bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory actions of interleukin-1β on steroidogenesis in primary cultures of neonatal rat testicular cells
Authors: Fauser Bart C. J. M. , Galway A. Brenda , Hsueh Aaron J. W.
Published: December 2008

Abstract. Interleukin-1 is an important cytokine produced by activated macrophages. Because macrophages have been localized in the testis and interleukin-1 bioactivity has been observed in the testis, the potential effect of interleukin-1 on gonadotropin-stimulated androgen production was investigated using primary cultures of neonatal rat testis cells. Cells were incubated for 3 days before change of medium and treatment with human chorionic gonadotropin and interleukin-1. After 3 additional days medium testosterone and progesterone levels were determined. Human chorionic gonadotropin treatment (0.30–30 μg/l) of cultured cells stimulated testosterone production dose-dependently with a maximum increase > 18-fold over control values. Although interleukin-1 treatment alone did not affect testosterone production, the concomitant addition of interleukin-1 β (0.5–5 × 103 U/l) caused a dose-dependent decrease of human chorionic gonadotropin action, with 50% inhibition occurring at 1.4 × 103 U/l (0.6 × 10−11 mol/l; N = 5 experiments). Interleukin-1β also inhibited forskolin- and dibutyryl cAMP-stimulated testosterone production. The suppression of human chorionic gonadotropin-induced testosterone production by testis cells was accompanied by increased (>3-fold) progesterone levels. Moreover, the conversion of exogenously added androgen precursors (progesterone and 17α-hydroxyprogesterone) to testosterone by human chorionic gonadotropin-stimulated cells was suppressed by interleukin-1β suggesting that the activity of the 17α-hydroxylase enzyme may be decreased. The present study shows that interleukin-1β is a potent inhibitor of androgen biosynthesis by rat testiscular cells in culture and it can be hypothesized that this cytokine may play intratesticular paracrine roles.
D-glucose uptake is increased in jejunal brush-border membrane vesicles from hyperthyroid chicks
Authors: Debiec Hanna , Cross Heide S. , Peterlik Meinrad
Published: December 2008

Abstract. Jejunal brush-border membrane vesicles were harvested from 4-week old chicks whose thyroid status had been altered either by a daily injection of 20 μg T3 for 1 week or which through the preceding 4 weeks had received propylthiouracil and than had been repleted with either 20 or 80 μg T3 in divided doses within 48 h. T3 markedly stimulated D-glucose uptake in brush-border membrane vesicles in the presence of an outside/inside (100/0 mmol/l) Na+ gradient. T3 administration had no detectable influence on the Na+ permeability of the isolated vesicles. The effect of the thyroid hormone on Na+ gradient-driven D-glucose uptake was fully preserved at zero transmembrane potential difference. These findings exclude that T3 stimulates Na+-dependent D-glucose transport in the small intestine through changes of the electrochemical Na+ gradient or through alteration of the transmembrane potential difference. Tracer exchange experiments under equilibrium and voltageclamp conditions revealed a significantly shorter halftime of D-glucose uptake in brush-border membrane vesicles from T3-treated chicks. Kinetic analysis showed that T3 administration significantly increases the apparent maximal velocity of D-glucose transport in brushborder membrane vesicles, whereas the apparent Km values were virtually unaltered. From these data we conclude that T3 increases the activity of Na+-dependent D-glucose carriers in the brush-border membrane. This is interpreted as consistent with a greater rate of D-glucose absorption from the intestinal lumen under conditions of hyperthyroidism.
Studies on the occurrence of ophthalmopathy in Graves' disease
Authors: Marcocci C. , Bartalena L. , Bogazzi F. , Panicucci M. , Pinchera A.
Published: December 2008

Abstract. Eye disease was associated with hyperthyroidism in 202 of 221 patients with active Graves' ophthalmopathy (91.4%) and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in the remaining 19 (8.6%). All the latter patients had some mild thyroid abnormalities (thyroid autoantibodies, negative TRH test, negative T3 suppression test, goitre). Sex distribution analysis evidenced a higher prevalence in females with a female/male ratio of 2.1 which was, however, significantly lower (P < 0.05) than that observed in control (Graves' disease patients without overt ophthalmopathy (female/male ratio = 3.4)). Patients with euthyroid Graves' disease showed a female/male ratio of 0.7. Age distribution revealed a peak prevalence in the 5th decade of life, identical to that of Graves' disease without ophthalmopathy. A close temporal relationship between the onset of hyperthyroidism and the onset of ophthalmopathy was found, since in about 85% of the patients the first ocular manifestations occurred within ±18 months around the onset of hyperthyroidism.
Turner's syndrome: treatment of 203 patients with recombinant human growth hormone for one year
Authors: Takano Kazue , Shizume Kazuo , Hibi Itsuro , _ _
Published: December 2008

Abstract. A total of 203 patients with Turner's syndrome were treated with three different kinds of recombinant hGH preparations for one year. One hundred and seven patients were treated with hGH at a weekly dosage of 0.5 IU/kg, 71 with 1.0 IU · kg−1 · week−1, and the remaining 25 patients with combined administration of 0.5 IU · kg−1 · week−1 hGH and a small amount of anabolic steroid. All three treatment groups showed statistically significant growth increases during the treatment. Fifty percent of the patients treated with 0.5 IU · kg−1 · week−1 and 80% of the patients treated with 1.0 IU · kg−1 · week−1 showed growth rates more than 2 cm per year greater than pretreatment values or beyond the second sd of the untreated growth rate. Plasma somatomedin C levels were elevated and no remarkable advances in bone age were observed during the treatment. Antibody against hGH was observed in 71.4% and 10.8% of the methionylhGH and methionine-free-hGH treated patients, respectively. However, the antibodies did not suppress the growth promoting effect of methionyl-hGH. Otherwise, there were no significant changes in physical or laboratory examinations. No glucose intolerance was observed. These results indicate that hGH treatment is useful for the acceleration of growth velocity in patients with Turner's syndrome.
Lack of correlation of serum estradiol with growth velocity during male pubertal growth
Authors: Belgorosky A. , Martinez A. , Heinrich J. J. , Rivarola M. A.
Published: December 2008

Abstract. The adolescent growth spurt in boys is under hormonal control. It is accepted that androgens and growth hormone contribute to male pubertal growth, but the role of estrogens is uncertain even though low-dose estradiol administration stimulates growth in prepubertal boys. In the present work, the correlation of serum testosterone and serum estradiol with growth velocity was studied in 16 pubertal normal boys. The study included correlations of growth velocity with serum nonsex hormone-binding globulin-bound testosterone and with serum nonsex hormone-binding globulin-bound estradiol, which are parameters of serum bioavailable sex hormones. A statistically significant positive correlation was found between serum testosterone and growth velocity but not between serum estradiol and growth velocity. These findings are against the hypothesis that estrogens play a growth promoting role during male puberty.
Pyridostigmine counteracts the blunted growth hormone response to growth hormone-releasing hormone of obese children
Authors: Loche S. , Pintor C. , Cappa M. , Ghigo E. , Puggioni R. , Locatelli V. , Müller E. E.
Published: December 2008

Abstract. We have evaluated the effect of acute administration of pyridostigmine bromide, a cholinesterase inhibitor, on the GHRH-induced GH rise in 11 obese children and in 8 age-matched controls. The GH response to GHRH (hpGRF 1–40, 1 μg/kg iv), evaluated both as maximum GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with pyridostigmine bromide (60 mg orally 60 min before the GHRH injection) significantly increased both baseline GH levels and the GH response to GHRH in all the obese subjects, so that their mean baseline GH, peak GH levels and integrated area under the curve after pyridostigmine bromide plus GHRH were similar to those of the control children after GHRH. Also in control children pyridostigmine bromide increased (though not significantly) baseline GH levels, and caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after pyridostigmine bromide plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Mean baseline Sm-C levels were significantly higher in the obese than in control children. These data show that enhancement of cholinergic neurotransmission, likely in the hypothalamus, counteracts the blunted GH response to GHRH present in the obese children, and that in simple obesity the potential of the pituitary to make a secretory response to a direct GH secretagogue is preserved.
A monthly cycle during third trimester pregnancy in the serum concentrations of progesterone and aldosterone and the urinary excretion rate of potassium
Authors: Paaby Per , Nielsen Aage , Raffn Kjeld
Published: December 2008

Abstract. Eleven healthy women were examined three times a week during the third trimester. A mathematical model (parabolas overlaid with a cosine curve and containing parameters for cycle length, cycle amplitude and phase) was used in a multivariate analysis of changes in serum progesterone, serum aldosterone, serum osmolality and urinary potassium. A highly significant monthly cycle in progesterone and aldosterone and a significant cycle in the urinary excretion rate of potassium were found. The individual rates of increase in serum progesterone and serum aldosterone were different and uncorrelated, and in the monthly cycle there was a phase difference between them. We think that the changes in serum progesterone and serum aldosterone are controlled by different stimuli and that the control of the cyclical component originates in the maternal neuro-endocrine system.
Estradiol and progesterone levels in the endometrium and the reproductive tract luminal washing during the pre-implantation stages of gestation in the rhesus monkey
Authors: Ghosh D. , Sengupta Jayasree
Published: December 2008

Abstract. To obtain an understanding of the sex steroid hormonal milieu during early gestation, the concentrations of estradiol-17β and progesterone were measured in endometria and reproductive tract luminal fluids collected during the post-ovulatory period (days 2 to 6) of conception, and of non-mated menstrual cycles of the rhesus monkey (Macaca mulatta). Estradiol content was found to be higher (P< 0.05) in endometria obtained from conception cycles; day-wise analysis revealed higher (P< 0.05) level of tissue estradiol concentration on day 6 of post-ovulation as compared with the normal menstrual cycle. Endometrial progesterone content remained, however, unaltered in both groups of monkeys and thus relatively lower (P< 0.05) endometrial progesterone to estradiol ratios were seen on days 4, 5 and 6 of gestation compared with normal menstrual cycle. There were no significant changes in the profiles and concentrations of estradiol and progesterone in luminal washings. The typical sex steroid hormonal milieu observed in the endometrium during the peri-implantation stage of gestation in conception cycle may be related to the endometrial differentiation towards implantation in the rhesus monkey.
Role of prolactin in age-related change in serum dehydroepiandrosterone sulphate concentrations
Authors: Yamaji Tohru , Ishibashi Miyuki , Takaku Fumimaro , Teramoto Akira , Takakura Kintomo , Takami Masami , Fukushima Takanori , Kamoi Kyuzi
Published: December 2008

Abstract. Serum dehydroepiandrosterone sulphate concentrations were measured in 70 patients with prolactinoma and in 54 patients with acromegaly with normal adrenocortical function. Compared with values in normal subjects of corresponding age, serum dehydroepiandrosterone sulphate levels were increased in 22 patients with prolactinoma (31%) and in 5 patients with acromegaly (9%). The four acromegalic patients who had elevated serum dehydroepiandrosterone sulphate levels had hyperprolactinemia. The mean serum dehydroepiandrosterone sulphate concentrations in patients with prolactinoma in each decade decreased with advancing age. There was a significant negative correlation between serum dehydroepiandrosterone sulphate concentrations and ages of the patients with prolactinoma. In all 8 women with prolactinoma as in 6 normal women, serum dehydroepiandrosterone sulphate levels declined definitely during the 9 years of follow-up despite persistent hyperprolactinemia. These results indicate that serum dehydroepiandrosterone sulphate levels are increased in a substantial number of patients with hyperprolactinemia, however, PRL per se may not play a significant role in the age-related change in serum dehydroepiandrosterone sulphate levels.
Suppression of prolactin release and mRNA accumulation by two novel dopamine agonist agents
Authors: Davis Julian R. E. , Vidal Maria E. , Wilson Elizabeth M. , Sheppard Michael C.
Published: December 2008

Abstract. Two novel dopamine agonist drugs, CV 205–502 and CQP 201–403, have been investigated to compare their effects on prolactin secretion and prolactin mRNA accumulation in cultured rat pituitary cells. Both drugs gave dose-dependent suppression of prolactin release over a 24 h incubation period: when each drug was used at 100 nmol/l CV 205–502 and CQP 201–403 induced suppression to 8.9 ± 1.7 and 10.2 ± 1.8% of control release, respectively, compared to 26.7 ± 4.8% of control with 100 nmol/l bromocriptine. There was no consistent effect on growth hormone release. Cytoplasmic accumulation of prolactin mRNA was also inhibited by both drugs at this concentration, to 50.2 ± 5.5% of control values by CV 205–502 and to 67.4 ± 8% of control by CQP 201–403, and to a similar extent by 100 nmol/l bromocriptine (50.6 ± 9.1% of control). None of the drugs had any significant effect on GH mRNA levels. These data suggest that the agents exert their effect at a pretranslational stage of prolactin synthesis, as well as at the level of hormone release.
Interactions between cholinergic agonists and enteric factors in the regulation of insulin secretion from isolated perifused rat islets
Authors: Zawalich Walter S. , Zawalich Kathleen C. , Rasmussen Howard
Published: December 2008

Abstract. The ability of the cholinergic agonist carbachol to sensitize islets to the action of combined glucose, cholecystokinin and gastric inhibitory polypeptide was determined in isolated rat islets. In response to this combination, peak first phase insulin secretion from control islets averages 85 ± 5 pg · islet−1 · min−1 (mean ± sem) and the insulin secretory rates measured 35–40 min after the onset of stimulation averages 127 ± 34 pg · islet−1 · min−1. A prior 20 min exposure to 1 mmol/l carbachol potentiates the modest insulin stimulatory response to this combination of stimulants: peak first phase release is 354 ± 61 pg · islet−1 · min−1, and release measured 35–40 min after the onset of stimulation is 179 ± 34 pg · islet−1 · min−1. This sensitizing effect of carbachol lasts for at least 40 min and can be duplicated by the natural in vivo agonist acetylcholine. These results demonstrate that cholinergic stimulation of isolated islets primes them to the subsequent stimulatory effect of a moderate increase in the circulating glucose level and to several postulated incretin factors. If operative in vivo, this communications network between cephalic and enteric factors represents a remarkable control system to ensure the release of insulin in amounts commensurate to meet the anticipated and actual insulin requirements for insulin-mediated fuel disposition.
Study on background factors associated with impaired glucose tolerance and/or diabetes mellitus
Authors: Umeki Shigenobu , Hisamoto Nobumi , Hara Yoshito
Published: December 2008

Abstract. In a cross-sectional health screening 636 persons with negative urine glucose, a 75-g-oral glucose tolerance test was perfomred. We report the clinical features of the subjects with impaired glucose tolerance or diabetes mellitus. In 96 subjects with impaired glucose tolerance, the frequencies of alcohol dependency, fatty liver, and of increased levels of serum uric acid, cholesterol, triglycerides, total serum protein and γ-glutamyl transpeptidase were significantly higher than in normal subjects. In 37 subjects with diabetes mellitus, the frequencies of fatty liver, hypertension and of increased erythrocyte sedimentation rate, triglycerides and γ-glutamyl transpeptidase were significantly higher than in normal subjects. In addition, significant increases in serum γ-glutamyl transpeptidase, triglycerides, serum total cholesterol and body mass index, and a significant decrease in high density lipoprotein cholesterol were also observed in subjects with impaired glucose tolerance and diabetes mellitus. These results suggest that alcohol dependency, fatty liver, obesity and hyperlipidemia are important concomitants of impaired glucose tolerance.
Gonadotropin-releasing hormone agonist inhibits physiologic ovarian follicular loss in rats
Authors: Ataya Khalid , Tadros Magdy , Ramahi Alfida
Published: December 2008

To study the effect of long-term use of GnRH agonists on the number and size distribution of ovarian follicles, two experiments were performed on adult female rats. Treatment was continued for 52 days in Experiment 1 and for 229 days in Experiment 2. Every sixteenth section from one ovary of each rat was examined using a light microscope attached to a BioQuant image analysis computer system. In Experiment 3, control and previously treated rats were mated with known male breeders and the number and normalcy of the offspring evaluated. The results indicate that in rats treated with GnRH agonist: 1) the total number of follicles, the number and percentage of follicles less than 35 μm in diameter were significantly higher than in the control group; 2) the number and percentage of follicles greater than 50 μm in diameter were significantly lower than control; and 3) the number of rats that got pregnant and the litter size were not significantly different from control. We conclude that GnRH agonists inhibit the physiologic process of follicle recruitment and loss and that fertility is preserved after long-treatment administration of GnRH agonists.
Endocrine abnormalities in patients with adrenal tumours incidentally discovered on computed tomography
Authors: Virkkala Anu , Välimäki Matti , Pelkonen Risto , Huikuri Kauko , Kahri Arvi , Kivisaari Leena , Korhonen Timo , Salmi Jorma , Seppälä Pentti
Published: December 2008

To determine endocrine activity of adrenal tumours incidentally discovered on CT, we examined 20 consecutive patients. They underwent thorough hormonal assessment and scintigraphic scanning with radioactive cholesterol under dexamethasone suppression (19 patients). Biochemical findings compatible with cortisol hypersecretion were detected in 5 patients. One patient had reduced reserves of cortisol secretion and one had hyporeninemic hypoaldosteronism. The scintigraphy showed no uptake in 10, unilateral uptake in 4, and bilateral uptake in 5 patients. In 3 patients the finding was unilateral on CT, but bilateral on scintigraphy. Signs of autonomous cortisol production were more common among patients who had uptake on scintigraphy. At the operation of 8 patients only benign lesions were found. During the follow-up (9 to 49 months) of the 12 unoperated patients, the tumour disappeared in one and remained unchanged in the others. No changes occurred in the biochemical findings except in one patient whose cortisol response to 1 mg of dexamethasone became abnormal. Since slight hypercortisolism or a bilateral disease often exists behind an incidentally discovered adrenal tumour, we emphasize the importance of careful assessment of cortisol metabolism and a scintigraphic scanning under dexamethasone suppression in the examination of these patients.
Insulin-like growth factor I increases glomerular filtration rate and renal plasma flow in man
Authors: Guler Hans-Peter , Eckardt Kai-U. , Zapf Jürgen , Bauer Christian , Froesch E. Rudolf
Published: December 2008

Recombinant IGF-I was infused sc at a dose of 20 μg · kg−1 · h−1 to 2 healthy subjects during a total of 79 h. Serum levels of IGF-I rose from 93 and 177 to 502 and 616 μg/l, respectively. Fasting blood glucose remained normal. During the infusion, glomerular filtration rate increased by 31% in subject No. 1 and by 32% in subject No.2. Concomitantly, renal plasma flow increased by 26% and 22%, respectively. Proximal and distal tubular reabsorption of fluid and sodium as determined by lithium clearance was elevated to a similar extent. When determined again one week after the end of the IGF-I infusion, all parameters of renal function had returned to baseline. Sodium excretion, body weight and blood pressure did not change. We conclude that IGF-I infused at pharmacological doses has marked effects on kidney function. Future studies will be necessary to define the clinical potential of recombinant IGF-I in the treatment of diseases characterized by impaired renal perfusion and filtration.
Expression of insulin-like growth factor receptors in primary human thyroid neoplasms
Authors: Yashiro Tohru , Ohba Yoshito , Murakami Hitomi , Obara Takao , Tsushima Toshio , Fujimoto Yoshihide , Shizume Kazuo , Ito Kunihiko
Published: December 2008

The presence of IGF-I receptors was demonstrated in normal and neoplastic tissues of human thyroid. Binding of [125I]IGF-I to thyroid membranes was dependent on time and temperature of incubation, and maximal binding was achieved at 4°C and 18 h of incubation. [125I] IGF-I binding was dose-dependently displaced by unlabelled IGF-I; half-maximal inhibition occurred at concentrations of 10–20 μg/l. IGF-II and insulin had relative potencies of 5 and 1% compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with high affinity (Ka: 1.2–8.6 × 109 1/mol) in normal thyroid tissues. Affinity cross-linking and autoradiography demonstrated the type I IGF receptors. Specific binding of [125I] IGF-I in thyroid cancer tissues (9.69 ± 2.07% per 200 μg protein; mean ± sem, N = 8) was significantly (p <0.05) higher than that in the surrounding normal tissues (3.03 ± 0.35%, N = 8). In contrast, there was no difference in the binding between adenoma tissues (4.19 ± 0.53%, N = 5) and the adjacent normal tissues (2.94 ± 0.24%, N = 5). The higher IGF-I binding in cancer tissues was due to an increase in the binding capacity without any change in the affinity. The presence of IGF-I receptors suggests a possible role of IGF-I and its receptors in the growth of thyroid cancer cells.
Interleukin 1 induces new protein formation in isolated rat islets of Langerhans
Authors: Helqvist Steffen , Hansen Birgit Sehested , Johannesen Jesper , Andersen Henrik Ullits , Nielsen Jens Høiriis , Nerup Jørn
Published: December 2008

It is hypothesized that interleukin 1 induces toxic free radical formation in pancreatic beta-cells leading to beta-cell degeneration and destruction. Therefore, isolated rat pancreatic islets were examined for interleukin 1 and heat shock induced proteins. After exposure to human interleukin 1β (0.015 to 10 μg/1) or heat (40°C) for up to 24 h, islets were labelled with 35S-methionine and solubilized. Islets proteins were analysed by SDS-polyacrylamide gel electrophoresis. By autoradiography it was shown that both interleukin 1 and heat exposure induced the formation of a 70 kD protein. Further, interleukin 1 induced the formation of two proteins of 32 and 80 kD, respectively, which was not seen after heat exposure. Possibly, the 70 kD protein is a member of the heat shock protein 70 family, participating in unspecific cellular defence and maybe free radical scavenging. Other candidates are the superoxide radical scavenging enzyme manganous superoxidedismutase, MHC class II molecules, and heme oxygenase.
Insulin-like growth factor I binding proteins in dairy cows, calves and bulls
Authors: Ronge Harald , Blum Jürg W.
Published: December 2008

Our objective was to measure relative amounts and distributions of serum IGF-I binding proteins and concentrations of hormones and metabolites in dairy cows during the dry period and during lactation, as well as in calves and in growing bulls. Concentrations of IGF-I were lower in cows during lactation than during the dry period. Concentrations of IGF-I, growth hormone, insulin, T3, T4 and glucose were higher in calves and bulls as compared with cows, whereas concentrations of non-esterified fatty acids, urea, protein and albumin were lower. Three different IGF-I binding protein fractions were found with apparent molecular weights of >200, 140–160 and 45–65 kD. Relative amounts of IGF-I binding proteins were similar, although great differences in hormones and metabolites were found in cows, bulls and calves. Accessible binding sites were higher in dairy cows than in calves and bulls, mainly owing to the fact that dairy cows had lower concentrations of IGF-I bound to these fractions. Additionally, we found significant negative correlations between total accessible binding sites and total IGF-I concentrations. There were significant differences in the distribution of binding proteins. In particular, there was a shift of binding ability from the 140–160 to the 45–65 kD binding sites from the end of pregnancy to early lactation. Amounts of IGF-I bound to proteins increased from lactating to dry cows and calves and were highest in bulls. IGF-I levels in the >200 kD fraction was lower in lactating than in dry cows, and lower in cows than in calves and bulls. IGF-I measured in the 140–160 kD fraction was lowest in lactating cows and comparable in dry cows, calves and bulls. Concentrations of IGF-I in the 45–65 kD fraction were lowest in cows and highest in bulls. In conclusion, there were marked differences in growing, pregnant and lactating cattle, particularly as concerns accessible protein binding and amounts of IGF-I bound to proteins.
High frequency of cancer in cold thyroid nodules occurring at young age
Authors: Belfiore Antonino , Giuffrida Dario , La Rosa Giacomo L. , Ippolito Orazio , Russo Giovanna , Fiumara Antonio , Vigneri Riccardo , Filetti Sebastiano
Published: December 2008

In order to evaluate the risk of malignancy of cold thyroid nodules occurring in young as compared with adult patients, we studied a consecutive series of 2327 patients with a solitary cold thyroid nodule over a 6-year period. None of these patients had been previously irradiated in the neck or head. Fine needle aspiration of the nodule and cytologic examination were carried out in all patients and, on the basis of this evaluation and clinical examination 391 patients were selected for surgery; 109 patients were 4–20 years old and 2218 patients were older than 20 years. Malignancy was found in 11 (10.1%) and in 112 (5.0%) of cold thyroid nodules occurring in young and adult patients, respectively. The annual incidence of cold thyroid nodules in the population of the area studied was 5.2 vs 55.9 (per 105 inhabitants) in the young and in the adult group, respectively, and the annual incidence of thyroid cancer was 0.53 vs 2.82 (per 105 inhabitants) in the young and in the adult patients, respectively. The present study indicates, therefore, that in the absence of head or neck irradiation, cold thyroid nodules are much less frequent in young age, but that the malignancy rate of cold nodules occurring in young patients is 2-fold higher than in adults patients
Thyroid hormone and not growth hormone is the principle regulator of mammalian mitochondrial biogenesis
Authors: Mutvei A. , Husman B. , Andersson G. , Nelson B. D.
Published: December 2008

T3 and GH have been implicated in the regulation of mitochondrial biogenesis. Since thyroid hormone promotes the synthesis of growth hormone, its control of human mitochondrial biogenesis could arise through a permissive action on GH biosynthesis. This was studied in hypophysectomized rats treated with T3 and/or human GH by the continuous infusion of hormone for 6 days from mini-infusion pumps implanted sc. Increases in mitochondrial respiration, enzyme activites, and protein synthesis were found in isolated liver mitochondria from rats receiving T3. In contrast, GH alone had no effect, nor did it increase the response to T3. Since it has been argued that mitochondrial biogenesis results from a direct interaction (binding) of GH with mitochondria, GH-specific binding sites were measured with 125I-bGH, a specific somatogenic receptor ligand, in isolated mitochondrial membranes in vitro. In addition, the intracellular endocytic uptake of 125I-bGH injected in vivo was compared in purified subcellular membrane fractions and mitochondria. No evidence in favour of specific GH interaction on mitochondrial membranes was found by either test. It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.
Effects of vasoactive intestinal polypeptide, TRH, and dopamine on prolactin secretion in estrogen-primed postmenopausal women
Authors: Couzinet Béatrice , Dorey François , Schaison Gilbert
Published: December 2008

Prolactin secretion is influenced by at least three important hypothalamic neurotransmitters: TRH, vasoactive intestinal polypeptide and dopamine. The purpose of this study was to determine whether, in estradiol-primed postmenopausal women, the PRL response to TRH, vasoactive intestinal polypeptide, and dopamine differed. Ten postmenopausal women were studied during treatment with estradiol benzoate at a dose of 0.625 mg per day during 15 days. TRH (200 μg iv), saline infusion, vasoactive intestinal polypeptide (75 μg infused iv during 15 min), coadministration of vasoactive intestinal polypeptide and TRH, and dopamine (4 μg · kg−1 · min−1 iv for 3 h) were administered for 5 consecutive days before and during the last 5 days of estradiol benzoate treatment. Before estradiol benzoate administration, the PRL response to TRH was significantly greater than that of vasoactive intestinal polypeptide. Estradiol benzoate treatment increased significantly the PRL release induced by TRH (p < 0.01), but did not modify the response to vasoactive intestinal polypeptide. At the end of estradiol benzoate treatment, the maximal increase in PRL after the combined (vasoactive intestinal polypeptide + TRH) test was greater than that obtained with TRH alone and occurred earlier (p < 0.04). Dopamine suppressed PRL secretion to a similar extent after estradiol benzoate treatment. Thus: 1) in postmenopausal women, estrogens act as stimulators of PRL release; 2) estrogens are able to increase TRH-stimulated PRL secretion but not the response to vasoactive intestinal polypeptide and to reveal the additive effect of TRH and vasoactive intestinal polypeptide; 3) estradiol does not modify the effectiveness of dopamine as an inhibitor of PRL secretion; 4) these results suggest different intracellular mechanisms of the action of TRH, vasoactive intestinal polypeptide and dopamine on PRL secretion.
Heterogeneity of pituitary adenoma cell subpopulations from acromegalic patients obtained by Percoll density gradient centrifugation
Authors: Hofland Leo J. , van Koetsveld Peter M. , Verleun Theo M. , Lamberts Steven W. J.
Published: December 2008

Pituitary adenoma cells from 6 acromegalic patients were separated on continuous Percoll density gradients according to differences in their density. Two adenomas produced GH only in culture, the other 4 adenomas produced either GH and PRL (one adenoma) or GH and α-subunit (one adenoma) or GH, PRL and α-subunit (2 adenomas). The cell subpopulations obtained by this technique differed in the amount of hormone production per 105 cells: GH release decreased from the low density fractions to the higher density fractions in 5 of 6 adenomas. Intracellular GH levels completely followed this profile. In the mixed GH/α-subunit adenomas the α-subunit profile completely paralleled the GH profile, whereas in the mixed GH/PRL adenomas the PRL profile showed a pattern different from that of GH (and α-subunit). In neither of the adenomas did we find any differences between the subpopulations with respect to the responsiveness of GH, PRL or α-subunit release to GHRH, TRH and the somatostatin analogue SMS 201-995. Conclusions: 1. Within pituitary adenomas from acromegalic patients heterogeneity exists with respect to hormone production per cell. 2. The cell subpopulations obtained by density gradient centrifugation are not different in their responsiveness to SMS 201-995, GHRH or TRH. 3. Because GH and α-subunit release by the fractions from the mixed GH/α-subunit secreting adenomas were completely parallel, further evidence for co-release of GH and α-subunit by the same tumoural cells is provided.
Expression and function of protein kinase C isozymes
Authors: Huang Kuo-Ping , Huang Freesia L. , Nakabayashi Hiroki , Yoshida Yasuyoshi
Published: December 2008

Three protein kinase C (PKC) isozymes, type I, II, and III, have been identified as the major Ca2+/phospholipid-stimulated protein kinases in the various animal tissues. Based on the immunochemical analysis it was demonstrated that PKC I was encoded by γ cDNA, PKC II by the alternatively spliced βI and βII cDNAs, and PKC III by α cDNA. The expression of these enzymes appears to be tissue-specific and developmentally regulated. The central nervous system expresses high level of all three isozymes and the peripheral tissues mainly PKC II and III. During brain development, the expression of PKC I appears to follow the progress of synaptogenesis, whereas PKC II and III increase progressively from fetus up to 2–3 weeks of age. The level of PKC I in adult brain is highest in the cerebellum, hippocampus, amygdala, and cerebral cortex especially in those cortical regions being important for visual information processing and storage. The role of PKC II and III in cellular regulation was investigated by treatment of rat basophilic leukemia cells with the phorbol ester, phorbol 12-myristate 13-acetate. This phorbol ester caused a faster degradation of PKC II than III, indicating a differential down-regulation of these two enzymes by this compound. The results presented in this study support the contention that each species of PKC has a distinct function in the regulation of a variety of cellular processes.
Effects of protein kinase C activation on cyclic AMP and testosterone production of rat Leydig cells in vitro
Authors: Nikula Hannu , Huhtaniemi Ilpo
Published: December 2008

The role of protein kinase C in modulation of the endocrine function of rat Leydig cells was studied. Percoll-purified rat Leydig cells were stimulated with hCG, forskolin, cholera toxin, pertussis toxin and 8-bromo-cAMP in the presence and absence of two activators of protein kinase C, 12-0-tetradecanoylphorbol 13-acetate (TPA) or 1-oleoyl-2-acetyl-sn-glycerol (OAG). The two activators had no effect on basal cAMP, but decreased hCG-stimulated, and increased cholera toxinand forskolin-stimulated cAMP production. Cells pre-incubated with pertussis toxin showed enhanced rate of cAMP production in response to forskolin, but were no more responsive to TPA and OAG stimulation. These findings suggest that protein kinase C activation may on one hand inhibit the LH-receptor and Gs-protein coupling and on the other hand inhibit the Gi-protein mediated suppression of adenylyl cyclase activity. TPA and OAG effects on testosterone production were measured in the absence and presence of 8-bromo-cAMP stimulation. TPA enhanced basal testosterone production, but this effect was shifted to inhibition when steroidogenesis was stimulated by 8-bromo-cAMP. The OAG effect on testosterone production was inhibitory throughout the dose-response curve of 8-bromo-cAMP. The basal stimulation of testosterone production by TPA was probably due to a marginal increase of cAMP caused by inhibition of the Gi-protein, since a similar effect was observed by pertussis toxin, and therafter TPA was without effect on testosterone. The inhibition of stimulated testosterone production by TPA and OAG indicates that protein kinase C activity also affects steroidogenesis at a step(s) beyound cAMP formation.
Hypersensitivity to arginine of both B and D pancreatic cells in adult streptozotocin-diabetic rats
Authors: Zerbib A. , Ribes G. , Gross R. , Puech R. , Loubatières-Mariani M. M.
Published: December 2008

Insulin and pancreatic somatostatin secretions were studied after stimulation with an arginine infusion (5 mmol/1) in isolated perfused pancreata of adult streptozotocin-diabetic rats. In the presence of 2.8 mmol/l glucose, arginine clearly stimulated insulin and somatostatin secretions in diabetic rats, whereas it was ineffective in normal rats. Thus, not only the B-cells, but also the D-cells of the pancreas from streptozotocindiabetic rats are hypersensitive to arginine. The infusion of insulin (4 U/l) did not modify this hypersensitivity of the D-cells to arginine in pancreata of streptozotocindiabetic rats.
Modulation of calciumflux influences interleukin 1 β effects on insulin release from isolated islets of Langerhans
Authors: Helqvist Steffen , Bouchelouche Pierre , Andersen Henrik Ullits , Nerup Jørn
Published: December 2008

The controlled flux of calcium across the cell membrane is intimately linked to the release of insulin from pancreatic beta-cells, but the uncontrolled influx of calcium is a common final denominator of cell death. Because interleukin 1 has been shown to be cytotoxic to beta-cells in isolated rat islets of Langerhans and since interleukin 1 has a calcium ionophore effect on other cell types, this study was designed to test whether alterations of the calcium flux across the beta-cell membrane would influence the effects of interleukin 1 on isolated rat and mouse islets. Further, the cytosolic free Ca2+ concentration was measured by the fura-2 method in rat islets during acute interleukin 1 exposure. Treatment with 10 μmol/l of verapamil (a potent blocker of the voltage-dependent calcium channel) tended to suppress the inhibitory effect of interleukin 1 on insulin release from rat islets, suggesting protection against cytotoxicity. Conversely, a stimulatory effect of interleukin 1 on mouse islets during 6 days of exposure to interleukin 1 was turned into inhibition by high extracellular calcium concentration. Interleukin 1 did not have any acute effect on cytosolic free Ca2+ concentration. In conclusion, interleukin 1 has no specific calcium ionophore effect on beta-cells, but alterations of the calcium flux across the beta-cell membrane influence the functional effects of interleukin 1, suggesting interference with cell function and toxicity, which would likely be accompanied by an uncontrolled influx of calcium.
Inhibition of human thyroid peroxidase gene expression by interleukin 1
Authors: Ashizawa Kiyoto , Yamashita Shunichi , Tobinaga Tamami , Nagayama Yuji , Kimura Hironori , Hirayu Hideshi , Izumi Motomori , Nagataki Shigenobu
Published: December 2008

We have already demonstrated the inhibitory effect of interleukin 1 on thyroglobulin gene expression. Recent availability of thyroid peroxidase cDNA has allowed us to investigate the regulation of thyroid peroxidase gene. Therefore, the regulation of thyroid peroxidase mRNA by interleukin 1 in cultured human thyrocytes was investigated. Thyrocytes dispersed from thyroid tissues from patients with Graves' disease were incubated with TSH with or withtout recombinant human interleukin 1. Unstimulated human thyrocytes did not contain any detectable thyroid peroxidase mRNA, however, TSH-stimulated thyrocytes expressed four thyroid peroxidase mRNA transcripts (4.0, 3.2, 2.1 and 1.7 kb, respectively). Both interleukin 1 α and β inhibited TSH-induced thyroid peroxidase mRNA in a dose responsive manner; 103 U/l interleukin l caused maximal suppression of TSH-induced thyroid peroxidase mRNA level to nearly basal levels. Interleukin l also inhibited cAMP analogue 8-bromo-cyclic AMP induced thyroid peroxidase mRNA level. In contrast the γ-actin mRNA hybridization signal was not altered in control or treated cells. These results demonstrate that interleukin 1 directly inhibits TSH-induced thyroid peroxidase gene expression and provide further evidence for a paracrine role of interleukin 1 as a local inhibitor of thyroid hormone synthesis.
A highly sensitive sandwich enzyme immunoassay of urinary growth hormone in children with short stature, Turner's syndrome, and simple obesity
Authors: Tomita Hiroshi , Ogawa Masamichi , Kamijo Takashi , Mori Osamu , Ishikawa Eiji , Mohri Zen-ichi , Murakami Yoshiaki
Published: December 2008

GH values were determined by a highly sensitive sandwich enzyme immunoassay in the 1st morning and/or 24-h accumulated urine samples in 94 children (short stature 70, including 14 with complete GH deficiency, 9 with partial GH deficiency, and 47 with GH-normal short stature; Turner's syndrome, 10, and simple obesity, 14). GH values were also determined in the 2nd to 4th urine samples taken on the same day together with the 1st morning urine in 5 of them. GH values in the 1st morning urine correlated significantly with those of the 24-h urine and with serum peak and mean GH values during nocturnal sleep as a physiological GH secretion test. The 2nd to 4th urines had lower GH concentrations than the 1st morning urine. The GH value of the 1st morning urine in complete GH deficiency was significantly lower than those in GH-normal short stature, partial GH deficiency and Turner's syndrome. However, no significant difference was detected in urinary GH values between complete GH deficiency and simple obesity. We conclude that 1st morning urinary GH estimation may be useful for differentiation of complete GH deficiency from other causes of short stature, but may be difficult for the distinction between complete GH deficiency and obesity with normal GH secretory ability.
5α-Reductase activity regulates testosterone accumulation in two bands of immature cultured Leydig cells isolated on Percoll density gradients
Authors: Murono Eisuke P. , Washburn Amie L.
Published: December 2008

The 5α-reductase inhibitor, 4-methyl-4-aza-3-oxo-5α-pregnan-20(s)-carboxylate was utilitzed to examine maturational changes in testosterone synthesizing capacity of Leydig cells localizing in Band 2 and Band 3 of Percoll density gradients. Immature Band 2 Leydig cells (from 25- to 39-day-old rats) cultured without the 5α-reductase inhibitor, produced increased testosterone in response to hCG or 8-br-cAMP; however, basal, hCG- or 8-br-cAMP-stimulated testosterone accumulation was 4- to 12-fold higher when cells were cultured in the presence of inhibitor. Band 2 cells from older rats produced much less testosterone in response to hCG or 8-br-cAMP (<3.5 pmol/105), even when cultured with the inhibitor. Although immature Band 3 cells cultured in the absence of 5α-reductase inhibitor produced increased testosterone in response to hCG or 8-br-cAMP, testosterone levels were relatively low, because elevated 5α-reductase prevented appreciable androgen accumulation; however, Band 3 cells from older rats (over 39 days old) accumulated progressively more testosterone, because of the age-dependent decline in 5α-reductase activity. Immature Band 3 cells cultured with the 5α-reductase inhibitor accumulated 20- to 44-fold more testosterone in response to hCG of 8-br-cAMP. Thus, testosterone levels in control, hCG- or 8-br-cAMP-treated Band 3 cells form 39-day-old rats were 61.5, 177.2, and 500.3 pmol/105 cells, respectively. Testosterone declined from these high immature levels; however, testosterone still was relatively high in Band 3 cells of 63-day-old animals (83.4 and 98.3 pmol/105 cells in response to hCG or 8-br-cAMP, respectively). These studies demonstrate the viability of Leydig cells localizing in Band 2, emphasize the role of 5α-reductase activity in regulating testosterone accumulation of Leydig cells in both Band 2 and Band 3 and demonstrate differences in the pattern of testosterone production with maturation in cultured Leydig cells in Band 2 and Band 3.
Receptor-mediated endocytosis of insulin: inhibition of [125I]iodoinsulin internalization in insulin resistant diabetic states of man
Authors: Grunberger George , Geiger Dominique , Carpentier Jean-Louis , Robert Alec , Gorden Phillip
Published: December 2008

We have used electron microscopic autoradiography to quantitatively study receptor-mediated endocytosis of [125I] insulin in freshly isolated monocytes from patients with non-insulin-dependent diabetes mellitus. In obese, non-obese, and lipoatrophic patients with diabetes, internalization of [125I] insulin was impaired at 30 min of incubation at 37°C. By 60 min of incubation, however, internalization was indistinguishable from that of normals. In obese non-diabetic controls, internalization at 30 min was slightly less than internalization in normals but greater than that of the diabetic group. Dieting was associated with normalization of internalization in the obese group. We conclude that the rate of [125I]insulin insulin internalization is impaired in non-insulin-dependent diabetes and compare this to previously reported results in insulin-dependent diabetes mellitus.
The role of insulin-like growth factor I in growth of diabetic rats
Authors: Binz Katharina , Zapf Jürgen , Froesch E. Rudolf
Published: December 2008

Insulin-deficient, streptozotocin-diabetic rats show severe metabolic disturbances and stop growing. Besides insulin, these animals also lack growth hormone and insulin-like growth factor-I. We examined whether or not growth parameters correlate with IGF-I serum levels in young rats with streptozotocin-diabetes of different severity. In the diabetic rats, blood glucose varied between 18.4 and 38.6 mmol/1 (healthy controls between 6.1 and 9.3), IGF-I serum levels between 2.6 and 15.6 nmol/1 (controls between 19.6 and 26.5), and serum insulin levels between 0.05 and 0.14 nmol/1 (controls between 0.36 and 0.55). We found a highly significant linear correlation between IGF-I serum levels and the two investigated growth parameters, tibial epiphyseal width and longitudinal tibial bone growth. The finding that these indices of growth are strongly correlated with IGF-I serum levels in young rats with diabetes of different severity, suggests that IGF-I is a major determinant of growth. This is in keeping with our earlier demonstration that exogenously infused IGF-I promotes growth in diabetic rats.