiroshi , Mikata Atsuo , Kohen Yoshibumi
Published: June 2009

Amyloid deposits in somatostatinomas are rare observations. To examine the characteristics of this amyloid, we compared amyloid deposits in a somatostatinoma to those found in pancreatic tissue in patients with Type II diabetes mellitus and in insulinomas, using immunohistochemical techniques and specific antibodies to islet amyloid polypeptide or other pancreatic hormones, as well as electron-microscopy. Antibodies to islet amyloid polypeptide regions 8-17 or 25-37 were confirmed to be specific. Amyloid deposits in patients with Type II diabetes mellitus and in insulinomas, but not those in the somatostatinoma strongly reacted with these antibodies, or to an antibody to amyloid P component. Amyloid deposits in the somatostatinoma were not reactive with antibodies to somatostatin or to other pancreatic hormones. Electron-microscopic examinations revealed that amyloid fibrils in the somatostatinoma were thinner and more randomly distributed than were those in islets from patients with Type II diabetes mellitus. As amyloid in somatostatinomas is unlike that consisting of islet amyloid polypeptide or other mature pancreatic hormones, it may be a novel type of local amyloid in pancreatic islets.
Vasoactive intestinal polypeptide stimulates parathyroid hormone release by interaction with cyclic adenosine monophosphate production of bovine parathyroid cells
Authors: Joborn Henrik , Larsson Rolf , Rastad Jonas , Nygren Peter , Åkerström Göran , Ljunghall Sverker
Published: June 2009

Influence of vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and substance P was investigated on dispersed parathyroid cells of adult cattle. At a physiological concentration of extracellular calcium, vasoactive intestinal polypeptide stimulated the parathyroid hormone release in a dose-dependent manner, whereas no effects were noted for the other peptides. The dependency of PTH secretion upon extracellular calcium was shifted to the right by vasoactive intestinal polypeptide at 10−6 mol/l, with a tendency for greater effects at low (0.5 mmol/l) than high concentrations (2.0-3.0 mmol/l) of the cation. Vasoactive intestinal polypeptide significantly enhanced cAMP release of the parathyroid cells, whereas no influence was noted on cytoplasmic calcium or pH within the cells. The results suggest that vasoactive intestinal polypeptide stimulates the PTH release by interaction with cAMP production of the parathyroid cells. This effect may contribute to the development of hypercalcemia in patients with neuroendocrine tumours secreting vasoactive intestinal polypeptide.
Effects of interleukin 1 on growth and adenosine 3',5'-monophosphate generation of the rat thyroid cell line, FRTL-5 cells
Authors: Zeki Kazuya , Azuma Hiroyuki , Suzuki Hidero , Morimoto Isao , Eto Sumiya
Published: June 2009

We investigated the effects of IL-1, IL-2, IL-6, interferon-γ and tumour necrosis factor-α on growth and cAMP generation of FRTL-5 cells. IL-1 produced a significant stimulation of [3H]thymidine incorporation into FRTL-5 cells without TSH, whereas IL-1 caused significant reductions in [3H]thymidine incorporation induced by TSH or forskolin, which is known as an adenylate cyclase activator. Intracellular cAMP generation of FRTL-5 cells was stimulated by IL-1, whereas TSH-stimulated cAMP generation was inhibited by IL-1. These effects of IL-1 was neutralized by addition of anti-IL-1 antibody. The studies suggested that IL-1 blocks the effects of TSH on proliferation and cAMP generation of FRTL-5 cells on a post-receptor site of TSH.
Intracellular calcium and phospholipid turnover are not involved in the inhibition of iodothyronine 5'-deiodinase type II activity by T4
Authors: Juge-Aubry Cristiana , Dôme Pierre , Siegrist-Kaiser Catherine A. , Capponi Alessandro M. , Burger Albert G.
Published: June 2009

In glial cell cultures, iodothyronine 5'-deiodinase type II is stimulated by dibutyryl cAMP. Serum-free medium increases enzyme activity and prolongs the half-life of the enzyme. T4 and rT3 specifically inhibit this activity. We tested whether enzyme inactivation by T4 was mediated by changes in cytosolic free calcium concentration and/or phospholipid turnover. Intracellular calcium concentration was decreased either by chelation of extracellular calcium or by chelation of extracellular and intracellular calcium. Neither basal hypothyroid 5'-deiodinase activity nor its inactivation by T4 were modified in such experimental conditions, compared with control cells incubated in normal calcium-containing medium. T4 by itself had no effect on the cytosolic free calcium concentration for up to 20 min. Studies on phospholipid turnover included norepinephrine in parallel to T4 as positive stimulation control. While norepinephrine clearly accelerated phosphoinositide turnover, there was no effect of T4 on any phospholipid turnover. These results suggest that neither cytosolic free calcium nor phospholipid turnover is involved in T4-dependent modulation of 5'-deiodinase type II activity in astrocytes in culture.
Effect of lithium chloride on testicular steroidogenesis and gametogenesis in immature male rats
Authors: Ghosh P. K. , Biswas N. M. , Ghosh D.
Published: June 2009

The present study was performed on immature male rats aged 35 days. Subcutaneous injections of lithium chloride at a daily dose of 2.0 mg/kg for 15 days resulted in significant inhibition of spermatogenesis at stage VII of the seminiferous epithelial cycle. Spermatogonia A, preleptotene spermatocytes and step 7 spermatids were decreased in number in comparison to controls. Serum levels of FSH, LH, PRL, and testosterone were decreased. Activities of testicular Δ5-3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were suppressed along with a low caudal epididymal sperm count in comparison with controls. When the treatment was prolonged for 20 and 25 days, it showed an additional significant diminution in accessory sex organ weights and number of midpachytene spermatocytes at stage VII in comparison to control animals of corresponding age. It is concluded that lithium has an adverse effect on testicular function in immature rats by reducing serum levels of FSH, LH, PRL, and testosterone. Furthermore, since hormonal changes and altered spermatogenic activities were evident when the serum concentration of lithium was within the therapeutic range, our data may have some potential clinical implications.
Effects of triiodothyronine, dexamethasone and estradiol-17β on GH mRNA in rat pituitary cells in culture as revealed by in situ hybridization
Authors: Martinoli M. G. , Veilleux R. , Pelletier G.
Published: June 2009

The GH lines of rat pituitary tumour cells have been largely used to study the regulation of GH mRNA. In order to investigate the role of T3, dexamethasone and estradiol-17β on GH expression in non-tumoural pituitary cells, we have used in situ hybridization techniques performed on rat anterior pituitary cells in monolayer culture. The amounts of mRNA encoding for GH, as evaluated by counting the number of grains per somatotrope, were markedly reduced after 4 days of culture in a steroid-free medium supplemented with an hypothyroid calf serum. Addition of T3 or dexamethasone for 3 days increased GH mRNA levels. The concomitant administration of the two hormones produced a synergistic effect on GH mRNA levels which became higher than those observed after T3 or dexamethasone administration alone. However, this effect did not restore GH mRNA levels to those measured in monolayer pituitary cells grown in medium containing 10% fetal calf serum. Moreover GH mRNA levels appeared higher in male than in female pituitary cells. The administration of E2 to pituitary cell cultures from both male and female rats produced an increase by 15, and 12.8% in GH mRNA levels in male and female, respectively. This stimulatory effect of E2 in cell culture was competitively blocked by simultaneous incubation with the antiestrogen LY156758 (Keoxifene). These results demonstrate that T3, dexamethasone as well as E2 act directly on somatotropic cells to regulate GH gene expression.
Sexual dimorphism in renal function and hormonal status of New Zealand genetically hypertensive rats
Authors: Ashton N. , Balment R. J.
Published: June 2009

Renal water and electrolyte handling and related plasma hormone levels were measured in male and female New Zealand genetically hypertensive and normotensive rats, in an attempt to etablish any potentially important sex-related differences in these parameters. Male hypertensive rats had higher blood pressure than female hypertensive rats, but normotensive rats showed no such sex difference. Both groups of males had higher fluid turnover rates than respective females, and this was associated with raised plasma vasopressin in hypertensive males. Female hypertensive rats excreted more sodium, potassium and chloride in association with lower plasma aldosterone and higher corticosterone levels compared with the other groups. Plasma electrolytes did not differ between the four groups, but plasma osmolality was higher in hypertensive than normotensive rats of both sexes. A higher rate of electrolyte loss and lower fluid turnover in association with reduced plasma vasopressin may contribute to the lower blood pressure of female compared with male hypertensive rats.