bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract.
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

Abstract.
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

Abstract.
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

Abstract.
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

Abstract.
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

Abstract.
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

Abstract.
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

Abstract.
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.
Antibodies to 'second colloid antigen'. A study on the prevalence in sporadic forms of congenital hypothyroidism
Authors: van Trotsenburg Paul , Vulsma Thomas , Bloot André M. , Van der Gaag Reindert D. , Lens Jan Willem , Drexhage Hemmo A. , de Vijlder JanJ. 
Published: December 2008

Abstract.
Antibodies against the so called 'second colloid antigen' (CA2 antibodies) occurred in 51% of the mothers of hypothyroid children detected by screening for neonatal congenital hypothyroidism in Quebec (N = 49) and in The Netherlands (N = 26). In The Netherlands where corresponding neonatal serum was available, 31% (8 of 26) of the infants with congenital hypothyroidism were positive for antibodies against the second colloid antigen. When during follow-up, 3 to 5 years after diagnosis, the mothers and their children were investigated, 46% (7 of 15) of the mothers were positive for antibodies against the second colloid antigen, whereas 29% (4 of 14) of the hypothyroid children were also positive. Various control groups did not show more than a 12% positivity. This presence of thyroid-reactive antibodies in a proportion of the hypothyroid children 3 to 5 years after diagnosis is not compatible with a mere transplacental passage; it indicates that the antibodies must be produced by the mothers and by the children themselves. We conclude that a thyroid autoimmune response occurs in a considerable part of infants with congenital hypothyroidism and their mothers and that this immune response seems to persist in both of them for years.
Lys- and Tyr-arylamidase activities in serum and brain during the estrous cycle of the rat
Authors: de Gandarias J. M. , Casis L. , Irazusta J. , Echevarría E. , Arechaga G. , Ramírez M. 
Published: December 2008

Abstract.
Peptidase enzymes are involved in neuropeptide processing or degradation. In order to analyse a possible functional participation of these enzymes, arylamidase activity of several rat brain regions and serum was assayed in the soluble fraction during the estrous cycle using L-Lys- and L-Tyr-β-naphthylamide as substrates. Significant differences were present in the hypothalamus, the pituitary and serum when both substrates were used. However, there were no differences in cortical areas. These results suggest a role for arylamidase activity in the hormonal changes that happen during the estrous cycle of the rat.
Human interleukin 1β stimulates islet insulin release by a mechanism not dependent on changes in phospholipase C and protein kinase C activities or Ca2+ handling
Authors: Welsh Nils , Nilsson Thomas , Hallberg Anders , Arkhammar Per , Berggren Per-Olof , Sandler Stellan 
Published: December 2008

Abstract.
Isolated islets from adult rats or obese hyperglycemic (ob/ob) mice were incubated with human recombinant interleukin 1β in order to study whether the acute effects of the cytokine on islet insulin release are associated with changes in islet phospholipase C activity, Ca2+ handling or protein phosphorylation. The cytokine stimulated insulin release both at low and high glucose concentrations during one hour incubations. In shortterm incubations (<1 min) interleukin 1β did not affect the production of inositoltrisphosphate. Addition of interleukin 1β affected neither the cytoplasmic free Ca2+ concentration at rest nor that observed subsequent to stimulation with a high concentration of glucose. Furthermore, the endogenous protein kinase C activity, as visualized by immunoprecipitation of a 32P-labelled substrate for this enzyme, was not altered by interleukin 1β. Separation of 32P-labelled proteins by means of 2-dimensional gel electrophoresis failed to reveal any specific effects of the cytokine on the total protein phosphorylation activity. These results suggest that the stimulatory effects on insulin release exerted by interleukin 1β are not caused by acute activation of phospholipase C and protein kinase C or by an alteration of islet Ca2+ handling of the B-cells.
Pituitary-testicular axis in obese men during short-term fasting
Authors: Röjdmark Sven , Asplund Anette , Rössner Stephan 
Published: December 2008

Abstract.
To investigate whether short-term fasting affects the pituitary-testicular axis in obese subjects, 9 massively obese men (Body Mass Index 39.0 ± 1.3, mean± sem) were given two identical iv GnRH tests, the first (control) after an overnight fast, the second after 56 h of food deprivation. Short-term fasting augmented the GnRH-induced LH incremental area by 26%(1317±251 vs 1661 ± 297 U · 1−1 · min−1, p <0.05), but failed to affect the corresponding testosterone incremental area. Eight non-obese normal men (Body Mass Index 22.2 ± 0.5) were investigated for comparison. All of them were studied according to the same protocol as the obese group. Short-term fasting increased the GnRH-elicited LH response by 67% in the non-obese group (LH incremental areas 2147 ± 304 vs 3581 ± 256, p <0.01), and the corresponding testosterone response by 180% (testosterone incremental areas 111 ±61 vs 311±49 μg · 1−1 · min−1, p <0.01). These results imply that food deprivation affects the pituitary-testicular axis differently in obese and non-obese men.
Sequential immunohistochemical expression of IGF-I and the transferrin receptor in regenerating rat muscle in vivo
Authors: Jennische Eva 
Published: December 2008

Abstract.
The immunohistochemical expression of insulin-like growth factor I and the transferrin receptor was investigated in regenerating rat skeletal muscle. Muscle injury was induced in the extensor digitorum longus muscle in one hind limb by tourniquet ischemia. The regenerating muscles were investigated 3 to 7 days after the injury. Expression of IGF-I and the transferrin receptor was demonstrated in cryostat sections by a doublestaining method. It was found that both markers were transiently expressed by the regenerating muscle cells. Expression of IGF-I immunoreactivity preceded that of the transferrin receptor and the staining for IGF-I disappeared 1 to 2 days before the staining for the transferrin receptor. The data are compatible with a regulatory role of IGF-I on the transferrin receptor.
Changes of serum thyroid hormone levels induce malformations on early embryogenesis in rats
Authors: Harakawa Seijiro , Akazawa Shoichi , Akazawa Mihoko , Hashimoto Masumi , Yamashita Shunichi , Izumi Motomori , Nagataki Shigenobu 
Published: December 2008

Abstract.
The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternalfetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed in 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period.
Insulin-like growth factors I and II in healthy man.
Authors: Guler Hans-Peter , Zapf Jürgen , Schmid Christoph , Froesch E. Rudolf 
Published: December 2008

Abstract.
IGF-I and -II share specific serum carrier proteins which elute on neutral Sephadex G-200 gel permeation chromatography at apparent molecular masses of 50 and 200 kD. The half-lives of free and carrier protein-bound 125I-IGF-I and -II were determined after bolus injections of the tracers into two normal adults. Labelled IGF-I and -II migrated first with the 50-kD and later with the 200-kD complex. In these complexes their apparent half-lives were 20–30 min and 12–15 h, respectively. The apparent half-life of free 125I-IGF-I and -II was 10–12 min. In a second set of experiments, recombinant human insulin-like growth factor I was infused during 6 days in two healthy adults at a dose of 20 μg · kg−1 · h−1 (corresponding to around 30 mg/day). Serum obtained before and during the infusion was subjected to neutral Sephadex G-200 gel permeation chromatography and fractions were pooled according to the apparent molecular masses at which the carrier protein complexes elute. IGF-I and -II in these pools were determined by RIA. Before the IGF-I infusion, 92 and 272 μg/l of IGF-I and -II were found in the 200-kD complex, 45 and 91 μg/l in the 50-kD complex, and 15 and 5 μg/l were present in the free form. Corresponding figures during the IGF-I infusion were 389 and 18 μg/l for the 200-Kd complex, 201 and 54 μg/l for the 50-kD complex, and 80 and < 1 μg/l for free IGF-I and -II. Using the half-lives of the tracer studies and the levels of the different molecular weight forms of IGF in serum, the production rates for IGF-I and -II were calculated to be 10 mg and 13 mg per day.
Regulation of amino acid transport in rat and human thyroid cells
Authors: Rotella C. M. , Piani F. , Frediani U. , Toccafondi R. 
Published: December 2008

Abstract.
To clarify the role of insulin, IGF-I and TSH in thyroid cell regulation, their effects on amino acid transport were studied separately. These effects were noted and compared using both the Wistar rat thyroid cell line and human thyroid cell cultures. Insulin, IGF-I and TSH were able independently to induce the radiolabelled α-aminoisobutyric acid transport within the rat thyroid cells: TSH stimulated the amino acid transport in rat thyroid cells in a dose-dependent way from 1 pmol/l to 10 nmol/l. Similarly, insulin increased amino acid transport significantly from 0.17 nmol/1 up to 0.17 μmol/l and IGF-I from 0.13 pmol/l up to 0.13 μmol/l. The combined effects of insulin and TSH on amino acid transport were equal to the theoretical sum of the activities, whereas those of IGF-I and TSH were greater than the theoretical one. When human thyroid cell cultures were used, a significant increase of labelled amino acid transport was induced by TSH, i.e. from 0.1 pmol/l to 10 pmol/l; IGF-I stimulated amino acid transport in a range from 0.13 pmol/l to 13 pmol/l, under the same conditions. Conversely, only large doses of insulin, i.e. 1.7 nmol/l, were able weakly to stimulate amino acid transport. When submaximal TSH and IGF-I doses were co-incubated in human thyroid cells, an additive effect on amino acid transport was observed.