bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology, yield and functional integrity of islet-like cell clusters in tissue culture of human fetal pancreata obtained after different means of abortion
Authors: Otonkoski Timo , Knip Mikael , Panula Pertti , Andersson Sture , Wong Inés , Goldman Hy , Simell Olli
Published: December 2008

Abstract. Morphology, yield and function were studied in cultured islet-like cell clusters (ICC) from 140 human fetal pancreata obtained after abortions of different types performed at 11–23 weeks of gestation (12 by hysterotomy, 75 by mechanical dilation and extraction, and 53 induced with prostaglandin). After collagenase digestion and culture in medium supplemented with 10% human serum, up to 2000 free-floating ICC were formed from a single pancreas. Randomly scattered insulin- and glucagon-immunoreactive cells were found in the medullary part of the ICC. More than 100 ICC developed in 100% of the hysterotomies and 87% of the mechanical abortions, but in only 53% of the prostaglandin-induced abortions. Insulin and glucagon levels in the culture medium decreased rapidly during the first 7 days of culture, but then remained stable for at least 31 days. The hysterotomy-derived ICC responded to 10 mmol/l theophylline plus 20 mmol/l glucose by a 12.2 ± 3.1 (sem, N = 7) fold increase in insulin release, as compared with a 5.4 ± 0.9 fold response of the prostaglandin ICC (N = 16; P < 0.02). Despite the low proportion of B-cells, (pro)insulin biosynthesis accounted for 10% of the total protein biosynthesis in low (2 mmol/l) glucose. In conclusion, the yield and viability of the ICC were clearly better, if prostaglandin had not been used for the induction of the abortion.
Central effects of catecholamine antagonists on angiotensin-induced vasopressin secretion in conscious rats
Authors: Yamaguchi Ken'ichi , Karakida Takeo , Koike Mamoru , Hama Hitoshi
Published: December 2008

Abstract. To evaluate the roles for catecholamines in angiotensin II (ANG II)-induced vasopressin (AVP) release, we examined in conscious rats the effects of intraventricular (ivt) administrations of catecholamine antagonists on plasma AVP responses to ivt applications of its agonists and ANG II. Plasma AVP was determined by RIA using trunk blood collected after decapitation. Dopamine (0.15 μmol), phenylephrine (an alpha-adrenergic agonist, 0.15 μmol) or ANG II (48.2 pmol) augmented plasma AVP 90 sec after the injection, whereas after isoproterenol (a beta-adrenergic agonist, 0.15 μmol) plasma AVP was unaffected. The plasma AVP responses to both dopamine and ANG II were significantly (P < 0.01) inhibited by haloperidol (a dopamine blocker, 0.15 μmol) given 10 min before administration of these agents. Pre-administration of phenoxybenzamine (an alpha antagonist, 0.15 μmol) which was confirmed to abolish the effect of phenylephrine, or propranolol (a beta antagonist, 0.15 μmol) did not block the effect of ANG II. Administration of haloperidol, phenoxybenzamine or propranolol alone was without effect on plasma AVP level. On the basis of these results, we concluded that ANG II-induced AVP secretion may be mediated and/or modulated by dopamine.
Influence of ascorbic acid on in vivo amidation of alpha-melanocyte stimulating hormone in guinea pig pituitary
Authors: Fenger Mogens , Hilsted Linda
Published: December 2008

Abstract. The effect of ascorbic acid depletion on the amidation of alphamelanocyte stimulating hormone (αMSH) was studied in vivo in guinea pig pituitary. After four weeks, the concentration of ascorbic acid was 1.20 ± 0.11 μmol/g tissue (mean ± sd) in the pituitary and 0.34 ± 0.07 μmol/g tissue in the cerebral cortex from the depleted animals versus 7.58 ± 0.08 and 1.51 ± 0.32 μmol/g tissue, respectively, in the control animals. In the pituitaries from the animals depleted of ascorbate (N = 4), the relative amount of αMSH was reduced to approximately half the values obtained in the control group (from 66.5 ± 4.6% of total ACTH-related peptides to 31.1 ± 12.2% (P < 0.0025)). A concomitant increase (from 5.9 ±3.1% to 19.4 ± 4.3% (P < 0.004)) in ACTH (1–14) (the glycine-extended precursor of αMSH) immunoreactivity and a smaller increase in ACTH (1–39) immunoreactivity was observed in the depleted guinea pigs. Gel chromatography and reversed-phase high-performance luquid chromatography showed that the αMSH and ACTH (1–14) immunoreactivity was of low molecular weight and partly mono- or diacetylated. Depletion of ascorbic acid had no influence on the degree of acetylation of αMSH and ACTH (1–14). It is concluded that depletion of ascorbic acid reduces the in vivo amidation of ACTH (1–14) in the guinea pig pituitary.
Possible involvement of diacylglycerol-activated, Ca2+-dependent protein kinase in glucose memory of the rat pancreatic B-cell
Authors: Niki Ichiro , Tamagawa Tatsuo , Niki Hatsumi , Niki Atsushi , Koide Tadataka , Sakamoto Nobuo
Published: December 2008

Abstract. Exposure to high concentrations of glucose potentiates insulin release from the pancreatic B-cell stimulated by various secretagogues after an interval under basal condition. We studied the role of diacylglycerol-activated, Ca2+-dependent protein kinase (protein kinase C) in this priming effect of glucose in rat pancreatic islets, using 12-O-tetradecanoyl phorbol-13-acetate (TPA), 1 -(5- isoquinolinesulfonyl)-2- methylpiperazine (H-7),N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004) and forskolin. The priming effect of glucose was mimiced by 10 nmol/l of TPA, an activator of protein kinase C, but not by 5 μmol/l of forskolin, which increases cAMP via activating adenylate cyclase. When pancreatic islets were exposed to glucose (10 mmol/l) together with 50 μmol/l of H-7, an inhibitor of protein kinase C, the secretory response to glucose (10 mmol/l) after a 30-min interval was significantly reduced compared with that in the islets previously exposed to 10 mmol/l glucose alone. In contrast, this was not the case for HA-1004, its inhibitory activity against protein kinase C being less potent than H-7. These findings suggest that protein kinase C may play an important role in the priming effect of glucose on the pancreatic B-cell.
Dissociation of qualitative and quantitative effects of the suppression of testicular testosterone upon spermatogenesis
Authors: Huang H. F. S. , Boccabella A. V.
Published: December 2008

Abstract. The present study examined the quantitative and qualitative effects of suppressed testicular testosterone concentration upon spermatogenesis. Adult male rats were given sc implants of 0.5- to 5-cm long testosterone filled silastic capsules (TC) for 10 weeks. Testicular testosterone concentrations were suppressed to below 5% of the control level in rats receiving 1.5- to 5-cm TC implants. Spermatogenesis was arrested at early spermatids in rats given 1.5-cm TC implants, but was maintained in those given 3- or 5-cm TC implants. The number of Al spermatogonia was 10–15% higher in rats bearing 0.75- to 1.5-cm TC implants, while a 5–15% reduction in preleptotene spermatocytes was noted in rats receiving 1.5-cm or longer TC implants. Linear regression analysis revealed a significant negative correlation between the number of A1 spermatogonia and the percent yield of preleptotene spermatocytes. This result illustrates the presence of a negative feedback mechanism in the regulation of A 1 spermatogonia. The lack of a correlation between the quantitative changes in germ cell number and the hormonal states suggests that factors or local mechanisms independent of the concentration of hormones are involved in the regulation of germ cell differentiation.
Blood levels, clearance rates and effects of epinephrine and norepinephrine on insulin and metabolites during α- and β-adrenergic blockade in cattle in vivo, and in vitro degradation of dopamine in bovine blood
Authors: Fröhli D. , Blum J. W.
Published: December 2008

Abstract. To study possible modifications of norepinephrine and epinephrine kinetics (metabolic clearance rate and half-times) by inhibition of binding to α-and/or β-adrenergic receptors, norepinephrine and epinephrine were iv infused in the absence or presence of the α-adrenergic blocking agent phentolamine, the β-adrenergic blocking agent propranolol, and during the combined administration of phentolamine and propranolol. In addition, recovery experiments were performed to investigate the in vitro degradation of dopamine, norepinephrine and epinephrine. Blood levels and kinetics of epinephrine were not modified by α-and β-adrenergic blockade, whereas norepinephrine clearance was reduced by α-adrenergic blockade, and was greater than epinephrine clearance. α- and β-adrenergic blockade markedly modified insulin, glucose and non-esterified fatty acid responses to epinephrine and norepinephrine. Norepinephrine and epinephrine could fully be recovered when added to bovine blood plasma. In contrast, dopamine obviously was immediately destructed by bovine, but not by human blood plasma, and should therefore barely be detectable in blood of cattle in vivo.
The bovine placenta: a specific radioreceptor assay for both insulin-like growth factor I and insulin-like growth factor II
Authors: van Buul-Offers Sylvia , Hoogerbrugge C. M. , de Poorter T. L.
Published: December 2008

Abstract. Binding of labelled IGF-I and IGF-II was studied to bovine, ovine and human placental cell membranes. The data show a preponderance of type I receptors in human placental membranes, and of type II receptors in ovine placental membranes, confirming reported data. In contrast, bovine placental membranes are rich in both type I and type II receptors. Therefore, the bovine placenta offers a good model for measuring specifically IGF-I (cross-reactivity with IGF-II 7%) and IGF-II (cross-reactivity with IGF-I 4%). By Scatchard analysis the apparent Kd (1–1.36 nmol/l) for the high affinity binding sites of the type I receptor is similar in all three preparations. Total binding capacity in ovine placental membranes is, however, 4 times lower. The affinity for the type II receptor is lower than for type I, whereas total binding capacity is higher. Affinity cross-linking confirms the competition experiments, showing binding of IGF-I to typical type I and of IGF-II to type II receptors.
Physiological and supraphysiological supplements of triiodothyronine do not influence the primary in vitro antibody response to trinitrophenylated Brucella abortus by spleen cells in serum-containing media
Authors: Filteau S.M. , Woodward Bill
Published: December 2008

Abstract. T3 supplements enhance splenic primary thymus-independent antibody responses in the mouse in vivo. The purpose of the present investigation was to determine whether this effect may be mediated, in part, by direct influences on the lymphocytes and/or accessory cells involved in the response. A range of T3 levels (3 × 10−10 to 10−5 mol/l) was tested in microcultures of separated spleen cells from CBA/J mice 33 days of age. The immune reaction examined in vitro was the primary antibody response to trinitrophenylated Brucella abortus (TNP-BA). T3 was without influence, throughout the concentration range tested, on the number of anti-TNP plasma cells generated per culture. This result was obtained using splenocytes either from well-nourished or from malnourished mice, and using both optimal and suboptimal numbers of TNP-BA. On the basis of the present results and a reinterpretation of previous published work, it is concluded that the influence of T3 supplements on splenic antibody responses in vivo is mediated indirectly. Direct influences of T3 on the T-independent antibody response, if such occur, must be maximized by subphysiological levels of the hormone.
Neuroendocrine effects of chronic administration of sodium valproate in epileptic patients
Authors: Invitti C. , Danesi L. , Dubini A. , Cavagnini F.
Published: December 2008

Abstract. In 10 untreated epileptic patients, we evaluated the functional integrity of the hypothalamic-pituitary axis before and during chronic treatment with sodium valproate, a gamma-aminobutyric acid-mimetic compound. The GH response to L-dopa (250–500 mg po) was absent in 3 and severely impaired in 2 of the 10 patients though being, on the average, only slightly lower in the epileptic subjects than in normal controls. Conversely, the GH rise following GHRH (0.5 μg/kg body weight, iv) was normal in 9 of the patients. A significant blunting of the GH response to L-dopa occurred in the 7 patients initially responsive after 6 month of sodium valproate (P < 0.05). The GH response to GHRH also underwent an evident though not significant attenuation. The ACTH and the ACTH/cortisol elevations elicited by metyrapone (35 mg/kg body weight infused over 4 h), and by CRH (1 μg/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P <0.05, <0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH (200 μg iv) remained normal over the whole study period. Growth arrest ensued in 1 patient after 6 months of sodium valproate and disappeared after drug withdrawl. These observations point to a defective hypothalamic control of GH secretion in some epileptic patients. They also indicate that chronic administration of sodium valproate, hence activation of central gamma-aminobutyric acid system, results in a blunting of the stimulated GH and ACTH secretion. Occasionally, a reversible arrest of skeletal growth may also ensue.
Effects of the antiprogestin RU486 on progesterone-dependent uterine development and bioassay of progestational activity in estrogen-primed immature female dogs
Authors: Concannon P. W. , Dillingham L. , Spitz I. M.
Published: December 2008

Abstract. A bioassay for progesterone activity in dogs was established based on uterine weight (mg/kg body weight) in immature beagles administered progesterone for 10 days starting 9 days after priming with estradiol cypionate (50 μg/kg, im). Progesterone doses of 0, 0.17, 0.5, 1.5, 13.5 and 40.5 mg/kg per day, im, produced dose-dependent increases in the weights of uterine horns obtained after 5 or 10 days of treatment. The total uterine responses (horn removed at 5 days plus horn and fundus removed at 10 days) to those were (mean ± sem) 374 ± 33, 465 ± 97, 684 ± 68, 795 ± 96, 1005 ± 38, 1232 ± 15 mg/kg, respectively. Responses to the 13.5 mg/kg per day dose of progesterone in dogs given the steroid antagonist RU486 at daily oral doses of 5, 20 and 50 mg/kg were reduced to values of 634 ± 24, 464 ± 74 and 468 ± 18 mg/kg, respectively, vs 1005 ± 38 mg/kg in controls. Mean progesterone levels were 27 ± 1 μg/l. The RU486 did not produce any consistent alterations in serum cortisol levels. The results suggest that, in immature bitches, uterine weight changes can be used to bioassay progestin activity following estrogen priming, RU486 is more potent as an antiprogestin than as an antiglucocorticoid, and RU486 at oral doses of 5 and 20 mg/kg exerts submaximal and maximal antiprogestin activity, respectively, in the presence of physiological levels of progesterone.
Growth factors and the thyroid: effects of treatment for hyper- and hypothyroidism on serum IGF-I and urinary epidermal growth factor concentrations
Authors: Westermark K. , Alm J. , Skottner A. , Karlsson A.
Published: December 2008

Abstract. We investigated the impact of thyroid hormone levels on serum concentrations of IGF-I and urinary epidermal growth factor (EGF) in hyper- and hypothyroid patients before and during medical treatment. Serum IGF-I levels measured with radioreceptorassay decreased in 12 hyperthyroid patients from 1.25 (1.02–1.80) to 1.02 (0.77–1.78) × 103 U/I (P < 0.01), whereas a non-significant increase in 8 hypothyroid patients – from 1.14 (0.85–1.40) to 1.39 (1.08–1.80) × 103 U/l was recorded. Urinary EGF, measured with radioimmunoassay decreased in 10 hyperthyroid patients from 68.0 (38.0–122.9) to 40.9 (23.6–100.3) μg/g creatinine (P <0.001) and increased in 7 hypothyroid subjects from 23.8 (17.5–35.8) to 36.1 (24.7–60.1) μg/g creatinine (P <0.05). In hyperthyroidism, but not in hypothyroidism, the urinary excretion of creatinine changed significantly from 0.66 (0.26–1.21) to 1.52 (0.81–2.59) g/l (P < 0.001) during treatment, thus affecting the EGF excretion values. However, a comparison of untreated hyperthyroid with untreated hypothyroid patients showed a highly significant difference in EGF excretion (P <0.001) despite a non-significant difference in creatinine excretion between the two groups. FT4 I concentrations correlated significantly (r = 0.83) (P <0.001) to EGF values in untreated hyperand hypo-thyroid patients. Data from the present study thus conform with the view that the growth promoting effect of thyroid hormones involves a stimulated synthesis or release of classic growth factors.
Thyroid function of subjects with goitre and cretinism in an endemic goitre area of rural China after use of iodized salt
Authors: Pang Xuan-Ping , Ouyang An , Su Tian-Sue , Hershman Jerome M.
Published: December 2008

Abstract. Endemic goitre and cretinism are still a public health problem in China. An epidemiological survey showed that about 5% of the inhabitants in Daxin village, Henan province, had goitre or cretinism after an iodized salt prevention programme had been carried out for two decades. The main food for the inhabitants of this area has an iodine content <30 nmol/kg and the water for cooking and drinking has an iodine concentration between 7–12 nmol/l. We studied thyroid function in subjects of this village. There were 42 with grade 0 goitre (males 29, females 13), 42 grade I (males 23, females 19), 27 grade II (males 9, females 18), 31 grade III (males 14, females 17) and 34 cretinism patients (males 30, females 4) diagnosed and classified according to WHO criteria. Serum T4, free T4, T3, free T3, T3 uptake, TSH and thyroglobulin were measured in these subjects. The patients with goitre or cretinism had significantly decreased serum free T4 and increased serum T3 and free T3 levels compared with those of controls. Thyroid size was positively correlated with age and serum thyroglobulin concentrations. Serum thyroglobulin was significantly increased even in the grade 0 goitre subjects. The percentages of subjects with serum free T4 < 12 nmol/l, T3 >2.5 nmol/l, free T3 >5.2 pmol/l, TSH >3.5 mU/l, T3/T4 ratio >0.03 and free T3/free T4 ratio >0.36 were significantly higher among goitre and cretinism patients than among controls. The data suggest that there is partial compensation for a marginal deficiency of iodine in the inhabitants of this village.
Effects of a selenium deficient diet on thyroid function of normal and perchlorate treated rats
Authors: Golstein J. , Corvilain B. , Lamy F. , Paquer D. , Dumont J. E.
Published: December 2008

Abstract. Pregnant rats were submitted to a selenium-deficient diet immediately after mating; it was continued for 4 weeks after delivery. The pups were sacrificed at 3 and 4 weeks of age. Perchlorate, an antithyroid agent inhibiting iodide trapping in the thyroid, was administered via the drinking water to half of the rats. Rats submitted to a normal laboratory diet and to the experimental diet supplemented with selenium were used as controls. The effects of selenium deficiency were an increase in the number of growth abnormalities, growth retardation, and decreased seleno-dependent glutathione peroxidase (GSH-Px) activity in plasma and in various organs. These effects were relieved by selenium supplementation in the diet. Perchlorate treatment induced the classic picture of primary hypothyroidism. Selenium deficiency increased thyroid hormone levels in perchlorate-treated rats and in controls drinking tap water. In the latter group, it also decreased TSH plasma concentration and thyroid weight. These effects were partially reversed by Se supplementation. In vitro experiments, performed on adult rats, revealed increased radioiodide uptake and organification in glands from the rats submitted to the selenium-free diet. Plasma T3 half-life was similar in control and Se-deficient rats. These data suggest a higher efficiency of thyroid hormone synthesis in the thyroids of selenium-deficient rats, despite a lower thyroid stimulation as evaluated by serum TSH. They are compatible with the hypothesis that decreased selenium supply, leading to a decreased GSH-Px in the thyroid, increases hydrogen peroxide steady state level and thus thyroid peroxidase activity and thyroid hormone synthesis.
Mammosomatotropes in human pituitary adenomas as revealed by electron microscopic double gold immunostaining method
Authors: Beckers A. , Courtoy R. , Stevenaert A. , Boniver J. , Closset J. , Frankenne F. , Reznik M. , Hennen G.
Published: December 2008

Abstract. Hormone production was studied in situ by immunocytochemical methods in 20 pituitary adenomas. Special attention was given to 13 adenomas removed from acromegalic patients. Out of them, 6 had mild to moderate hyperprolactinemia. Immunohistochemistry revealed PRL-containing cells without any close relationship with high PRL serum level in 6 patients. Double immunogold staining revealed mammosomatotrope cells characterized by simultaneous presence of GH and PRL in the same granules in 2 patients. Since mammosomatotropes have never been demonstrated in the normal pituitary, our results probably signify gene dysregulation in pituitary cells of those acromegalic patients.
Cortisol secretion in patients with normoprolactinemic amenorrhea
Authors: Boesgaard Søren , Hagen Claus , Andersen Anders Nyboe , Djursing Henning , Fenger Mogens
Published: December 2008

Abstract. Patients with functional amenorrhea have raised central dopaminergic activity and opioid-mediated GnRH inhibition leading to inhibition of hypothalamic-pituitary-ovarian function. In the present study, basal serum cortisol and ACTH levels were measured in normoprolactinemic amenorrheic patients with (N = 14) and without (N = 7) insulin-dependent diabetes mellitus. Basal serum cortisol levels was significantly (P < 0.01) elevated in patients with normoprolactinemic amenorrhea compared with normal women. Basal serum cortisol was significantly (P < 0.02) elevated in amenorheic diabetic patients compared with menstruating diabetic women. In the amenorrheic groups both cortisol and ACTH levels increased significantly (P <0.01) after dopamine D-2 receptor blockade, whereas no hormonal changes occurred in the control groups. It is concluded that patients with normoprolactinemic amenorrhea have elevated basal serum cortisol, the reason probably being hypersecretion of corticotropin-releasing hormone. Secondly that dopaminergic blockade with metoclopramide stimulates ACTH and cortisol secretion in patients presumed to have raised dopaminergic activity.
Thyroid cancer in Iceland 1955-1984
Authors: Hrafnkelsson J. , Jonasson J. G. , Sigurdsson G. , Sigvaldason H. , Tulinius H.
Published: December 2008

Abstract. A retrospective study was carried out on the incidence of thyroid cancer in Iceland from 1955 to 1984. During this 30-year period 406 cases of thyroid cancer were registered. The incidence of 9.5 for females and 3.4 for males per 100 000 per year is at least twice as high as in the other Nordic countries and among the highest incidence figures reported anywhere. A considerable increase in the reported incidence of thyroid cancer was noted around 1965. The mean size of the cancer nodules at diagnosis decreased at the same time and survival rates of patients improved. The incidence decreased again during the last 5 years of the study period. Mortality rates remained similar during this 30-year period. The survival rate corrected for intercurrent death was similar for both papillary and follicular carcinomas. All patients with anaplastic carcinomas died within one year of diagnosis. Cox's regression analysis with multiple covariates revealed that age at diagnosis, anaplastic and medullary history type as compared with papillary type, pathological evaluation of tumour extent, and calendar period of diagnosis had significant prognostic power. Sex and follicular vs papillary histology type were not significant prognostic factors.
Antibody-dependent cell-mediated growth inhibition of rat thyroid cells, FRTL-5, in patients with autoimmune thyroid diseases
Authors: Iida Yasuhiro , Kasagi Kanji , Tokuda Yasutaka , Arai Keisuke , Misaki Takashi , Konishi Junji
Published: December 2008

Abstract. We studied antibody-dependent mononuclear cell-mediated growth inhibition of thyroid cells in 18 untreated patients with Graves' disease, 18 patients with chronic thyroiditis, and 15 normal subjects by measuring the ability of their sera to inhibit [3H]thymidine incorporation into DNA in a rat thyroid cell line, FRTL-5, in the presence of normal mononuclear cells. [3H]thymidine incorporation was significantly inhibited in the presence of sera from patients with Graves' disease and chronic thyroiditis (P <0.001), whereas it was not affected in normal subjects. A significant correlation was observed between the inhibition of [3H]thymidine incorporation and the titre of anti-microsomal antibodies (P <0.05). The inhibitory effect on [3H]thymidine incorporation was significantly abolished when serum pre-absorbed with human thyroid membranes was used (P <0.005). These inhibitory effects on [3H]thymidine incorporation significantly correlated with those obtained by using IgG fractions (P <0.01). These data indicate that antibody-dependent mononuclear cell-mediated growth inhibtion may play a role in thyroid cell growth regulation in patients with autoimune thyroid disease.
Testosterone and the control of hypothalamic GnRH
Authors: Messi E. , Zanisi M. , Celotti F. , Motta M.
Published: December 2008

Abstract. The aim of the present study was to test the hypothesis that the restoring effect of testosterone on hypothalamic GnRH stores in orchidectomzied rats might be linked to the intrahypothalamic transformation of the hormone into estrogenic metabolites. To this purpose, advantage has been taken of the availability of the potent antiestrogen, tamoxifen (TMX). Different groups of adult male rats castrated since 4 weeks were submitted to a 6-day treatment with testosterone propionate (TP, 2 mg/rat daily); TMX (50 or 200 μg/rat daily); or TP (2 mg/rat daily) plus TMX (50 or 200 μg/rat daily). The animals were sacrificed 24 h after the last injection, and hypothalamic GnRH content was measured by radioimmunoassay. The results have confirmed the ability of TP to counteract the decreasing effect of orchidectomy on hypothalamic GnRH stores, and have shown that TMX does not have any intrinsic activity on this parameter. Furthermore, TMX at either dose used in the present experiments, was found not to be able to abolish the restoring effect of TP on MBH-GnRH stores. It is concluded that the action of testosterone on hypothalamic GnRH does not require the conversion of the hormone into estrogens.
Volume-regulated arginine vasopressin release in conscious dogs. Evidence for dopaminergic or opioid modulation?
Authors: Hellebrekers L.J. , Lagerweij E. , de Vries H W. , van Wimersma Greidanus Tj. B.
Published: December 2008

Abstract. The possibility of a dopaminergic and/or opioid modulation of the volume-regulated release of AVP was investigated in conscious dogs. Either bromocriptine, 10 μg/kg body weight po, or naloxone, 0.1 mg/kg body weight iv, was administered prior to induction of nonhypotensive hypovolemia. Volume contraction of 15 ml/kg body weight was induced gradually, over a period of 30 min. Basal plasma AVP levels in the bromocriptine group were not significantly different from control group values. Bromocriptine administration significantly augmented AVP release following volume contraction. Mean arterial pressure in the bromocriptine group decreased to a slightly, but significantly, lower level than that in the control group. Mean arterial pressures, however, did not adequately explain the magnitude of the AVP response in the bromocriptine group. In the naloxone group, neither baseline levels, nor AVP values following volume contraction, differed significantly from respective control group values. In conclusion, the results suggest the possibility of a stimulatory role for endogenous dopamine in the volume-regulated, but not the basal, release of AVP in conscious dogs.
Urinary iodine excretion in a geographically stratified Danish population sample not affected by iodination programmes.
Authors: Haas Vagn , Marley Margaret , Green Anders , Date John , Blichert-Toft Mogens , Mogensen Erik F.
Published: December 2008

Abstract. The excretion of urinary iodine was studied in a representative population sample from the county of Funen, Denmark, comprising 505 persons between 25–44 years of age, stratified according to geography, age, and sex. Urine samples were collected for 5 h during late afternoon and early evening. The 24-h iodine excretion was estimated on the basis of iodine and creatinine determinations using correlation equations determined in a pilot study of 50 men and women. The iodine excretion was significantly higher in men: 89 μg/24 h (median) than in women: 76 μg/24 h; the whole population: 85 μg/24 h. No significant differences were observed among the age groups studied. The iodine excretion was significantly higher in people living on small islands: 98 μg/24 h (median) compared with 84 μg/24 h in urban regions and 78 μg/24 h in rural districts. Median iodine excretion per gram of creatinine was 58.8 μg for the whole sample. The iodine excretion for men was 77% higher than reported in an earlier investigation performed in Funen, 1969, but still lower than internationally recommended (WHO).
3,3′,5′-Triiodothyronine inhibits ontogenetic development of iodothyronine-5′-deiodinase in the liver of the neonatal mouse
Authors: Han Doo Chol , Sato Kanji , Fujii Yuko , Ozawa Minoru , Imamura Hidehito , Tsushima Toshio , Shizume Kazuo
Published: December 2008

Abstract. To elucidate the effect of rT3 on iodothyronine-5′-deiodinating activity (I-5′-DA) in the liver of neonatal mice, rT3 was injected sc on the 5–8th day after birth and I-5′-DA in the liver was determined. A single injection of rT3 (0.01–1 μg/g) inhibited the ontogenetically developing I-5′-DA in a dose- and time-dependent manner. The inhibitory effect was reversible and specific for I-5′-DA. Lineweaver-Burk analysis revealed that the time- and dose-dependent decrease in the enzyme activity was due to a decrease in Vmax with no alteration in Km values (5 × 10−8 mol/l). The maximal inhibitory effect was observed at a dose of 1 μg rT3/g, whereas the inhibitory effect was diminished at greater doses (4–10 μg/g), probably owing to a contamination with T4 of the rT3 preparation administered. Furthermore, consistent with our previous in vitro findings, rT3 inhibited the I-5′-DA induced by T3 in the liver of neonatal mice. These findings suggest that rT3 inhibited I-5′-DA in the liver of neonatal mice by decreasing the amount of enzyme available to the substrate and that rT3 also elicited an antagonistic effect against T3 in the induction of I-5′-DA in vivo.
Prolactin stimulates creatine kinase activity and DNA synthesis in explants of human amnion
Authors: Golander A. , Weisman Y. , Spirer Z. , Binderman I. , Kaye A. M. , Sömjen D.
Published: December 2008

Abstract. To characterize the action of hPRL and human placental lactogen on the amnion, decidua and placenta, we examined the effects of these hormones on the brain type isozyme of creatine kinase in cultured explants of these tissues from normal deliveries. In the amnion, hPRL (1 mg/l) caused a 1.8-fold increase in creatine kinase specific activity in 24 h, whereas hGH (1 mg/l) or human placental lactogen (1 mg/l) had no effect; oPRL (1 mg/l) also caused a 2.5-fold increase in creatine kinase activity. Neither hPRL, human placental lactogen nor hGH had a significant effect on creatine kinase activity in the placenta or decidua. [3H]thymidine incorporation into DNA increased in parallel to the stimulation of creatine kinase activity. The predominant isozyme of creatine kinase in both the unstimulated and stimulated explants was the brain type isozyme. Creatine kinase activity in the amniotic tissue increased significantly 2 h after hPRL treatment and reached its highest value at 4 h. The enzyme activity in the amnion rose with increasing hPRL dose and showed a significant increase at physiologic concentrations as low as 0.01 mg/l. This study, therefore, provides evidence for biological action of prolactin in amniotic tissue, suggesting that the amnion is physiologically responsive to prolactin.
Immunohistochemical localization of atrial natriuretic peptide binding sites in juxtaglomerular cells and vascular walls of rat kidney
Authors: Naruse Mitsuhide , Nitta Kohsaku , Sanaka Tsutomu , Naruse Kiyoko , Demura Hiroshi , Inagami Tadashi , Shizume Kazuo , Sugino Nobuhiro
Published: December 2008

Abstract. Since the kidney is one of the major sites of action for atrial natriuretic peptide (ANP) and immunoreactive ANP has been detected in tissue extract by radioimmunoassay, we have applied the immunohistochemical technique by using the avidin-biotin complex method to investigate ANP binding sites in the rat kidney. Although no immunostaining was observed in the kidney of control rats, immunoreactive ANP was present in the juxtaglomerular cells, the vascular walls of interlobular arteries, arcuate arteries, arterioles including vas afferens and vas efferens, and the medullary peritubular capillary of ANP-pretreated rats. In contrast, no tubular structure was stained. These results suggest that ANP may affect renin secretion via its direct action on the juxtaglomerular cells and that it predominantly induces natriuresis by its effects on renal hemodynamics.
The circadian rhythm of melatonin in hypothyroidism and hyperthyroidism
Authors: Soszyński Piotr , Zgliczyński Stefan , Pucilowska Jolanta
Published: December 2008

Abstract. In order to determine the influence of thyroid function on the pineal gland in humans, the circadian rhythm of the serum melatonin concentration was estimated in 16 women with thyroid disorders: 8 with hypothyroidism and 8 with hyperthyroidism, as well as in 5 healthy controls. A significant melatonin circadian rhythm was observed in all the three groups studied. The melatonin rhythm parameters derived from cosinor analysis: mesor (controls: 0.163 ± 0.03 nmol/l (± sem), hypothyroid patients: 0.176 ± 0.22 nmol/l, and hyperthyroid patients: 0.167 ± 0.04 nmol), amplitude (0.155, 0.145 and 0.138 nmol/l, respectively), acrophase (1:38, 2:22 and 1:51 h, respectively) did not differ significantly in the three groups studied. Integrated 24-h melatonin secretion was also similar in patients and controls. The melatonin concentrations were positively correlated with TSH levels in hypothyroidism, and negatively correlated with T3 in hyperthyroidism. In conclusion: in patients with hypo- and hyperthyroidism the circadian rhythm of melatonin secretion is not altered.
Prolonged influence of a neonatal cyproterone acetate treatment on renal androgen binding in mice
Authors: Veyssiére G. , Gallon Ch. , Berger M. , Jean-Faucher Ch. , de Turckheim M. , Jean Cl.
Published: December 2008

Abstract. To determine whether neonatal endogenous androgens influence adult renal androgen binding, newborn male mice were injected from 1 to 10 days of age with cyproterone acetate and newborn females with testosterone from 1 to 10 days and from 20 to 40 days of age. In controls, at adulthood, the total cellular androgen receptor content was significantly higher in males (1700 200 receptors per cell) than in females (1060 ± 50) and, as expected, the nuclear receptor content was 12-fold higher in males. While the total number of receptors (1650 ± 220 per cell) was unchanged in adult males neonatally treated with cyproterone acetate, their distribution between cytosol and nucleus was similar to that in control females despite normal circulating and renal testosterone levels. The nuclear receptors represented 50, 7 and 11% of the total receptors in control males, control females and cyproterone acetate-treated males, respectively. The very low levels of nuclear receptors present in the kidney of cyproterone acetate-treated males probably explain the decreased sensitivity of this organ to testosterone. The nuclear receptor accumulation measured in adult animals after a single injection of testosterone did not seem to be affected by neonatal hormonal manipulations.
The bimodal effect of interleukin 1 on rat pancreatic beta-cells – stimulation followed by inhibition – depends upon dose, duration of exposure, and ambient glucose concentration
Authors: Spinas Giatgen A. , Palmer Jerry P. , Mandrup-Poulsen Thomas , Andersen Henrik , Nielsen Jens Høiriis , Nerup Jørn
Published: December 2008

Abstract. To investigate the hypothesis that interleukin 1 initially stimulates and then suppresses beta-cell function and that this sequential effect is directly related to interleukin 1 dose, duration of exposure, and ambient glucose concentration, insulin release was measured from cultured newborn rat islets exposed for 6 h to 6 days to interleukin 1 at doses ranging from 20 to 2000 ng/l at glucose concentrations of 3.3, 5.5 and 11 mmol/l. After 6 h of exposure and at all three glucose levels, all doses of interleukin 1 stimulated insulin release, maximal stimulation (370% of control) being observed at 5.5 mmol/l glucose and 100 ng/l interleukin 1. In contrast, after 6 days, all doses of interleukin 1 were inhibitory irrespective of glucose level, maximal inhibition (90%) being observed at 11 mmol/l glucose and 2000 ng/l interleukin 1. At 24 and 48 h of exposure, the biphasic effect of interleukin 1 was observed: lower doses of interleukin 1 at lower glucose concentrations at 24 h being more stimulatory with transition to inhibition directly related to higher glucose levels, higher interleukin 1 doses, and longer exposure. After 48 h, 200 ng/l of interleukin 1 increased insulin release to 220% at 3.3 mmol/l glucose, but at 11 mmol/l glucose a 60% suppression was seen. On the basis of these data we suggest that interleukin l's effect on beta-cells is bimodal: stimulation followed by inhibition. Increasing interleukin 1 dose and ambient glucose concentration shift this response to the left. Experimental results will, and in vivo effects may, depend upon these three variables.
Bioactivity and immunoactivity of growth hormone during dynamic testing of patients with acromegaly
Authors: Baldwin A. L. , Aston R. , Butler J. , Buchanan C. , Norman M.
Published: December 2008

Abstract. We have used the Nb2 cell proliferation bioassay for lactogenic hormones to investigate the biological activity of hGH in sera of patients with acromegaly. The specificity of the assay has been improved by the use of monoclonal antibodies to block the activity of individual lactogenic hormones. Disease activity in patients was assessed by scoring signs and symptoms, and by measuring IGF-I concentrations in some patients. Patients with a wide spectrum of disease activity were studied using a TRH test. hGH concentrations were measured by bioassay, RIA and immuno-radiometric assay (IRMA) at 0, 20 and 60 min after injection of TRH. There was a high degree of correlation between log10 of all hGH concentrations measured by bioassay and RIA (r = 0.995, P < 0.0001), between bioassay and IRMA (r = 0.990, P < 0.0001), and between RIA and IRMA (r = 0.995, P < 0.0001). In contrast to previous reports, we found no evidence for changes in the bioactivity of hGH secreted after pituitary stimulation.
Effects of heparin treatments in vivo and in vitro on adrenal angiotensin II receptors and angiotensin II-induced aldosterone production in rats
Authors: Azukizawa Sadahide , Iwasaki Ikuyo , Kigoshi Toshikazu , Uchida Kenzo , Morimoto Shinpei
Published: December 2008

Abstract. To evaluate the heparin effects in vivo and in vitro on adrenal angiotensin II receptors and angiotensin II-induced aldosterone production, we examined the angiotensin II binding and the maximum angiotensin II-induced aldosterone production using adrenal glomerulosa cells from rats treated with a heparin preparation containing benzyl alcohol (1500 IU/kg, twice daily for 6 weeks) or cells to which heparin (300 IU/l) was directly added. Comparison was made using the cells from rats treated with vehicle or the cells to which vehicle was directly added. Specific binding of [125I]iodo-angiotensin II was decreased in the cells from heparin-treated rats or in the heparin-treated cells. Scatchard analysis showed that the decrease in binding was due to a decrease in both the number and the affinity of angiotensin II receptors in the cells from heparin-treated rats and a decrease in the number, but not the affinity, of the receptors in the heparin-treated cells. Heparin also caused a decrease in the maximum angiotensin Il-induced production, but not the basal production, of aldosterone in the cells from heparin-treated rats and in the heparin-treated cells. These data suggest that heparin interacts with adrenal angiotensin II receptors to inhibit the angiotensin Il-induced aldosterone production.
Stimulation of aromatase activity in the fetal rat gonads by cAMP and FSH
Authors: Weniger J.-P. , Zeis A.
Published: December 2008

Abstract. The gonads from 17- to 21-day-old fetal rats were cultured in vitro in the presence of [3H]testosterone and in the presence or absence of cAMP or FSH, and estrone and estradiol formed were measured by double isotopic dilution and recrystallization to constant specific activity. Estrogen synthesis by testes was stimulated by both cAMP and FSH as early as at 18 days of gestation. FSH did not enhance aromatase activity in ovaries, although cAMP did. It is remarkable that FSH controls estrogen synthesis in the testis earlier than in the ovary.
Calcitonin-like immunoreactivity and calcitonin gene expression in the placenta and in the mammary gland of the rat
Authors: Jousset V. , Legendre B. , Besnard P. , Segond N. , Jullienne A. , Garel J.-M.
Published: December 2008

Abstract. Recently, the presence of monomeric CT in plasma and milk was reported by others in a lactating woman surgically thyroidectomized. Similarly, the placenta was thought to be a possible source of CT. Since such findings were based exclusively on immunological arguments, we have investigated the CT gene expression in these rat tissues. CT mRNAs were detected by dot-blot hybridization of total RNAs extracted from rat tissues with a 32P-labelled human CT cDNA probe. Subcellular fractions of each tissue were screened for CT-like immunoreactivity using two different antibodies. With one antibody, extracts of the mammary gland and placenta both produced full displacement of labelled human CT from the antiserum and serial dilutions of the extracts gave displacement curves parallel to that of synthetic human CT, which suggests immunological similarity. However, dilution curves were not parallel for the second antibody, and for both antisera, CT-like immunoreactivity was found in all subsellular fractions from nuclei to cytosols. Immunoprecipitation of translation products from poly (A)+RNAs of placenta showed two major bands around 30 kD. Under stringent conditions, the weak hybridization of placental RNAs seen by dot-blot under less stringent conditions disappeared. Northern analyses of total RNAs from the placenta failed to detect mRNA of 1 k base size like in thyroid glands, but hybridization under weak stringent conditions occurred with larger mRNAs (around 4.4 and 2.4 k bases). Immunoprecipitation of translation products from mRNAs of rat mammary glands showed three major bands around 46, 30 and 20 kD. Dot-blot hybridization of total RNAs extracted from mammary glands was also negative. In conelusion, our results suggest that the CT gene is not expressed in the rat placenta and in rat mammary gland, since CT mRNAs were not detected in either tissues.
Hormonal effects of CQP 201—403, a new dopamine agonist
Authors: Gaillard R. C. , Brownell J.
Published: December 2008

Abstract. CQP 201—403 is a propylergoline derivative with strong dopamine stimulant properties in animals models. It was developed in order to meet the need for a dopamine agonist compound which would offer longer action and improved tolerability. In this study, we tested CQP 201—403 in healthy male volunteers in order to assess its PRL suppression action and other hormonal effects as well as its duration of action and tolerability. Twenty-one volunteers participated in a dose-range study conducted according to a double-blind cross-over design with placebo control. The PRL suppression effect of single oral doses ranging from 0.05 mg to 0.035 mg were investigated. The duration of action of CQP 201—403 was tested in 6 other volunteers receiving a single oral dose of 0.025 mg or placebo. Blood was sampled over 48 h for PRL and GH measurements. An endocrine profile was performed in 6 volunteers receiving either 0.025 mg CQP 201—403 as a single oral dose or placebo. Blood was sampled over 8 h for measuring plasma PRL, GH, LH, FSH, TSH and cortisol. The results show strong dose-dependent PRL suppression (P< 0.001) begining 2 h after ingestion. PRL suppression lasted for more than 24 h and the normal sleep PRL surges were abolished. GH was transiently stimulated during the first few hours; the GH sleep profile was normal. All other hormones were not affected by the administration of CQP 201—403. Tolerability was good and no drug attributable changes in safety measures occurred. This study demonstrated that CQP 201—403 is a potent and long-acting PRL suppression compound in healthy volunteers. Strong PRL suppression and optimal tolerability were achieved with the 0.025 mg dose. This new dopamine agonist promises to be a therapeutically useful dopaminomimetic compound which could probably be prescribed at a once-daily dosage.
Hereditary pituitary prolactinomas: a new rat model
Authors: Chedid A. , Hoversland R. C. , Chejfec G. , McCune S. A. , Jurin R. R. , Evans E. E.
Published: December 2008

Abstract. Pituitary adenomas are known to occur spontaneously in several rat strains, especially during aging. Here we report the occurrence of adenomas (prolactinomas) in a new rat model at an early age. The adenomas were characterized by light and electron microscopy and histochemicaly by immunoperoxidase methods using specific antisera. Of the 53 pituitaries examined, one was normal, two were hyperplastic and the remainder were adenomas. Among the latter, there were 37 prolactinomas (70%), 3 GH-producing tumours and 2 ACTH-containing neoplasms. One microadenoma produced both PRL and GH. The remaining 8 adenomas were histochemically negative for all pituitary hormones. Serum PRL levels were elevated in both sexes while serum testosterone was high in females and low in the males. The serum estrogen levels were elevated in the males with prolactinomas. The prolactinomas appear to be transmitted as an autosomal dominant characteristic with incomplete penetrance and a greater incidence in the male.