bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging
Authors: Ghigo E. , Goffi S. , Arvat E. , Nicolosi M. , Procopio M. , Bellone J. , Imperiale E. , Mazza E. , Baracchi G. , Camanni F. 
Published: June 2009

Abstract.
In 11 elderly normal subjects and in 17 young healthy subjects we studied the response of plasma growth hormone to GH-releasing hormone (GHRH(29), 1 μg/kg iv) alone and preceded by pyridostigmine ( 120 mg orally 60 min before GHRH), a cholinesterase inhibitor likely able to suppress somatostatin release. The GH response to pyridostigmine alone was also examined. Basal plasma GH levels were similar in elderly and young subjects. In the elderly, GHRH induced a GH rise (AUC, median and range: 207.5, 43.5-444.0 μg · 1−1 · h−1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5-2313.5 μg · 1−1 · h−1). The pyridostigmine-induced GH rise in the elderly was similar to that in young subjects (300.5, 163.0-470.0 vs 265.0, 33.0-514.5 μg · 1−1 · h−1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 μg · 1−1 · h−1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 μg · 1−1 · h−1; p = 0.0001 vs GHRH alone). However, the GH response to pyridostigmine + GHRH was significantly lower (p = 0.0001) in elderly than in young subjects. In conclusion, the cholinergic enhancement by pyridostigmine is able to potentiate the blunted GH response to GHRH in elderly subjects, inducing a GH increase similar to that observed after GHRH alone in young adults. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in normal aging. However, a decreased GH response to combined administration of pyridostigmine and GHRH in elderly subjects suggests that other abnormalities may coexist, leading to the secretory hypoactivity of somatotropes.
Physical and psychological capabilities during substitution therapy with recombinant growth hormone in adults with growth hormone deficiency
Authors: Degerblad Marie , Almkvist Ove , Grunditz Roland , Hall Kerstin , Kaijser Lennart , Knutsson Evert , Ringertz Hans , Thorén Marja 
Published: June 2009

Abstract.
In a double-blind cross-over study with recombinant methionyl growth hormone (GH) and placebo during 12 weeks, the effect of GH substitution therapy (0.5-0.6 IU · kg−1 · week−1) on physical performance, muscle strength, bone mineral density, and mood and cognitive functions was investigated in 6 GH-deficient adults. During GH substitution serum concentrations of insulin-like growth factor-I and procollagen-III peptide increased in all 6 patients, whereas concentrations of serum urea decreased. Five of the patients identified the GH period and reported improved well-being with increased mental alertness and vitality and improved physical capacity and muscle strength. There was, however, no change of the isokinetic muscle strength during GH substitution therapy, and the working capacity on the bicycle ergometer was just slightly improved in some patients. The bone mineral density was low and unchanged in all patients. Mood and cognitive functions did not change during GH therapy. A reversible fluid retention was observed in one patient during the GH period. In conclusion, short-term GH substitution therapy to GH-deficient adults induced a subjective improvement of general wellbeing. Longer treatment periods will be necessary to establish the effect on physical capacity, muscle strength, bone mineral density, and mood and cognitive functions.
The mechanism of action of tumour necrosis factor-α and interleukin 1 on FRTL-5 rat thyroid cells
Authors: Pang Xuan-Ping , Hershman Jerome M. , Smith Vierka , Pekary A. Eugene , Sugawara Masahiro 
Published: June 2009

Abstract.
Previous work showed that treatment of rats with tumour necrosis factor-α produced a model of nonthyroid illness in which there was reduction of circulating thyroid hormones and TSH, reduced thyroid response to TSH, and reduced thyroid iodide uptake. In vitro studies showed that tumour necrosis factor-α binds to a specific receptor on FRTL-5 rat thyroid cells, that TSH increases the number of tumour necrosis factor-α receptors, and that tumour necrosis factor-α inhibits iodide uptake by these cells. In the present study, we obtained additional data on the effects of tumour necrosis factor-α on FRTL-5 cells and studied the mechanism of action of tumour necrosis factor-α in these cells. Tumour necrosis factor-α inhibited both basal and TSH-stimulated [125I]iodide uptake; tumour necrosis factor-α slowed the recovery of [125I]iodide trapping after the cells were exposed to TSH and augmented the loss of the [125I]iodide trapping function after the cells were deprived of TSH; tumour necrosis factor-α inhibited [125I]iodide trapping in a noncompetitive manner; tumour necrosis factor-α did not affect cell growth of FRTL-5 cells. Interleukin-1 (IL-1) also inhibited basal and TSH-stimulated [125I]iodide uptake, but it stimulated cell growth. Tumour necrosis factor-α and IL-1 did not affect the generation of cAMP in the presence or absence of TSH; these cytokines blocked the cAMP-induced stimulation of [125I]iodide uptake. Tumour necrosis factor-α did not affect [3H]arachidonic acid uptake or release by FRTL-5 cells. The inhibitors of the phospholipase A2-arachidonic acid pathway did not affect the action of tumour necrosis factor-α. The H2O2 scavenger, catalase, did not block the action of tumour necrosis factor-α. The results show that both tumour necrosis factor-α and IL-1 inhibit FRTL-5 function and that the site of action of these cytokines is distal to the production of cAMP. The actions of tumour necrosis factor-α on FRTL-5 cells do not appear to be mediated by the phospholipase A2-arachidonic acid pathway or by H2O2.
Epidermal growth factor in mice: Effects of estradiol, testosterone and dexamethasone
Authors: Tuomela Tiina , Miettinen Päivi , Pesonen Kristina , Viinikka Lasse , Perheentupa Jaakko 
Published: June 2009

Abstract.
To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kidneys after ovariectomy. After gonadectomy, the male mice had 1.4-fold higher mean epidermal growth factor concentration in the urine than the female, in contrast to a 1.5-fold reverse difference in intact mice; the female mice had 2.5-fold higher concentration in the submandibular glands than the male animals, in contrast to a 4.5-fold reverse difference in intact mice. The kidney sex difference of intact mice (male > female) was abolished. In both gonadectomized sexes, treatment with testosterone increased the concentration of epidermal growth factor in plasma and the submandibular gland; treatment with estradiol increased the concentration in urine and decreased it in the submandibular gland. Treatment with dexamethasone decreased the concentration of epidermal growth factor in plasma of the male mice, and in urine of the female mice, thus decreasing the sex differences. In the submandibular gland and the kidneys, dexamethasone increased the concentration. The mRNA levels were higher in the submandibular gland and lower in the kidneys in the ovariectomized than in the intact female mice. The effects of sex steroids on epidermal growth factor concentrations are mediated through modulation of its gene activity. Testosterone has an increasing and estradiol a decreasing effect in the submandibular gland. Estradiol has also an increasing effect in the kidneys.
Characterization of cytosolic female rat liver receptors of the lactogenic type
Authors: Emtner M. , Roos P. 
Published: June 2009

Abstract.
Some properties of cytosolic receptors of the lactogenic type from female rat liver were studied and compared with those of membrane-bound (microsomal) receptors. The association constant between the cytosolic receptors and human growth hormone was 2.2 l/nmol, which was not significantly different from the value obtained for the microsomal receptors (3.6 l/nmol). Since unlabelled hGH and human prolactin, but not bovine growth hormone, displaced [125I]hGH bound to receptors from both sources, the cytosolic receptors, like the microsomal receptors, must be lactogenic. Furthermore, the cytosolic receptors were recognized by a monoclonal antibody raised against microsomal receptors from female rat liver. However, covalent cross-linking of cytosolic receptors to [125I]hGH and subsequent sodium dodecyl sulphate electrophoresis gave a single band corresponding to a molecular weight of 42 200 (after subtraction of the molecular weight of hGH), which differs significantly (p<0.01) from the values determined for the two distinct bands given by the microsomal fraction. Moreover, upon molecular sieve chromatography the receptor activity in the two fractions appeared at significantly (p<0.05) different elution volumes. These results show that the cytosolic and microsomal receptors have some structural features in common but are definitely not identical.
Inferior petrosal sinus sampling: Evidence of a stimulatory effect of oCRH on GH secretion in Cushing's Disease
Authors: Loli P. , Vignati F. , Scialfa G. , Boccardi E. , Branca V. , Berselli M. E. 
Published: June 2009

Abstract.
Preoperative localization of ACTH-secreting microadenomas has been performed in 9 patients with Cushing's disease by using bilateral and simultaneous venous sampling of the inferior petrosal sinuses. In addition to ACTH and PRL we determined GH levels after oCRH stimulation in order to confirm the possible occurrence of unilateral GH increases, as recently observed by us in one patient. A central-to-peripheral and an intersinus gradient of ACTH concentration was observed in all patients examined before and/or after oCRH stimulation. In 7 patients central-to-peripheral and side-to-side PRL gradients were recorded in basal conditions; in 5 of these patients a unilateral oCRH-induced PRL increase was observed. Six out of the 7 patients with unilateral PRL increases also showed an intersinus GH gradient in basal conditions (ratio ≥ 1.5); in 5 of them a clearcut oCRH-induced GH increase was observed. A peripheral oCRH-induced GH and PRL increase was not observed in any of the patients. The observation of a paradoxical oCRH-induced GH increase in the inferior petrosal sinus with the higher ACTH concentration is of speculative and clinical interest; whether it reflects co-secretion of hormones by the tumour or hormone release by non-tumourous cells via paracrine mechanism is still to be clarified. The unilateral GH increase could represent an additional signal of the presence and localization of an ACTH-secreting tumour.
Binding of insulin-like growth factor-I to rat uterus; variations during sensitization and decidualization
Authors: Chandrasekhar Yallampalli , Narayan Satya , Singh Pomila , Nagamani Manubai 
Published: June 2009

Abstract.
IGF-I receptors have been identified and characterized in a variety of tissues. In this study receptors for IGF-I in the rat uterine tissue were identified and characterized. We have demonstrated IGF-I receptors in crude uterine membranes by binding and cross-linking experiments. IGF-I binding to the rat uterine membranes displayed time, temperature and pH dependance, and optimal binding conditions were achieved by 20 h of incubation at 4°C, at a pH of 7.8. Uterine IGF-I binding sites were specific for binding IGF-I peptide and demonstrated less than 100 × lower affinity for insulin. The binding was reversible and Scatchard analysis indicated presence of a single class of binding sites with an apparent dissociation constant of 1.68 ± 0.24 nmol/l and Bmax of 0.82 ± 0.1 pmol/mg protein. During estrogen treatment, sensitization and decidualization there was an overall increase of membrane proteins in the uterus and a relative decrease of IGF-I receptors per unit of protein. When expressed on a per uterus basis, there was a progressive increment in total IGF-I binding in estradiol-treated, sensitized, and decidualized uterus compared with controls. These data indicate a possible role for IGF-I in uterine cell multiplication and further differentiation to decidual cells in response to deciduogenic stimuli.
Calcitonin causes a sustained inhibition of protein kinase C-stimulated bone resorption in contrast to the transient inhibition of parathyroid hormone-induced bone resorption
Authors: Ransjö Maria , Lerner Ulf H. 
Published: June 2009

Abstract.
Calcitonin is a well known inhibitor of osteoclastic bone resorption, both in vivo and in vitro. However, it is also known that calcitonin has only a transient inhibitory effect on bone resorption. The mechanism for this so-called "escape from inhibition" phenomenon is not clear. In the present study, the inhibitory effect of calcitonin on phorbol ester-induced bone resorption was examined in cultured neonatal mouse calvaria. Bone resorption was assessed as the release of radioactivity from bones prelabelled in vivo with 45Ca. Two protein kinase C-activating phorbol esters, phorbol-12-myristate-13-acetate and phorbol-12,13-dibutyrate, both stimulated 45Ca release in 120-h cultures at a concentration of 10 nmol/l. Calcitonin (30 nmol/l) inhibited phorbol esterstimulated bone resorption without any "escape from inhibition". This was in contrast to the transient inhibitory effect of calcitonin on bone resorption stimulated by parathyroid hormone (10 nmol/l), prostaglandin E2 (2 μmol/l), and bradykinin (1 μmol/l). Our results suggest that activation of protein kinase C produces a sustained inhibitory effect of calcitonin on bone resorption.
Circadian patterns of serum insulin-like growth factor (IGF) II and IGF binding protein 3 in growth hormone-deficient patients and age- and sex-matched normal subjects
Authors: Jørgensen Jens Otto L. , Blum Werner F. , Møller Niels , Ranke Michael B. , Christiansen Jens S. 
Published: June 2009

Abstract.
Knowledge of the circadian patterns of serum IGF-I I and the large molecular weight IGF binding protein, IGFBP-3 might, apart from its physiological relevance, be of clinical interest, inasmuch as measurements of these parameters are being introduced into the evaluation of GH deficiency. We therefore evaluated the 24-h (08.00-08.00 h) patterns of serum IGF-II and IGFBP-3 in 8 GH-deficient patients who were studied during three periods when receiving 1. GH (2 IU) at 20.00 h; 2. GH (2 IU) at 08.00 h and 3. no GH. For comparison, 10 age- and sex-matched untreated healthy subjects were studied once under similar conditions. The serum IGF-II levels of the patients were relatively stable over the 24-h periods, yielding mean levels which were significantly lower during no GH: 553±78 (evening GH), 554±54 (morning GH), and 429±65 μg/l (no GH). The mean IGF-II level in the normal subjects was 635±29 μg/l, which was significantly higher than in either patient study. Similarly, stable 24-h levels of IGFBP-3 were recorded in all studies. The mean IGFBP-3 level of the patients was significantly lower when they received no GH, and the mean level in the healthy subjects was higher than in any of the patient studies: 1853±301 (no GH), 2755 ± 317 (evening GH), 2904±269 (morning GH), and 3856±186 μg/l (healthy subjects). However, minute but significant changes over time, characterised by slight decrements at night, were observed for both parameters in several of the studies. Nevertheless, since both IGF-II and IGFBP-3 display rather stable 24-h levels in the individual, it is concluded that measurements of these parameters in evaluation of growth retardation can be based on a single daytime sample.
Androgen receptor disorder in three brothers with bifid prepenile scrotum and hypospadias
Authors: Bals-Pratsch Monika , Schweikert Hans-Udo , Nieschlag Eberhard 
Published: June 2009

Abstract
Three brothers with congenital transposition of the penis, scrotal hypospadias, bifid scrotum, and bilateral undescended testes are described. Further signs of incomplete virilization, but no gynecomastia were seen. LH and FSH were elevated, whereas testosterone levels were reduced or in the normal range. Serum concentrations of 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 5α-dihydrotestosterone and estradiol measured in two affected brothers were in the normal range. Fibroblasts from scrotal skin biopsies performed in two patients showed normal 5α-reductase activity (419 and 214 pmol · (mg protein)−1 · h−1; normal >1), whereas androgen receptors had reduced maximal binding capacity (Bmax 4 and 14 fmol · (mg protein)−1; normal ≥ 18) and an increased equilibrium dissociation constant (0.7 and 1.26 nmol/l; normal 0.2±0.08) indicating a quantitative and qualitative androgen receptor defect. These patients represent a further variant of androgen insensitivity.
Thyroid-stimulating activity of human chorionic gonadotropin in sera of normal pregnant women
Authors: Yoshimura Masayoshi , Nishikawa Mitsushige , Horimoto Masateru , Yoshikawa Norio , Sawaragi Susumu , Horikoshi Yorihiko , Sawaragi Isamu , Inada Mitsuo 
Published: June 2009

Abstract.
To ascertain the thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the adenylate cyclase activation in the cultured FRTL-5 cells by extracted hCG from 7 normal pregnant women. hCG was extracted from the sera using anti-hCG-β subunit monoclonal antibodycoated microwells, eluted with 2 mol/l guanidine-HCl, and reconstituted with hypotonic Hanks' solution. FRTL-5 cells were precultured in 5H medium, incubated for 2 h with the serum extracts, and the cAMP released into the medium was measured. hCG levels in serum extracts ranged from 1100 to 6800 IU/l; values corresponded to 1.4-19.8% compared with those in the original serum samples. Addition of the extracts to FRTL-5 cells resulted in significant increases in the cAMP accumulation, ranging from 9.8 to 59.0 nmol/l. cAMP levels were also increased in a dose-dependent manner by adding purified hCG as well as crude hCG and hTSH to FRTL-5 cells. These findings suggest that the thyroid gland of normal pregnant women may actually be stimulated by hCG itself.
Pharmacokinetics of the antiprogesterone RU 486: No correlation to clinical performance of RU 486
Authors: Heikinheimo Oskari , Ylikorkala Olavi , Turpeinen Ursula , Lähteenmäki Pekka 
Published: June 2009

Abstract.
The pharmacokinetics and metabolism of RU 486 were characterized in 17 women who received a single dose of 600 mg of RU 486 for termination of an early unwanted pregnancy. Based on the clinical outcome and serum chorionic gonadotropin values, the subjects were divided into two groups: those who aborted completely (i.e. responders; N=13) and those who did not respond to RU 486 treatment (i.e. non-responders; N = 4). The serum levels of RU 486, the monodemethylated, didemethylated and hydroxylated metabolites of RU 486 were measured by HPLC preceded by column chromatography. There were no significant differences in the serum levels of RU 486 or its metabolites between the two groups. The serum concentrations of α1-acid glycoprotein, the binding protein for RU 486, were quantitated by immunoturbidimetry. The α1-acid glycoprotein concentrations were similar in responders and non-responders. The metabolism of RU 486 was also studied by fractionating extracts of serum pools of responders and nonresponders on thin-layer chromatography, and subsequent RIA analysis of the eluates of the sliced thin-layer chromatography. Spots with similar distribution and percentages of cross-reactivity were found in both groups on the chromatography; the results were also similar to those from a serum pool to which synthetic RU 486 and its three metabolites had been added. Hence it is concluded that failure to abort in response to RU 486 therapy is not associated with altered pharmacokinetics or metabolism of RU 486.
A longitudinal study of total and free thyroid hormones and thyroxinebinding globulin during normal puberty
Authors: Dunger David B. , Perkins Janet A. , Jowett Terence P. , Edwards Philip R. , Cox Leslie A. , Preece Michael A. , Ekins Roger P. 
Published: June 2009

Abstract.
Thyroid hormones are essential for normal pubertal growth, yet the changes in total and, especially, free thyroid hormones and thyroxine-binding globulin during puberty have not been adequately defined. Serum from 39 normal children (20 girls, 19 boys) between the ages of 10 and 15 years were assayed for total T4, free T4, free T3 and thyroxine-binding globulin at 6-monthly intervals; the free hormone assays were valid, non-analogue methodologies. In the girls, free T4 levels fell from 15.7±0.6 pmol/l at 10 years to 13.0±0.6 (p<0.001) at 12.5 years before rising to 15.9±0.7 at 15 years; this nadir occurred at puberty stages 3-4. Changes in total T4 followed a similar pattern with a slight delay in the nadir (13 years, puberty stage 4). In the boys, free T4 fell from 16.3±0.6 pmol/l at 10 years to 14.3±0.3 at 13.5 years, then rising to 15.4±0.5 at 15 years; the nadir again occurred at puberty stages 3-4. The corresponding nadir in total T4 which occurred at puberty stages 4-5 was not apparent by age analysis. Thyroxine-binding globulin concentrations remained unchanged in the girls, but fell slightly in the boys during later puberty. Free T3 concentrations in the girls showed a progressive fall after 12.5 years which was significant by the age of 14 when most had been in puberty stage 5 for more than 1 year. The boys showed no change of free T3 concentration throughout the study. These data demonstrate important differences in the levels of free thyroid hormones in males and females during puberty. Normal ranges for girls and boys between the ages of 9.5 and 15.5 years are presented.
Antithyroid drug treatment of Graves' disease in pregnancy: Long-term effects on somatic growth, intellectual development and thyroid function of the offspring
Authors: Messer Peter M. , Hauffa Berthold P. , Olbricht Thomas , Benker Georg , Kotulla Peter , Reinwein Dankwart 
Published: June 2009

Abstract.
With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N=12) and propylthiouracil (N=1). Age at examination in group I was 7.2±6.2 years, in group II 8.7±7.1 years (mean±sd). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II(3165±339 vs 3666±670 g, p<0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 ± 2.4 vs 14.9±1.9 pmol/l, p<0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period.