bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian aromatase activity in scorbutic mutant rats unable to synthesize ascorbic acid
Authors: Tsuji Motomu , Ito Yasuhiro , Terada Nobuyuki , Mori Hiroshi
Published: December 2008

Osteogenic disorder syndrome rats are unable to synthesize ascorbic acid owing to the lack of l-gulonolactone oxidase, and become scorbutic within a few weeks without the supply of ascorbic acid. We studied effects of ascorbic acid deficiency on the ovarian aromatase activity in vivo using osteogenic disorder syndrome rats. The ovarian aromatase activity in ascorbic acid-deficient osteogenic disorder syndrome rats was significantly higher than that in normal or ascorbic acid-supplied osteogenic disorder syndrome rats. The activity in hypophysectomized immature rats was extremely low, but increased after treatment with pregnant mare serum gonadotropin, regardless of the presence or absence of ascorbic acid. The extent of the increase was the same among experimental groups. The present results indicate that ascorbic acid at physiological level lowers the ovarian aromatase activity, whereas it does not impair the responsiveness of the aromatase activity to gonadotropins.
Re-evaluation of eye muscle autoantibody determination in Graves' ophthalmopathy: failure to detect a specific antigen by use of enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoblotting techniques
Authors: Schifferdecker E. , Ketzler-Sasse U. , Boehm B. O. , Ronsheimer H. B. , Scherbaum W. A. , Schöffling K.
Published: December 2008

Sera from 41 patients with Graves' ophthalmopathy were investigated for presence of autoantibodies directed against eye muscle preparations using different methods: 1. ELISA with pork eye muscle membrane preparations; 2. Immunoblotting with glycoprotein preparations from human eye muscle; 3. Indirect immunofluorescence with human eye muscle sections. The ELISA was not suitable for detection of specific immunoglobulin binding with sera from patients suffering from endocrine ophthalmopathy. Immunoblotting exhibited only nonspecific binding to some muscle proteins; it could be prevented by pre-adsorption procedures and was not different from the pattern observed with skeletal muscle as antigen. The indirect immunofluorescence technique revealed no binding of Graves' sera to human muscle sections, whereas sera containing antibodies against skeletal muscle bound to eye muscle as well. Thus far, an antigenic structure of eye muscle specific for Graves' ophthalmopathy is not detectable with the methodology used here. The possibility that retroorbital connective tissue may be the main target of the autoimmune process must be considered.
Aromatase activity in purified Leydig cells from adult rat. Comparative effects of insulin, IGF-I, and hCG
Authors: Rigaudière Nicole , Grizard Geneviève , Boucher Daniel
Published: December 2008

The comparative effects of insulin and IGF-I on aromatization in adult rat purified Leydig cells were examined to elucidate the mechanism of action of the peptides in testicular steroidogenesis. Aromatase activity was measured in short-time incubations, using the tritiated water release method with [1β-3H] androstenedione as substrate. In the presence of varying concentrations of substrate, the apparent Km for androstenedione was 0.945 mol/1; treatment of cells with insulin, IGF-I and hCG markedly increased the apparent maximal velocity, without modifying Km; peptides were more potent in aromatase stimulation than hCG alone or in combination with either peptides. When related to time (0–4 h) and expressed as percent of control values, aromatase activity in the presence of insulin, IGF-I and/or hCG exhibited a significant and transient increase at 15–30 min. In order to clarify the nature of this early stimulation, the effects of dibutyryl cAMP, various antibiotics, and cytochalasin B on treated Leydig cells were analysed. Results indicated that insulin and IGF-I action on aromatization was not cAMP-dependent; peptides could intervene by increasing RNA and protein, but not DNA, synthesis; they were also effective in glucose transport. These data suggest that insulin and IGF-I are able to modulate aromatization in Leydig cells.
Role of testosterone in regulating the growth of mice from lines selected for low vs high plasma insulin-like growth factor-I concentrations
Authors: Siddiqui Rafat A. , McCutcheon Stuart N. , Mackenzie Duncan D. S. , Blair Hugh T. , Ormsby J. Eldon , Gluckman Peter D. , Breier Bernhard H.
Published: December 2008

A study was undertaken to investigate the role of testosterone in regulating growth and circulating levels of insulin-like growth factor-I in male mice from lines divergently selected on the basis of plasma IGF-I. Controls of each lines were sham-operated at 10 days of age and treated with peanut oil from day 14 to day 70. A second group, which was castrated at 10 days and treated with testosterone enanthate (0.5 μg · (g body weight) −1 · day−1) from day 14 to 70, did not differ from controls in body weight but had higher plasma IGF-I concentrations. Delaying testosterone therapy until day 42 in a third group retarded growth, with body weights being significantly lower than those of other two groups from days 35 to 56. However, plasma IGF-I levels in this group were not different from those of controls. Effects of line and treatment were additive. It is concluded that the greater pubertal growth of high-line compared to low-line males is not due to greater stimulation of circulating IGF-I by testosterone. Furthermore, testosterone does not appear to influence pubertal growth by acting on circulating levels of IGF-I.
The respective effects of serum thyroxine and triiodothyronine on serum thyrotropin and lipid parameters in endemic juvenile hypothyroidism
Authors: Smitz J. , Vanderpas J. , Yunga Y. , Bourdoux P. , Gerlo E. , Sevens C. , Thilly C. H.
Published: December 2008

The respective effects of serum total T4 concentration and of serum total T3 concentration on serum TSH concentration and on lipid parameters were compared in 84 7- to 16-year-old children of the Northern Zaire goitre endemia classified in group A (T4 > 77 nmol/l and T3 > 1.69 nmol/l), B (low T4, normal T3) and C (low T4, low T3). Mean serum TSH level was normal in group A (2.3 mU/l), it raised to 39.4 mU/l in group B (p < 0.001) and to 166.3 mU/l in group C (p < 0.001 vs A and B). Low density lipoprotein cholesterol and apoprotein B were increased in group B vs A (p < 0.05) and in group C vs A (p < 0.001) and B (p < 0.001 for apoprotein B; not significant for cholesterol). High density lipoprotein cholesterol and apoprotein Al were similar in the three groups. Mean serum triglyceride level, not different in groups A and B, was doubled in group C (p < 0.001). Multiple regression analysis showed that serum TSH, apoprotein B, and triglyceride levels were influenced by both thyroid hormones concentrations with a predominant effect of serum T4 on the first two parameters and of serum T3 on the last one. In conclusion, low serum T4 with normal T3 concentrations resulted in an increase in serum TSH and in an altered lipid metabolism; it clearly represented an hypothyroid state.
Decreased glucagon binding and glucagon-stimulated lipolysis in adipocytes from streptozotocin-diabetic rats
Authors: Sato Nobuyuki , Irie Minoru , Kajinuma Hiroshi , Suzuki Kazuo
Published: December 2008

Adipocytes from streptozotocin-diabetic rats showed a markedly reduced lipolytic response to glucagon concomitant with a 90% or greater decrease in the number of glucagon receptors per cell. In contrast, β-adrenergic receptors assessed by [3H]dihydroalprenolol binding and lipolysis stimulated by isoproterenol, dibutyryl 3′5′-cyclic AMP and 3-isobutyl-1-methylxanthine were reduced by only 10–25% in diabetic rats compared with controls. Furthermore, quantitative analysis of the relationship between the amount of cell-bound glucagon and the hormone-stimulated lipolysis revealed that the function of the remaining 10% of glucagon receptors remained intact in cells from diabetic animals. These findings suggest that the lipolytic cascades, including β-adrenergic receptors, in adipocytes are not greatly impaired by diabetes, and therefore, the unresponsiveness of these cells to glucagon is mostly due to a marked reduction in the number of glucagon receptors, probably as a result of a down-regulation by postprandial hyperglucagonemia.
Effect of isoprenaline on the output of melatonin from fetal and newborn lamb pineal glands in vitro
Authors: McMillen I. C. , Parkington H. C. , McCance I.
Published: December 2008

We have measured the output of melatonin in vitro from the pineal glands of lambs in late gestation (135–143 days) and the early newborn period (4–8 days). The basal output of melatonin/mg pineal tissue was significantly lower in the fetal group (16.3 ± 3.9 pg melatonin · (30 min)−1 · mg−1) than in the newborn group (148.1 ± 43.6 pg melatonin · (30 min)−1 · mg−1). Addition of the β-adrenergic agonist, isoprenaline (10−5 mol/l) significantly stimulated melatonin output from both the fetal (to 24.9 ± 3.9 pg melatonin · (30 min)−1 · mg−1) and newborn pineals (to 247.7 ± 67.3 pg melatonin · (30 min)−1 · mg−1). Pineals from newborn lambs produced 9–10-fold more melatonin than the fetal pineal glands, before, during and after addition of isoprenaline. These results show that functional β-adrenergic receptors are present before birth on the sheep pinealocyte and that there is a marked increase in the melatonin synthetic capacity of the pineal in the newborn period.
Arginine vasopressin secretion in non-obese women with polycystic ovary syndrome
Authors: Coiro V. , Volpi R. , Capretti L. , Bacchi-Modena A. , Cigarini C. , Bianconi L. , Rossi G. , Gramellini D. , Chiodera P.
Published: December 2008

Arginine vasopressin responses to osmotic (0.1 ml · kg−1 · min−1 NaCl), orthostatic (standing upright and maintenance of orthostatic position for 20 min), and hypoglycemic (0.15 IU/kg insulin) stimuli were evaluated in women with polycystic ovaries and in normal subjects. Blood dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, testosterone, cortisol, and endogenous insulin levels were significantly higher in women with polycystic ovaries than in controls, whereas estrone, estradiol-17β, progesterone and 17OH-progesterone concentrations were normal in all subjects. Arginine vasopressin basal levels (mean ± sem of 3 test days; women with polycystic ovaries: 2.8 ± 0.2 pmol/l; controls: 2.7 ± 0.2 pmol/l) and secretory responses to orthostatic (mean peaks 100% higher than baseline values) and to hypertonic (130% increments) stimuli were similar in the two groups. Arginine vasopressin responses to hypoglycemia were lower in women with polycystic ovaries (50% increment) than in controls (150% increment), although comparable blood glucose decrements and GH or cortisol increments were found in the two groups. Arginine vasopressin peak responses to hypoglycemia were negatively correlated to testosterone, androstenedione, and endogenous insulin levels, but did not correlate with basal and hypoglycemia-induced peak cortisol concentrations or with circulating levels of other steroids. These data indicate a hypothalamic posterior pituitary disorder affecting arginine vasopressin response to insulin-induced hypoglycemia in women with polycystic ovaries syndrome associated with elevated blood androgen and insulin concentrations.
Neutrophil chemotaxis, random migration, and adherence in patients with hyperthyroidism
Authors: Wolach B. , Lebanon B. , Jedeikin A. , Shapiro M. S. , Shenkman L.
Published: December 2008

We have examined neutrophil adherence, chemotactic activity, and random migration in 35 hyperthyroid patients with Graves' disease and 106 normal volunteers. No statistically significant differences were found between granulocyte adherence of 17 hyperthyroid subjects (67 ± 15.6%) and 81 healthy volunteers (63.1 ± 17%). In 3 thyrotoxic patients, impaired neutrophil adherence was found, which resolved when thyroid function returned to normal. The neutrophil chemotactic activity of 32 normal controls was 107.5 ± 21.4 cells, and the random migration 36 ± 15.5 cells. No statistically significant difference was demonstrated in 13 hyperthyroid patients who had a neutrophil chemotactic activity of 102 ± 14.6 cells and a random migration of 31.2 ± 13.2 cells. Defective chemotactic activity and random migration was found in 2 patients. Neutrophil functions returned to normal in one of the two subjects who were re-evaluated when thyroid function recovered. In summary, 14% of hyperthyroid patients had impaired leukocyte functions. However, severe pyogenic infections are quite rare in hyperthyroid patients, indicating that the observed alterations in function of phagocytic cells are not clinically important.
Induction of experimental thyroiditis in mice by recombinant interferon γ administration
Authors: Kawakami Yasushi , Kuzuya Nobuaki , Watanabe Tsuyoshi , Uchiyama Yasuo , Yamashita Kamejirou
Published: December 2008

Expression of major histocompatibility complex (MHC) class 2 molecules on the thyroid follicular cells in human autoimmune thyroid diseases has been reported, and is suggested to play a role in the initiation of the autoimmune responses. Interferon γ is known to induce MHC class 2 molecules on cultured thyrocytes. Therefore, we administered recombinant interferon γ to mice to induce MHC class 2 molecule expression in vivo, and investigated the thyroidal changes following MHC class 2 molecule expression. Recombinant interferon γ3 × 105 U, was administered daily, to mice. MHC class 2 molecules, studied by indirect immunohistochemistry, were expressed on the follicular cells on the 2nd to 4th day after the first interferon γ administration and continued thereafter. Serum T4 and T3 concentrations decreased and anti-thyroglobulin antibodies and anti-microsomal antibodies were detected. Lymphocyte infiltrations were observed in the thyroid glands obtained at 28 days, but they were mild. These results suggest that MHC class 2 molecule expression on thyroid follicular cells induces anti-thyroid antibodies and plays an important role in the initiation of autoimmune thyroiditis. However, the progression of the immune response to thyroiditis with lymphocyte infiltration may require some other factor. This new model of autoimmune thyroid disease in mice might be useful to elucidate the pathogenesis of human autoimmune thyroid diseases.
The prolactin releasing effect of histamine is unrelated to its vascular action
Authors: Kjær Andreas , Knigge Ulrich , Warberg Jørgen
Published: December 2008

We investigated in male rats whether the prolactin releasing effect of systemically infused histamine might be attributed to a vasodilatatory action of the compound. Intraarterial infusion of histamine (3.8 μmol) over 1 min increased the plasma PRL 10-fold. This effect was prevented by prior ia infusion of the H1 receptor antagonist mepyramine and slightly augmented by prior ia infusion of the H2 receptor antagonist cimetidine. At the same time histamine caused an immediate 38% decrease in mean arterial blood pressure, which remained 15% below the initial level during the rest of the 60-min observation period. The depressor effect of histamine was prevented by pretreatment with mepyramine and partly prevented for the first 5 min by pretreatment with cimetidine. Since the H1 receptor seemed to be the predominant mediator of the histamine-induced hypotension and PRL release, a causative interaction is possible. However, when the histamine-induced decrease in blood pressure was prevented by simultaneous iv loading with saline the PRL response to histamine was still evident. Furthermore, when the histamine-induced decrease in blood pressure was mimicked by ia infusion of the vasodilator nitroprusside no effect was observed on PRL secretion. We conclude that the histamine-induced stimulation of PRL secretion is independent of the profound depressor action of the amine.
Enhanced testosterone secretion in adult rams after establishment of a high-frequency, low-amplitude pattern of LH pulses in the nonbreeding season occurs without changes in the number or binding affinity of testicular LH receptors
Authors: Sanford Lee M. , Baker Susan J.
Published: December 2008

When the LH signal in the ram is changed from one of large and infrequent pulses to one of small and frequent pulses, the testes quickly become more responsive to LH and testosterone secretion is elevated, perhaps because the number and (or) binding affinity of testicular LH receptors have increased. An experiment was undertaken in the nonbreeding season (July) with 10 adult Dorset × Leicester × Suffolk rams that were about 3.5 years of age and 69 ± 2 kg in body weight. Rams were given injections into the jugular vein of either 5 μg NIH-LH-S24 (in 1 ml saline) or vehicle every 80 min for 6 days. LH treament produced a series of LH pulses that occurred three times more frequently and were 70% less in amplitude than pulses in the control rams, without causing mean LH concentration to increase. Endogenously produced LH pulses were not evident in the treated rams after LH injection began. The modified LH-pulse pattern elevated mean testosterone concentration by 150% (assessed on days 2 and 5), and caused the cumulative testosterone response to LH pulses, estimated by multiplying testosterone-pulse amplitude by frequency per 6 h, to increase progressively by 180% (days −2 through 5). Enhanced testicular steroidogenic activity, presumably due to greater enzymatic activity and cholesterol availability within Leydig cells, was not associated with increases in either the concentration or affinity of LH-binding sites in the testis (assessed on days 3 and 6).
Serum testosterone levels in women with Cushing's disease
Authors: Halpin David M. G. , Burrin Jacky M. , Joplin Graham F.
Published: December 2008

Serum testosterone was measured pre- and post-operatively in 31 women who obtained remission of Cushing's disease following treatment by interstitial irradiation of the pituitary gland. The mean serum testosterone was initially elevated at 3.35 nmol/l, with values ranging from 0.7 to 14.4 nmol/l. Following treatment the mean serum testosterone fell to 1.42 nmol/l (i.e. normal) and all but one of the 15 patients with initially elevated pre-treatment values obtained normal levels. The pre-treatment testoterone concentrations correlated significantly (r = 0.47; p = 0.019) with the midnight ACTH concentration. The likely determinant of the raised serum testoterone would appear to be the intensity of the ACTH drive, although an individual's inherent sensitivity to ACTH may also be a factor.
Episodic nyctohemeral secretion of melatonin in adult humans: Lack of relation with LH pulsatile pattern
Authors: de Leiva Alberto , Tortosa Federico , Peinado Miguel A. , Serrano José , Rodriguez-Espinosa José , Puig-Domingo Manuel
Published: December 2008

The concentration of melatonin and LH were determined in plasma samples obtained at 10-min intervals during 4 h of darkness (00.00-04.00 h) from 4 normal women, age 23-27 years, in the early follicular phase of the menstrual cycle and in 6 normal men, age 23-31 years. Additionally, melatonin concentration was determined in samples obtained from the men at 10-min intervals for 4 h during the day (10.00-14.00 h). A pulsatile pattern of melatonin secretion was found for all the subjects during darkness. There was no significant difference between women and men as to the number of pulses (2.8 ± 0.5 vs 5.2 ± 1.0 per 4 h), amplitude of pulses (51.3 ± 28 vs 27.2 ± 6 ng/l), concentration per 4 h (32.5 ± 13 vs 31.0 ± 5 ng/l), or apparent half-life of melatonin (19.3 ± 2.3 vs 15.3 ± 7.5 min). The mean amplitude of the melatonin pulse correlated (r = 0.863, p<0.001) with the mean melatonin concentration per 4 h. A pulsatile LH secretion pattern was found for the 10 subjects and did not correlate significantly with the melatonin secretion pattern. The results are consistent with an independent signal for the demonstrated nyctohemeral pulsatile melatonin and LH secretions.
The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man
Authors: Philipsen E. K. , Myhre J. , Larsen S. , Nielsen M. Damkjær , Holst J. J. , Hilsted J.
Published: December 2008

To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the angonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and betahydroxy butyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.
Long-term culture of rat mammotrope and somatotrope subpopulations separated on continuous Percoll density gradients: Effects of dopamine, TRH, GHRH and somatostatin
Authors: Hofland Leo J. , van Koetsveld Peter M. , Verleun Theo M. , Lamberts Steven W. J.
Published: December 2008

Normal adult female rat mammotrope and somatotrope subpopulations were separated on continuous Percoll density gradients according to differences in their density. Viable cells were recovered in 16 fractions. The cells from each fraction were cultured during 7 days after which period 4-h incubations were performed. rPRL secretion per cell increased towards the higher density fractions. No major difference in TRH, dopamine and somatostatin responsiveness was observed between mammotropes that were recovered in the different gradient fractions. In addition, no differences in somatostatin responsiveness between the somatotrope cells in the different gradient fractions were observed. However, somatotropes that were recovered in the highest density region of the gradient appeared to be more responsive to GHRH than the lower density somatotropes. In the various gradient fractions there were no paradoxical effects of TRH and dopamine on rGH release and of GHRH on rPRL release. Conclusions: 1. In long-term cultures there is no evidence for functionally different subpopulations of mammotropes and somatotropes, separated according to differences in their density, with regard to dopamine and TRH responsiveness and with regard to somatostatin responsiveness, respectively. 2. There is no evidence for a (mammosomatotrope?) subpopulation of cells showing paradoxical responses of PRL or GH release to GHRH and dopamine or TRH, respectively.
Pituitary repetitive stimulation with GnRH/TRH in women treated with three different oral steroid contraceptives
Authors: Pérez-López Faustino R.
Published: December 2008

Twelve untreated cycling women and 45 women using oral contraceptives were challenged iv with 50 μg of GnRH and 100 μg of TRH at 0, 90 and 180 min. The LH responses after the second and third pulses of GnRH/TRH were diminished in women treated with 30 μg of ethinylestradiol and levonorgestrel as compared with the control group, whereas the responses were severely blunted after each dose of GnRH/TRH in women treated with 50 μg of ethinylestradiol and levonorgestrel or lynestrenol as compared with both the control group and the women treated with 30 μg of ethinylestradiol and levonorgestrel. The FSH responses to GnRH/TRH in women treated with 30 μg of ethinylestradiol and levonorgestrel were similar to those in the control group, whereas there were reductions in the responses obtained in women treated with 50 μg of ehinylestradiol and progestin as compared with both the control group and the women under 30 μg of ethinylestradiol and levonorgestrel. In women treated with 30 μg of ethinylestradiol and levonorgestrel, the PRL peaks after the second and third pulses were higher than the first, and higher than the values obtained in the remaining three groups.
Tissue-specific differences in the compartmentalization of rat nuclear triiodothyronine receptors
Authors: Barsano Charles P. , Iqbal Zafar , Pullen Gordon L. , Muñoz B. Elena , Singh Sant P.
Published: December 2008

In addition to the recognized rat liver nuclear T3 receptor extractable with hypertonic salt, recent studies have described nucleoplasmic receptors extractable with isotonic KCl and salt-resistant receptors localized to the nuclear matrix. A method was developed for the determination of intra-nuclear receptor distribution 1in small samples of nuclei dispersed within glass wool matrices. After in vitro labelling with 6 nmol/l [125I]T3, dispersed nuclei were sequentially extracted with 0.15 mol/l KCl (yielding nucleoplasmic receptors), 0.4 mol/l KCl, and 2 mol/l KCl (the latter two concentrations yelding hypertonic salt-extractable receptors). The salt-resistant receptors were retained within the glass wool columns. The intra-nuclear distribution of in vivo labelled receptors was very similar to that obtained by in vitro labelling. The equilibrium association constants for L-T3 binding among the receptor pools ranged from 0.6 × 109 to 1.0 × 109 l/mol. The distribution of total nuclear receptors within each nuclear compartment was (percentage of nucleoplasmic, hypertonic salt-extractable, and salt-resistant receptors): Cerebrum: 23.6, 52.2, 24.2; Liver: 25.2, 57.2, 17.5; Kidney: 45.9, 33.5, 20.6; Testis: 65.5, 14.7, 19.7; and Spleen: 66.7, 18.7, 14.6. The rank order of percentage of hypertonic salt-extractable receptors approximates the rank order of thyroid hormone-responsiveness by traditional criteria. The inverse is true for the percentage of nucleoplasmic receptors. The percentage of salt-resistant receptors was very similar in all of the tissues.
Effects of a dopamine antagonist (metoclopramide) on the release of LH, FSH, TSH and PRL in normal women throughout the menstrual cycle
Authors: Seki Katsuyoshi , Nagata Ichiro
Published: December 2008

To obtain further insight into the role of endogenous dopamine on the adenohypophyseal hormones secretion in normal women, responses of the adenohypophyseal hormones to a dopamine antagonist, metoclopramide, were evaluated in 7 normal women during the early follicular, late follicular and mid-luteal phases of the menstrual cycle. PRL increments following metoclopramide were similar in all phases. During the early and late follicular phases, metoclopramide induced no significant change in circulating LH levels. However, a significant rise in serum LH was observed following metoclopramide during the mid-luteal phase. No significant changes in serum FSH levels were observed after metoclopramide during any of the 3 phases of the cycle. Following metolopramide, serum TSH levels significantly rose in all phases. TSH increments following metoclopramide were significantly lower in the mid-luteal phase than in the early follicular phase. These results suggest that the modulatory effect of endogenous dopamine on adenohypophyseal hormones secretion is variable and selective throughout the normal menstrual cycle.
Development of a sensitive enzyme immunoassay for LH determination in bovine plasma using the streptavidin-biotin technique
Authors: Mutayoba B. M. , Meyer H. H. D. , Schams D. , Schallenberger E.
Published: December 2008

Using the biotin-streptavidin amplification technique, highly sensitive specific second-antibody enzyme immunoassays for determining LH in bovine plasma with long (48 h) and short (4 h) incubation periods were developed. Biotin was linked to bLH by the N-hydroxysuccimidine method and the product (biotinyl-bLH) used to bridge between streptavidin-peroxidase and the immobilised bLH antibody in competitive tests. The assays were validated and their performance compaired with a radioimmunoassay currently in use. The sensitivities of the long and short incubation enzyme immunoassays (8 pg and 15 pg/well, respectively) were superior to that of 5-day incubation radioimmunoassay (100 pg/tube). Plasma interference in both assays were acceptable and volumes of 5 to 40 μl gave parallel standard curves and comparable LH levels, 10–20 μl plasma was sufficient to measure LH baseline levels by the long incubation enzyme immunoassay. The mean recovery of added standard bLH to plasma samples containing different endogenous LH was >90% (range 91.7–112) in both assays. The intra- and inter-assay variations of both assays were less than 10 and 17%, respectively. When both enzyme immunoassay and radioimmunoassay were used to measure LH in cyclic cows, the basal levels measured by enzyme immunoassay were lower than that measured by radioimmunoassay. Enzyme immunoassay offers an attractive alternative to the lengthy radioimmunoassay in current usage, with an added advantage of employing non-isotopic label.
Peripheral blood T cell activation after radioiodine treatment for Graves' disease
Authors: Teng Wei-Ping , Stark Roger , Munro AlistairJ. , Young Stuart McHardy , Borysiewicz Leszeck K. , Weetman Anthony P.
Published: December 2008

Radioiodine therapy for Graves' thyrotoxicosis produces a rise in thyroid autoantibodies in the first three months after treatment, but little is known of its effects on T cells. We have therefore followed the changes in T cell subsets in sequential samples from 23 patients with Graves' disease treated with radioiodine, using dualcolour flow cytometry. In the first month after treatment there was a significant rise in activated T cells, identified by the markers HLA-DR (la) and CDw26/Tal (p<0.025 in both cases). CD45RO-positive T cells, which are the primed population containing memory cells, also increased (p<0.025), but there was no change in CD45R-positive, resting T cells or in the CD4 to CD8 (helper to cytotoxic/suppressor) ration. Vicia villosa-binding T cells, containing the contrasuppressor population, showed a more variable response, but the trend was to an overall increase from pre-treatment values (p<0.025). The changes did not appear to be related to antithyroid drug treatment, since they were seen irrespective of whether patients continued such therapy. These results suggest that T cell activation and enhanced contrasuppressor activity may in part be responsible for the rise in autoantibodies after radioiodine. The T cell changes could also contribute to the worsening of ophthalmopathy seen in some radioiodine-treated patients.
Postpartum thyroid dysfunction in Bangkok: A geographical variation in the prevalence
Authors: Rajatanavin Rajata , Chailurkit La-or , Tirarungsikul Kanokporn , Chalayondeja Wirawat , Jittivanich Uraiwan , Puapradit Winit
Published: December 2008

To determine the prevalence of thyroid dysfunction in Thai postpartum women, we evaluated thyroid function and thyroid autoantibodies in 812 consecutive unselected women at 1.5 months post partum. At 3.5 months post partum 570 women without previous thyroid abnormality returned for a second set of thyroid function test. The prevalence of thyroid dysfunction was 1.1%, which was less than that reported from other countries. Various types of postpartum thyroid dysfunction, namely, transient thyrotoxicosis followed by transient hypothyroidism, transient thyrotoxicosis or hypothyroidism occurring alone or permanent hypothyroidism were encountered. Eight out of 9 patients with thyroid dysfunction had thyroid autoantibodies. Fine needle aspiration biopsy of the thyroid was done in 4 patients and all showed lymphocytic thyroiditis. Even though Bangkok is an iodine surfeit area, iodine intake is relatively lower than in other areas where the prevalence of postpartum thyroid dysfunction is much higher. The discrepancy in geographic prevalence of postpartum thyroid dysfunction may result from the interaction of immunogenetic heterogeneity of different ethnic background, environmental iodine intake, and other unidentified environmental factors.
Hypoglycemia owing to inappropriate glucagon secretion treated with a continuous subcutaneous glucagon infusion system
Authors: Abs Roger , Verbist Louis , Moeremans Marleen , Blockx Pierre , De Leeuw Ivo , Bekaert Jozef
Published: December 2008

A selective glucagon deficiency was documented in a 36-year-old female patient suffering from severe hypoglycemic attacks. The extremely low fasting plasma glucagon levels could not be stimulated by hypoglycemia. The increase in plasma glucagon during stimulation with arginine did not prevent hypoglycemia provoked by the simultaneous insulin secretion. Treatment consisting of a continuous sc glucagon infusion system resulted in correction of both postabsorptive and postprandial hypoglycemia. Further lowering of the glucose level during an arginine test could be the hallmark of this hypoglycemic syndrome characterized by an inappropriate glucagon secretion. This case report would indicate that epinephrine cannot prevent hypoglycemia when glucagon release is completely deficient.
The effect of orchidectomy on rat pituitary responsiveness to GHRH depends on age
Authors: Pinilla L. , López F. J. , Aguilar E.
Published: December 2008

Pituitary responsiveness to GHRH (1-29) NH2 (GHRH, 5 μg/kg iv) was analysed under sodium pentobarbital anesthesia (50 mg/kg ip), on days 30 and 90 in male rats orchidectomized or sham-operated 7 days earlier. Other groups of rats were orchidectomized or shamoperated on day 23 and tested on days 30, 45, 60 and 90. In the sham-operated animals, GHRH stimulated GH secretion on day 90, but not on day 30. GHRH-induced secretion was similar on days 45, 60 and 90 in orchidectomized and sham-operated animals. Orchidectomy on day 83 reduced this GHRH-induced GH secretion on day 90. In contrast, orchidectomy on day 23 enhanced the pituitary responsiveness to GHRH a week later. These results suggest that the increase in pituitary responsiveness to GHRH with age is independent of the testicular function and that the effect of orchidectomy depends on both the age of the rats at orchidectomy and the time elapsed between the orchidectomy and the administration of GHRH.
Histamine-induced paradoxical GH response to TRH/GnRH in men and women: Dependence on gonadal steroid hormones
Authors: Knigge Ulrich , Thuesen Benedikte , Dejgaard Anders , Svenstrup Birgit , Bennett Paul
Published: December 2008

A stimulatory GH response to TRH and GnRH occurs frequently in patients with various pathological conditions, but is absent in normal subjects. We have previously shown that histamine induced a paradoxical GH response to TRH in normal men. Since gonadal steroids influence GH secretion, we investigated whether infusion of histamine might induce a GH response to combined administration of TRH (200 μg) and GnRH (100 μg) in 6 normal women during the early follicular and luteal phase of the same menstrual cycle and in 7 normal men. Histamine had no effect on basal GH secretion in men or in women during the two phases of the menstrual cycle. However, compared with saline, histamine induced a GH response to TRH/GnRH in men (GH peak: 5.5 ± 1.0 vs 1.4 ± 0.3 μg/l; p<0.01) and in women during the luteal phase (GH peak: 5.2 ± 1.6 vs 1.5 ± 0.4 μg/l; p<0.025), but not during the early follicular phase of the cycle (GH peak: 1.7 ± 0.5 vs 1.6 ± 0.3 μg/l). In luteal-phase women the GH response to TRH/GnRH correlated with the serum estradiol-17β level (GH area/E2: r=0.98; p<0.005) and the serum estrone level (GH area/E1: r=0.81; p<0.05). In men the GH response to TRH/GnRH did not correlate with estrogen or androgen levels. We conclude that high physiological levels of estrogens are pertinent to the activation of a histamine-induced GH response to TRH/GnRH in women, whereas the role of androgens and estrogens for the induction of the response in men seems more complex. Furthermore, the study indicates that histamine may increase the sensitivity of GH release to nonspecific stimuli.
Kidney tissue insulin-like growth factor I and initial renal growth in diabetic rats: Relation to severity of diabetes
Authors: Flyvbjerg Allan , Ørskov Hans
Published: December 2008

The initial renal hypertrophy in experimental diabetes is dependent on the prevailing blood glucose level and is associated with renal accumulation of insulinlike growth factor I. To investigate the relationship of blood glucose to kidney IGF-I, a graded range of diabetic aberration was established in young rats by iv injection of increasing amounts of streptozotocin (25–80 mg/kg) at day 0. In 30 diabetic rats the mean of day 1 and day 2 blood glucose concentrations ranged from 6.2 to 32.0 mmol/l and 24-h urinary glucose excretion (24–48 h) from 0.04 to 43.3 mmol/24 h. The right kidneys were removed after 48 h, weighed and their IGF-I concentration analysed by radioimmunoassay. Kidney IGF-I was positively correlated to blood glucose (r = 0.66, p<0.0001) as well as to 24-h urinary glucose output (r = 0.54, p<0.005). At this early stage, kidney weight already correlated to blood glucose (r = 0.60, p<0.0005). No relationship between kidney IGF-I and kidney weight was found. However, if animals with severe diabetes were excluded, a significant correlation could be established (r = 0.51, p = 0.01, N = 24). The results support the hypothesis that IGF-I plays a causal role in the initial renal hypertrophy of experimental diabetes.
Relaxin and prostaglandin on oxytocin secretion from bovine luteal cells during different stages of gestation
Authors: Musah Al-Hassan I. , Schwabe Christian , Anderson Lloyd L.
Published: December 2008

The objective of this study was to determine whether bovine luteal cells from different stages of gestation secrete oxytocin and whether relaxin, cloprostenol (a potent analogue of prostaglandin F2α), estradiol-17β, and LH can acutely alter oxytocin secretion. Bovine luteal cells (105) were cultured for 24 h without treatment and with medium-hormone replacement every 24 h. Oxytocin was quantified by radioimmunoassay of the culture media. Basal oxytocin secretion was similar (22-31 pmol/l, p>0.05) for all stages of gestation (days 100, 145, 160, 185, 200, 210, and 240). Relaxin induced a dose-dependent suppression of oxytocin release. After 24 h of incubation, addition of 0, 16.7, 83.5, and 167 nmol/l porcine relaxin (3000 U/mg) induced 54 ± 4, 105 ± 16, 47 ± 4, and 38 ± 4 pmol/l of oxytocin in cells from 160-day-old corpora lutea and 138 ± 12, 21 ± 2, 19 ± 3, and 15 ± 2 pmol/l oxytocin in cells from 240-day-old corpora lutea. From luteal cells of 160- and 240-day-old corpora lutea, 2 μmol/l cloprostenol induced a marked increase (p<0.01) of 208 ± 39 and 371 ± 34 pmol/l oxytocin, respectively. Addition of 167 nmol/l relaxin did not prevent cloprostenol-induced oxytocin secretion during the first 48 h, but a decrease (p<0.05) in oxytocin occurred in day 3 cell cultures. These results indicate that cultured luteal cells obtained from different stages of gestation in cattle can secrete oxytocin and suggest a role for relaxin in the regulation of oxytocin release.
Cell metabolic activity in acromegaly: a microcalorimetric study of lymphocyte metabolism
Authors: Valdemarsson Stig , Ikomi-Kumm Julie , Monti Mario
Published: December 2008

A discrepancy between the clinical impression of disease activity and basal serum levels of growth hormone is often seen in patients with acromegaly. A slightly better relation has been found to serum levels of IGF-I, but a technique for evaluation of cell metabolic activity in this disease is still missing. For this purpose we used microcalorimetry to determine heat production rate in lymphocytes from 15 patients with acromegaly. The mean heat production rate was 2.90±0.15 pW/cell, significantly higher than in 13 healthy subjects, 2.31±0.12 pW/cell (p<0.01). Heat production rates did not correlate significantly with basal growth hormone levels, but increased, in a statistically significant manner (p<0.001), in parallel with the score index used to evaluate the clinical activity of the disease. Using the technique of microcalorimetry we could thus demonstrate an increased metabolic activity at a cellular level in patients with acromegaly, a finding that is in accordance with the view that an increased cell metabolic activity is a component of the disease process in acromegaly.
Prompt recovery of plasma arginine vasopressin in diabetic coma after intravenous infusion of a small dose of insulin and a large amount of fluid
Authors: Ishikawa San-e , Saito Toshikazu , Okada Koji , Nagasaka Shoichiro , Kuzuya Takeshi
Published: December 2008

We studied the changes in plasma arginine vasopressin in 5 patients with diabetic ketoacidosis and one patient with non-ketotic hyperosmolar coma who had marked hyperglycemia (36.6 ± 4.6 mmol/l, mean ± sem) and dehydration. Plasma osmolality (Posm) was 342.2 ± 11.4 mOsm/kg H2O, and hematocrit, serum protein, and blood urea nitrogen were also elevated at hospitalization. Circulating blood volume was decreased by approximately 21% as compared with that on day 7. Plasma AVP level was increased to 8.5 ± 1.6 pmol/l at hospitalization. When hyperglycemia was improved by iv infusion of a small dose of insulin plus fluid administration, plasma AVP level promptly decreased to 2.4 ± 0.4 pmol/l within six hours. When plasma AVP level had normalized, Posm was still as high as 305 mOsm/kg H2O, but the loss of circulating blood volume was only 4.2% of the control state. Plasma AVP level was positively correlated with change in hematocrit (plasma AVP = 3.58 + 0.45 · hematocrit, r = 0.468, p < 0.01), serum protein (r = 0.487, p < 0.01), Posm (r = 0.388, p < 0.01), and blood glucose (r = 0.582, p < 0.01). Plasma AVP level was negatively correlated with the change in circulating blood volume (plasma AVP = 3.6 – 0.14 · change in circulating blood volume, r = −0.469, p <0.01). These results indicate that both non-osmotic and osmotic stimuli are involved in the mechanism for AVP release in patients with diabetic coma, and that the non-osmotic control of AVP may contribute to circulating homeostasis, protecting against severe blood volume depletion in diabetic patients suffering from hyperglycemia and dehydration.
Thyrotropin releasing hormone does not stimulate prolactin release in the preterm human fetus
Authors: Roti Elio , Gardini Eliana , Minelli Roberta , Bianconi Lina , Alboni Alessandro , Braverman Lewis E.
Published: December 2008

Previous studies have suggested that fetal PRL secretion does not respond to stimuli such as TRH, metoclopramide, and cimetidine. It was postulated that the lack of response to TRH could be due to the possibility that, in the term fetus, lactotropes secrete PRL maximally and would be unresponsive to further stimulation. In order to study this hypothesis, 200 μg TRH or saline were administered to preterm pregnant women in labor. Maternal blood was obtained before TRH and saline administration. Maternal and cord blood were obtained at parturition. PRL, TSH, T4 and T3 concentrations were measured in all sera. TRH administration induced a significant increase in maternal serum PRL, TSH and T3 concentrations. In the cord blood of newborns whose mothers received TRH, serum TSH, T4 and T3 concentrations were significantly higher than in cord blood of newborns whose mothers received saline. Cord blood serum PRL concentrations were unchanged after TRH administration. This latter finding suggests that fetal lactotropes do not respond to TRH in the preterm fetus. Desensitization of fetal PRL secreting cells to TRH stimulation and/or the inhibitory effect of elevated fetal circulating corticosteroids on TRH-induced PRL secretion may explain the absent PRL response to TRH during fetal life.
Thyroid-stimulating antibody and thyrotropin-binding inhibitory immunoglobulin activity in hypothyroid patients who subsequently developed thyrotoxicosis
Authors: Tamai Hajime , Kasagi Kanji , Mizuno Osamu , Kobayashi Nobuyuki , Komaki Gen , Matsuzuka Fumio , Kuma Kanji , Konishi Junji , Kumagai Lindy F. , Nagataki Shigenobu
Published: December 2008

Although abnormal thyroid-stimulating and -blocking antibodies have been demonstrated in hyperthyroid and hypothyroid patients with autoimmune thyroid disorders, a direct correlation is not always observed. Thyroid-stimulating antibody, thyrotropinbinding inhibitory immunoglobulin, and thyroid-stimulating blocking antibody levels were determined in three hypothyroid patients who subsequently developed hyperthyroidism. Thyroid-stimulating antibodies levels were normal in one, elevated in another, and unmeasured in the third hypothyroid patient, but became elevated in all patients with the onset of hyperthyroidism. There was discordance, however, in one patient who had markedly elevated thyroid-stimulating antibodies and TSH-binding inhibitory immunoglobulin levels when she was hypothyroid. The data indicate that thyroidal responses to the abnormal stimulating antibodies may differ among patients with autoimmune thyroid disease.
Biosynthetic response of mouse intermediate pituitary gland to induced drinking and dehydration
Authors: Leenders HansJ. , de Vries TacoJ. , v. d. Loop Frank T. L. , Jenks Bruce G.
Published: December 2008

There are indications that the intermediate lobe peptide α-MSH is involved in the regulation of the hydromineral balance in mice and other mammals. The purpose of our studies was to determine whether manipulation of this balance in the mouse could lead to changes in either the rate of POMC biosynthesis in the pars intermedia or to changes in the direction of the processing of the precursor protein to form bioactive peptides. The results show that excess drinking, induced by substitution of drinking water by a 5% glucose solution, causes a rapid increase in POMC synthesis, whereas dehydration has the opposite effect; no evidence could be found that the above treatments have any effect on the processing of POMC, although strain differences were found in level of N-terminal acetylation of newly synthesized melanotropins and endorphins. The changes in various parameters of the hydromineral balance of the animals are consistent with the concept that peptides of the pars intermedia may be involved in regulating plasma aldosterone levels under severe conditions of low plasma sodium concentration.
Selective aromatase inhibition by pyridoglutethimide, an analogue of aminoglutethimide
Authors: Kitawaki Jo , Yamamoto Takara , Urabe Mamoru , Tamura Takaya , Inoue Shigeo , Honjo Hideo , Okada Hiroji
Published: December 2008

The inhibitory effects of pyridoglutethimide (3-ethyl-3-(4-pyridyl)piperidine-2,6-dione), an analogue of aminoglutethimide, on aromatase and other cytochrome P-450-dependent steroid-metabolizing enzymes were studied in vitro. Pyridoglutethimide and aminoglutethimide showed competitive inhibition of human placental aromatase activity with apparent Ki values of 1.7 and 0.7 μmol/l, respectively. Both pyridoglutethimide and aminoglutethimide inhibited the aromatase activity of uterine leiomyoma and cultured choriocarcinoma Enami cells as well as immunopurified human placental aromatase cytochrome P-450 by more than 90%, with IC50 values of 10–19 and 5–7 μmol/l, respectively. These results might suggest that the inhibitors interacted directly with the aromatase cytochrome P-450 of these tissues. Aminoglutethimide inhibited bovine adrenal cholesterol side-chain cleavage activity with an IC50 value of 40 μmol/l and inhibited 21-hydroxylase activity slightly, but did ot inhibit 17α-, 1 1β- and 18-hydroxylase at concentrations up to 100 μmol/l. On the other hand, pyridoglutethimide had no inhibitory effect on any of these enzymes at concentrations up to 50 μmol/l, although it inhibited 11β- and 18-hydroxylase slightly at 100 μmol/l. These results indicated that pyridoglutethimide was an aromatase inhibitor of a comparable potency to aminoglutethimide, but that it did not inhibit other steroid hydroxylases.