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Sample records for human thyroid-stimulating hormone

  1. First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

    NARCIS (Netherlands)

    Pratt, JJ; de Wolf, BTHM; Mantingh, A

    2001-01-01

    Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

  2. Rabbits immunized with thyroid-stimulating hormone produce autoantiidiotypic thyroid-stimulating antibodies.

    OpenAIRE

    Beall, G N; Rapoport, B; Chopra, I J; Kruger, S R

    1985-01-01

    We immunized rabbits with thyroid-stimulating hormone (TSH) to investigate the hypothesis that such immunization could result in production of thyroid-stimulating autoantiidiotypic antibodies to anti-TSH. Thyroid-stimulating immunoglobulin (TSI) appeared in the serum of several rabbits after immunization. At 160 d, TSI equivalent to 6-18 microU TSH/1.5 mg IgG was present in two of six human (h)TSH-, two of six hTSH beta chain-, and two of the four surviving bovine (b)TSH-immunized animals. Co...

  3. Site-specific PEGylation of human thyroid stimulating hormone to prolong duration of action.

    Science.gov (United States)

    Qiu, Huawei; Boudanova, Ekaterina; Park, Anna; Bird, Julie J; Honey, Denise M; Zarazinski, Christine; Greene, Ben; Kingsbury, Jonathan S; Boucher, Susan; Pollock, Julie; McPherson, John M; Pan, Clark Q

    2013-03-20

    Recombinant human thyroid stimulating hormone (rhTSH or Thyrogen) has been approved for thyroid cancer diagnostics and treatment under a multidose regimen due to its short circulating half-life. To reduce dosing frequency, PEGylation strategies were explored to increase the duration of action of rhTSH. Lysine and N-terminal PEGylation resulted in heterogeneous product profiles with 40% or lower reaction yields of monoPEGylated products. Eleven cysteine mutants were designed based on a structure model of the TSH-TSH receptor (TSHR) complex to create unique conjugation sites on both α and β subunits for site-specific conjugation. Sequential screening of mutant expression level, oligomerization tendency, and conjugation efficiency resulted in the identification of the αG22C rhTSH mutant for stable expression and scale-up PEGylation. The introduced cysteine in the αG22C rhTSH mutant was partially blocked when isolated from conditioned media and could only be effectively PEGylated after mild reduction with cysteine. This produced a higher reaction yield, ~85%, for the monoPEGylated product. Although the mutation had no effect on receptor binding, PEGylation of αG22C rhTSH led to a PEG size-dependent decrease in receptor binding. Nevertheless, the 40 kDa PEG αG22C rhTSH showed a prolonged duration of action compared to rhTSH in a rat pharmacodynamics model. Reverse-phase HPLC and N-terminal sequencing experiments confirmed site-specific modification at the engineered Cys 22 position on the α-subunit. This work is another demonstration of successful PEGylation of a cysteine-knot protein by an engineered cysteine mutation.

  4. Rabbits immunized with thyroid-stimulating hormone produce autoantiidiotypic thyroid-stimulating antibodies.

    Science.gov (United States)

    Beall, G N; Rapoport, B; Chopra, I J; Kruger, S R

    1985-05-01

    We immunized rabbits with thyroid-stimulating hormone (TSH) to investigate the hypothesis that such immunization could result in production of thyroid-stimulating autoantiidiotypic antibodies to anti-TSH. Thyroid-stimulating immunoglobulin (TSI) appeared in the serum of several rabbits after immunization. At 160 d, TSI equivalent to 6-18 microU TSH/1.5 mg IgG was present in two of six human (h)TSH-, two of six hTSH beta chain-, and two of the four surviving bovine (b)TSH-immunized animals. Control (human serum albumin-immunized rabbits) serum TSI was 4.3 +/- 0.4 (mean +/- SD) at this time. Antiidiotypic antibodies that could bind to monoclonal anti-hTSH were found in the sera of the bTSH-immunized rabbits. The peak TSI activity occurred 3 mo after a TSH booster immunization and declined gradually during subsequent weeks. Evidence that antiidiotypic antibodies to anti-TSH can cause thyroid stimulation strengthens the notion that such antibodies may be the cause of Graves' hyperthyroidism.

  5. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    DEFF Research Database (Denmark)

    Jansen, S W; Akintola, A A; Roelfsema, F;

    2015-01-01

    hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... may favour longevity without altering energy metabolism....

  6. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)

    2007-12-15

    Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

  7. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Directory of Open Access Journals (Sweden)

    G.J. Paz-Filho

    2007-12-01

    Full Text Available Recombinant human thyroid-stimulating hormone (rhTSH enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG. Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years, who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4% (P < 0.001, a median 2.6-fold increase (1.2 to 9.2. Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase, 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%, painful thyroiditis (29.4% and hypothyroidism (52.9%. Thyroid volume was reduced by 34.3 ± 14.3% after 6 months (P < 0.001 and by 46.0 ± 14.6% after 1 year (P < 0.001. Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

  8. A Novel Combination of Immunoreaction and ICP-MS as a Hyphenated Technique for the Determination of Thyroid-stimulating Hormone (TSH) in Human Serum

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The novel coupling method based on the hyphenation of immunoreaction with ICP-MS is developed and applied to the determination of thyroid-stimulating hormone (TSH) in human serum. In this system, TSH is firstly captured by anti-TSH monoclonal antibodies immobilized on a solid support. Biotinylated anti-TSH monoclonal antibodies and Eu3+-labelled streptavidin are then added to form the complex capturing andbody-TSH-biotinylated anti-TSH antibody-Eu3+-labeled streptavidin. After unbound reactants are washed away, Eu3+ bound to the complex is extracted by

  9. Thyroid ultrasonography in congenital isolated thyroid stimulating hormone deficiency.

    OpenAIRE

    Wakamoto, H; Miyazaki, M.; Tatsumi, K; Amino, N

    1995-01-01

    The effects of thyroid stimulating hormone (TSH) deficiency on thyroid development was examined using ultrasonography in a child with congenital isolated TSH deficiency. Ultrasound revealed the thyroid gland was one sixth normal volume, suggesting that TSH plays an important part in thyroid growth, but not a critical role in differentiation.

  10. Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective

    Directory of Open Access Journals (Sweden)

    Seo Young Sohn

    2015-12-01

    Full Text Available BackgroundPrevious studies have suggested that recombinant human thyroid stimulating hormone (rhTSH stimulation is an acceptable alternative to thyroid hormone withdrawal (THW when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective.MethodsThis economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets.ResultsThe additional benefits of rhTSH (0.036 QALY are achieved with an additional cost of Korean won ₩961,105, equating to cost per QALY of ₩26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately ₩33,000,000/QALY.ConclusionThe use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea.

  11. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-06-15

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  12. Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals.

    Science.gov (United States)

    Vallejo, J A; Muros, M A

    2017-05-20

    In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  13. Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), are located less than 310 kb apart in both human and mouse genomes.

    Science.gov (United States)

    Dracopoli, N C; Rose, E; Whitfield, G K; Guidon, P T; Bale, S J; Chance, P A; Kourides, I A; Housman, D E

    1988-08-01

    Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), have been assigned to mouse chromosome 3 and human chromosome 1p22. We have used the techniques of linkage analysis and pulsed field gel electrophoresis to determine the proximity of these two antithetically regulated genes in this conserved linkage group. Four novel restriction fragment length polymorphisms were identified at the human TSHB gene. Two-point linkage analysis between TSHB and NGFB in 46 families, including the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel, demonstrated no recombination (theta = 0.00, Z = 42.8). Analysis of this region by pulsed field gel electrophoresis showed that the genes for TSHB and NGFB are located less than 310 kb apart in man and 220 kb in the mouse.

  14. Application of europium(III) chelates-bonded silica nanoparticle in time-resolved immunofluorometric detection assay for human thyroid stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yulin [Xiamen Branch of Fujian Newborn Screening Centre and Xiamen Prenatal Diagnosis Centre, Xiamen Maternal and Children' s Health Care Hospital, Xiamen, Fujian 361003 (China); Xia Xiaohu; Xu Ye; Ke Wei [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Yang Wei, E-mail: weiyang@xmu.edu.cn [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Li Qingge, E-mail: qgli@xmu.edu.cn [Engineering Research Centre of Molecular Diagnostics Laboratory, MOE, Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer A rapid and ultrasensitive TSH immunoassay was developed using fluorescent silica nanoparticles-based TrIFA. Black-Right-Pointing-Pointer The assay is of high sensitivity with short period time request. Black-Right-Pointing-Pointer method can be potentially used at hospitals for daily clinical practice in hTSH screening. - Abstract: Eu(III) chelate-bonded silica nanoparticle was used as a fluorescent label to develop a highly sensitive time-resolved immunofluorometric assay (TrIFA) for human thyroid stimulating hormone (hTSH). The limit of detection of the assay calculated according to the 2SD method was 0.0007 mIU L{sup -1} and became 0.003 mIU L{sup -1} when serum-based matrix was used for calibrators, indicating that this TrIFA is comparable with the most sensitive assays. The linear range was from 0.005 to 100 mIU L{sup -1} of hTSH with coefficient of variation between 1.9% and 8.3%. The correlation study using 204 blood spot samples from newborns showed that the results from this new method were coincident with that of the commercial dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) system, with a correlation coefficient of 0.938. The fluorescent nanoparticle label allows directly reading the fluorescent signal, omitting the signal development step required for the DELFIA system, and the whole procedure of this assay is fulfilled within 2 h. Thus, we developed a novel, sensitive, quantitative and simple nanoparticle label-based TrIFA assay, suitable for routine application in hTSH screening of neonatal hypothyroidism.

  15. Analysis of clinical factors for the determination of optimal serum level of thyrotropin after recombinant human thyroid-stimulating hormone administration

    Energy Technology Data Exchange (ETDEWEB)

    Son, Seung Hyun; Lee, Sang Woo; Jung, Ji Hoon; Kim, Choon Young; Kim, Do Hoon; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae [Dept. of Nuclear Medicine, Kyungpook National University Medical Center and School of Medicine, Daegu (Korea, Republic of)

    2015-12-15

    To determine the optimal levels of thyroid-stimulating hormone (TSH) levels after administration of recombinant human TSH (rhTSH) to patients with differentiated thyroid cancer (DTC), we have analyzed the clinical parameters that affected the degree of the increase in serum levels of TSH. We retrospectively analyzed 276 patients with differentiated thyroid cancer (DTC), post-thyroidectomy and remnant ablation. Pearson’s correlation coefficient test was used to evaluate the correlation between serum levels of TSH after rhTSH stimulation and various clinical factors, including age, sex, height, weight, body mass index (BMI), body surface area (BSA), serum blood urea nitrogen, creatinine, and estimated glomerular filtration rate (GFR). Linear regression analysis was used to determine the predictors of the degree of increase in serum TSH level after rhTSH stimulation. After the rhTSH injections, all subjects achieved TSH levels of >30 μU/mL, with a mean of 203.8 ± 83.4 μU/mL. On univariate analysis, age (r = 0.255) and serum creatinine (r = 0.169) level were positive predictors for higher levels of serum TSH after rhTSH stimulation, while weight (r = –0.239), BMI (r = –0.223), BSA (r = –0.217), and estimated GFR (r = –0.199) were negative predictors. Multiple linear regression analysis revealed that serum creatinine was the most powerful independent predictor for serum levels of TSH, followed by age, BSA, and BMI. An increment in serum TSH after rhTSH stimulation was significantly affected by age, BSA, BMI, and creatinine, with creatinine being the most powerful predictor. By understanding the difference in the increased levels of TSH in various subjects, their dose of rhTSH can be adjusted during scheduling for radioiodine ablation, or during follow-up (recurrence surveillance) after surgery and ablation.

  16. Thyroid stimulating hormone and cognition during severe, transient hypothyroidism.

    Science.gov (United States)

    Schraml, Frank V; Goslar, Pamela W; Baxter, Leslie; Beason-Held, Lori L

    2011-01-01

    The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of 'brain hypothyroidism' such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis. Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients' neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid. The patients' performance while hypothyroid was worse than that of the controls in only one neurocognitive measure--Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure - Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients' performance on these same two measures, but no others. Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests that serum TSH level may reflect the severity of 'brain hypothyroidism' during the overt stage of this condition.

  17. Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, S.; Tanaka, K.; Kumagae, M.; Takeda, F.; Morio, K.; Kogure, M.; Hasegawa, M.; Horiuchi, T.; Watabe, T.; Miyabe, S.

    1988-01-01

    SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 ..mu..g of SMS or a placebo to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50, and 100 ..mu..g of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50, and 100 ..mu..g of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values.

  18. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ines Bucci

    2017-06-01

    Full Text Available Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH receptor (TSHR antibodies (TRAbs are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs, blocking (TBAbs, or neutral (N-TRAbs depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and

  19. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

    Science.gov (United States)

    Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

    2015-01-01

    Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

  20. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

    Science.gov (United States)

    Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

    2015-01-01

    Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

  1. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease

    DEFF Research Database (Denmark)

    Brand, Oliver J; Barrett, Jeffrey C; Simmonds, Matthew J;

    2009-01-01

    Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating...... hormone, causing the characteristic clinical phenotype. Although early studies investigating the TSHR and GD proved inconclusive, more recently we provided convincing evidence for association of the TSHR region with disease. In the current study, we investigated a combined panel of 98 SNPs, including 70...

  2. Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS.

    Science.gov (United States)

    Dittrich, Ralf; Kajaia, Natia; Cupisti, Susanne; Hoffmann, Inge; Beckmann, Matthias W; Mueller, Andreas

    2009-09-01

    There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic parameters. Little information is available regarding this relationship in women with polycystic ovary syndrome. However all those pathologies are also described as often affecting women with polycystic ovary syndrome. The association between thyroid-stimulating hormone or =2.5 mIU/l with insulin resistance and endocrine parameters in 103 women with polycystic ovary syndrome was studied. Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed with calculation of insulin resistance indices. Women with thyroid-stimulating hormone > or =2.5 mIU/l had a significantly higher body mass index (P = 0.003), higher fasting insulin concentrations (P = 0.02) and altered insulin resistance indices (P = 0.007), higher total testosterone (P = 0.009) and free androgen indices (P = 0.001) and decreased sex hormone-binding globulin concentrations (P = 0.01) in comparison with women with thyroid-stimulating hormone or =2.5 mIU/l. Women with polycystic ovary syndrome and with thyroid-stimulating hormone > or =2.5 mIU/l had significantly altered endocrine and metabolic changes.

  3. Thyroid peroxidase antibodies, levels of thyroid stimulating hormone and development of hypothyroidism in euthyroid subjects

    NARCIS (Netherlands)

    Roos, A.; Links, T.P.; de Jong-van den Berg, L.T.; Gans, R.O.; Wolffenbuttel, B.H.; Bakker, S.J.

    2010-01-01

    Objective: Thyroid peroxidase antibodies (TPOAbs) have been found to be related to the levels of thyroid stimulating hormone (TSH) and to predict future development of thyroid failure in selected populations. We investigated these relations in a euthyroid general population. Design: Cross-sectional

  4. Thyroid-stimulating Hormone (TSH): Measurement of Intracellular, Secreted, and Circulating Hormone in Xenopus laevis and Xenopus tropicalis.

    Science.gov (United States)

    Thyroid Stimulating Hormone (TSH) is a hormone produced in the pituitary that stimulates the thyroid gland to grow and produce thyroid hormone (TH). The concentration of TH controls developmental changes that take place in a wide variety of organisms. Many use the metaphoric ch...

  5. Expression of thyroid stimulating hormone β splice variant in thyroid of mouse with autoimmune thyroiditis

    Institute of Scientific and Technical Information of China (English)

    袁继红

    2014-01-01

    Objective To investigate the expression of marrowderived thyroid stimulating hormoneβ(TSHβ)splice variant in thyroid of mouse with autoimmune thyroiditis induced by thyroglobulin(Tg)immunization,and to analyze whether TSHβsplice variant participated in the pathological process of autoimmune thyroiditis.Methods Using random number table,forty-eight mice(24 females and 24 males)of 7 to 8 weeks old with body mass 20 to25 g were randomly divided into 4 groups(12 females

  6. Serum thyroid stimulating hormone (TSH) in malnutrition: preliminary results.

    Science.gov (United States)

    Osman, A; Khalid, B A; Tan, T T; Wan Nazaimoon, W M; Wu, L L; Ng, M L

    1993-06-01

    This is a report of a cross sectional study involving 3 groups of children, moderately malnourished (BMI BMI 15-18) and well nourished (BMI > 18) to determine the differences in hormonal and biochemical parameters between the groups. The children were of age range from 7-17 years old. The children were from the same area with exposure to the same food, drinking water and environment. There were significant differences in the nutritional indices between the three groups. No differences were observed in levels of triiodothyronine (T3), thyroxine (T4) and T3:T4 ratio. Significant difference however was found in the TSH levels using highly sensitive IRMA TSH assays. Moderately malnourished children had higher TSH levels (p < 0.05) compared to mildly malnourished and well-nourished children. No difference was found between the mildly malnourished and well-nourished groups. There were no significant differences in serum cortisols done at similar times, fasting growth hormone and calcium. Serum alanine transminase (ALT) however was higher in moderately malnourished than in well-nourished children. Thus using highly sensitive IRMA TSH assays, we were able to detect differences in TSH levels even though T3, T4 and T3:T4 ratio, cortisol, growth hormone and calcium were normal, implying in moderately malnourished children, a higher TSH drive to maintain euthyroid state.

  7. Expression of thyroid stimulating hormone receptor in differentiated thyroid carcinoma and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    李清怀

    2013-01-01

    Objective To explore the expression of thyroid stimulating hormone (TSH) receptor in differentiated thyroid carcinoma and its clinical significance.Methods Seventy-four patients with differentiated thyroid carcinoma treated in our department from January 2009 to January 2011were selected as the observation group,and 28 patients with nodular goiter were selected as the control group.Expression of TSH receptor in the two groups were detected by immunohistochemistry.Results The positive rate of TSH receptor expression in the observation group was55.4 (41/74) ,significantly lower than that of the control

  8. De novo triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

    Science.gov (United States)

    Citterio, Cintia E; Veluswamy, Balaji; Morgan, Sarah J; Galton, Valerie A; Banga, J Paul; Atkins, Stephen; Morishita, Yoshiaki; Neumann, Susanne; Latif, Rauf; Gershengorn, Marvin C; Smith, Terry J; Arvan, Peter

    2017-09-15

    The thyroid gland secretes primarily tetraiodothyronine (T4), and some triiodothyronine (T3). Under normal physiological circumstances, only one-fifth of circulating T3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T3 toxicosis. Thyroidal T4 production results from iodination of thyroglobulin (TG) at residues Tyr(5) and Tyr(130), whereas thyroidal T3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T3 is formed de novo independently of deiodination from T4 We found that upon iodination in vitro, de novo T3 formation in TG was decreased in mice lacking TSHRs. Conversely, de novo T3 that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced de novo T3 formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T3 Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances de novo T3 formation, contributing to the relative T3 toxicosis of Graves' disease.

  9. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease.

    Science.gov (United States)

    Brand, Oliver J; Barrett, Jeffrey C; Simmonds, Matthew J; Newby, Paul R; McCabe, Christopher J; Bruce, Christopher K; Kysela, Boris; Carr-Smith, Jackie D; Brix, Thomas; Hunt, Penny J; Wiersinga, Wilmar M; Hegedüs, Laszlo; Connell, John; Wass, John A H; Franklyn, Jayne A; Weetman, Anthony P; Heward, Joanne M; Gough, Stephen C L

    2009-05-01

    Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating hormone, causing the characteristic clinical phenotype. Although early studies investigating the TSHR and GD proved inconclusive, more recently we provided convincing evidence for association of the TSHR region with disease. In the current study, we investigated a combined panel of 98 SNPs, including 70 tag SNPs, across an extended 800 kb region of the TSHR to refine association in a cohort of 768 GD subjects and 768 matched controls. In total, 28 SNPs revealed association with GD (P associations at rs179247 (chi(2) = 32.45, P = 8.90 x 10(-8), OR = 1.53, 95% CI = 1.32-1.78) and rs12101255 (chi(2) = 30.91, P = 1.95 x 10(-7), OR = 1.55, 95% CI = 1.33-1.81), both located in intron 1 of the TSHR. Association of the most associated SNP, rs179247, was replicated in 303 GD families (P = 7.8 x 10(-4)). In addition, we provide preliminary evidence that the disease-associated genotypes of rs179247 (AA) and rs12101255 (TT) show reduced mRNA expression ratios of flTSHR relative to two alternate TSHR mRNA splice variants.

  10. Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies

    Science.gov (United States)

    Davies, Terry F; Latif, Rauf

    2015-01-01

    Introduction The thyroid-stimulating hormone receptor (TSHR) is the essential molecule for thyroid growth and thyroid hormone production. Since it is also a key autoantigen in Graves’ disease and is involved in thyroid cancer pathophysiology, the targeting of the TSHR offers a logical model for disease control. Areas covered We review the structure and function of the TSHR and the progress in both small molecule ligands and TSHR antibodies for their therapeutic potential. Expert opinion Stabilization of a preferential conformation for the TSHR by allosteric ligands and TSHR antibodies with selective modulation of the signaling pathways is now possible. These tools may be the next generation of therapeutics for controlling the pathophysiological consequences mediated by the effects of the TSHR in the thyroid and other extrathyroidal tissues. PMID:25768836

  11. Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

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    Kunii Yasuto

    2011-09-01

    Full Text Available Abstract Introduction Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus. Case presentation Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus. Conclusions In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.

  12. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone.

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    Patanè, Salvatore; Marte, Filippo; Di Bella, Gianluca; Cerrito, Marco; Coglitore, Sebastiano

    2009-05-01

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs significantly increase mean arterial blood pressure compared with controls and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. It has also been reported that sub-clinical hypothyroidism is associated with a significant risk of coronary heart disease (CHD). We present a case of arterial hypertensive crisis and acute myocardial infarction in a 59-year-old Italian man with high levels of thyroid stimulating hormone and with an abundant ingestion of peppers and of chili peppers which occurred the day before.

  13. Impact of light exposure on thyroid-stimulating hormone results using the Siemens Advia Centaur TSH-3Ultra assay.

    Science.gov (United States)

    Armer, Jane; Giles, Diane; Lancaster, Ian; Brownbill, Kathryn

    2017-09-01

    Background Thyroid-stimulating hormone (TSH) is used as the first-line test of thyroid function. Siemens Healthcare Diagnostics recommend that Siemens Centaur reagents must be protected from light in the assay information and on reagent packaging. We have compared the effect of light exposure on results using Siemens TSH-3Ultra and follicle-stimulating hormone reagents. The thyroid-stimulating hormone reagent includes fluoroscein thiocyanate whereas the follicle-stimulating hormone reagent does not. Methods Three levels of quality controls were analysed using SiemensTSH-3Ultra and follicle-stimulating hormone reagent packs that had been kept protected from light or exposed to light at 6-h intervals for 48 h and then at 96 h. Results Thyroid-stimulating hormone results were significantly lower after exposure of TSH-3Ultra reagent packs to light. Results were >15% lower at all three levels of quality control following 18 h of light exposure and continued to decrease until 96 h. There was no significant difference in follicle-stimulating hormone results whether reagents had been exposed to or protected from light. Conclusions Thyroid-stimulating hormone results but not follicle-stimulating hormone results are lowered after exposure of reagent packs to light. Laboratories must ensure that TSH-3Ultra reagents are not exposed to light and analyse quality control samples on every reagent pack to check that there has not been light exposure prior to delivery. The labelling on TSH-3Ultra reagent packs should reflect the significant effect of light exposure compared with the follicle-stimulating hormone reagent. We propose that the effect of light exposure on binding of fluoroscein thiocyanate to the solid phase antibody causes the falsely low results.

  14. Receptors for thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormones in the macaque uterus: effects of long-term sex hormone treatment.

    Science.gov (United States)

    Hulchiy, Mariana; Zhang, Hua; Cline, J Mark; Hirschberg, Angelica Lindén; Sahlin, Lena

    2012-11-01

    Thyroid gland dysfunction is associated with menstrual cycle disturbances, infertility, and increased risk of miscarriage, but the mechanisms are poorly understood. However, little is known about the regulation of these receptors in the uterus. The aim of this study was to determine the effects of long-term treatment with steroid hormones on the expression, distribution, and regulation of the receptors for thyrotropin-releasing hormone (TRHR) and thyroid-stimulating hormone (TSHR), thyroid hormone receptor α1/α2 (THRα1/α2), and THRβ1 in the uterus of surgically menopausal monkeys. Eighty-eight cynomolgus macaques were ovariectomized and treated orally with conjugated equine estrogens (CEE; n = 20), a combination of CEE and medroxyprogesterone acetate (MPA; n = 20), or tibolone (n = 28) for 2 years. The control group (OvxC; n = 20) received no treatment. Immunohistochemistry was used to evaluate the protein expression and distribution of the receptors in luminal epithelium, glands, stroma, and myometrium of the uterus. Immunostaining of TRHR, TSHR, and THRs was detected in all uterine compartments. Epithelial immunostaining of TRHR was down-regulated in the CEE + MPA group, whereas in stroma, both TRHR and TSHR were increased by CEE + MPA treatment as compared with OvxC. TRHR immunoreactivity was up-regulated, but THRα and THRβ were down-regulated, in the myometrium of the CEE and CEE + MPA groups. The thyroid-stimulating hormone level was higher in the CEE and tibolone groups as compared with OvxC, but the level of free thyroxin did not differ between groups. All receptors involved in thyroid hormone function are expressed in monkey uterus, and they are all regulated by long-term steroid hormone treatment. These findings suggest that there is a possibility of direct actions of thyroid hormones, thyroid-stimulating hormone and thyrotropin-releasing hormone on uterine function.

  15. Impact of elevated thyroid-stimulating hormone levels in polycystic ovary syndrome.

    Science.gov (United States)

    Trummer, Christian; Schwetz, Verena; Giuliani, Albrecht; Obermayer-Pietsch, Barbara; Lerchbaum, Elisabeth

    2015-10-01

    The objective of this study was to analyse the impact of elevated thyroid-stimulating hormone (TSH) levels on the metabolic and endocrine phenotype in 583 women with polycystic ovary syndrome (PCOS). Endocrine and metabolic parameters were measured in all patients and compared between women with and without elevated TSH levels. Of the 583 women with PCOS, 125 women (21.4%) had thyroid disturbances (thyroid replacement therapy: 109 women, subclinical hypothyroidism: 16 women). Patients with elevated TSH levels had significantly increased fasting insulin, area under the curve-insulin, homeostatic model assessment-insulin resistance, and total cholesterol (TC)/high-density lipoprotein cholesterol (HDL) ratio and lower free thyroxin, insulin sensitivity and HDL (p < 0.05 for all). Euthyroid PCOS women with thyroid hormone substitution showed significant differences in TSH, age, body mass index, HDL and systolic blood pressure compared to those without hormone replacement therapy (p < 0.05 for all). We conclude that hypothyroid disturbances and elevated TSH levels are common findings in PCOS, which are associated with an adverse metabolic profile. Therefore, women with diagnosed PCOS should be screened for thyroid dysfunction.

  16. A clinical and therapeutic approach to thyrotoxicosis with thyroid-stimulating hormone suppression only.

    Science.gov (United States)

    Papi, Giampaolo; Papi, Giovanni; Pearce, Elizabeth N; Braverman, Lewis E; Betterle, Corrado; Roti, Elio

    2005-04-01

    Subclinical hyperthyroidism is defined as normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations and persistently suppressed thyroid stimulating hormone (TSH) concentrations. The most common cause of subclinical hyperthyroidism is the use of suppressive doses of L-thyroxine for treatment of hypothyroidism or, less commonly, diffuse nontoxic goiter or thyroid carcinoma (exogenous subclinical hyperthyroidism). Endogenous subclinical hyperthyroidism may be caused by a variety of thyroid disorders that result in overproduction and release of thyroid hormones from the gland with normal/high 24-hour thyroid radioiodine uptake or by inflammation in the thyroid resulting in release of excess thyroid hormones and low 24-hour thyroid radioiodine uptake. Several groups have investigated whether persistent endogenous or exogenous subclinical hyperthyroidism, like overt hyperthyroidism, causes symptoms, adverse effects on the cardiovascular and the skeletal systems, and increased mortality, whether endogenous subclinical hyperthyroidism evolves to overt thyrotoxicosis, and whether or not it should be treated. The present report reviews the most important and recent studies of subclinical hyperthyroidism and attempts to draw conclusions based upon the literature and the authors' experience.

  17. Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer.

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    Alison M Mondul

    Full Text Available BACKGROUND: Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC Study. METHODS: Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2:1 to cases on age and date of blood collection. Odds ratios (OR and 95% confidence intervals (CI of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4, thyroid-stimulating hormone (TSH, thyroid-binding globulin (TBG, and by categories of thyroid status. RESULTS: Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI: 0.51-0.97, p = 0.03. When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p = 0.006. We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9. CONCLUSIONS: In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

  18. Paracrine interactions of thyroid hormones and thyroid stimulation hormone in the female reproductive tract have an impact on female fertility

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    Anneli eStavreus-Evers

    2012-03-01

    Full Text Available Thyroid disease often causes menstrual disturbances and infertility problems. Thyroid hormone (TH acts through its receptors, transcription factors present in most cell types in the body. Thyroid stimulating hormone (TSH stimulates TH synthesis in the thyroid gland, but seems to have other functions as well in the female reproductive tract. The receptors of both TH and TSH increase in the receptive endometrium, suggesting that they are important for implantation, possible by influencing inflammatory mediators such as LIF. The roles of these receptors in the ovary need further studies. However, it is likely that the thyroid system is important for both follicular and embryo development. The association between thyroid disease and infertility indicate that TH and TSH affect the endometrium and ovary on the paracrine level.

  19. Circulating thyroid stimulating hormone receptor messenger RNA and differentiated thyroid cancer: A diagnostic meta-analysis

    Science.gov (United States)

    Kong, Chao-Yue; Li, Zhan-Ming; Wang, Li-Shun

    2017-01-01

    Thyroid stimulating hormone receptor messenger RNA (TSHR-mRNA) is over-expressed in thyroid cancer patients, which indicates that TSHR-mRNA is a potential biomarker of thyroid cancer. However, system evaluation for TSHR-mRNA as a diagnostic biomarker of thyroid cancer is deficient. The performance of TSHR-mRNA for thyroid cancer diagnosis was evaluated in this study. Three common international databases as well as a Chinese database were applied for literature researching. Quality assessment of the included literatures was conducted by the QUADAS-2 tool. Totally, 1027 patients from nine studies eligible for the meta-analysis were included in this study. Global sensitivity and specificity for the positivity of TSHR-mRNA in the thyroid cancer diagnosis is 72% and 82%. The value of AUC for this test performance was 0.84. Our meta-analysis suggests that TSHR-mRNA might be a potential biomarker to complete present diagnostic methods for early and precision diagnosis of thyroid cancer. Notably, this findings need validation thorough large-scale clinical studies. PMID:28036261

  20. Serum thyroid-stimulating hormone and interleukin-8 levels in boys with autism spectrum disorder.

    Science.gov (United States)

    Singh, Sarika; Yazdani, Umar; Gadad, Bharathi; Zaman, Sayed; Hynan, Linda S; Roatch, Nichole; Schutte, Claire; Marti, C Nathan; Hewitson, Laura; German, Dwight C

    2017-06-02

    Autism spectrum disorder (ASD) affects approximately 1 in 68 children in the USA. An ASD blood biomarker may enable early diagnosis and/or identification of new therapeutic targets. Serum samples from ASD and typically developing (TD) boys (n = 30/group) were screened for differences in 110 proteins using a multiplex immunoassay. Eleven proteins were found that together could confirm ASD with modest accuracy using multiple training and test sets. Two of the 11 proteins identified here were further tested using a different detection platform and with a larger sample of ASD and TD boys. The two proteins, thyroid-stimulating hormone (TSH) and interleukin-8 (IL-8), have been previously identified as putative biomarkers for ASD. TSH levels were significantly lower in ASD boys, whereas IL-8 levels were significantly elevated. The diagnostic accuracy for ASD based upon TSH or IL-8 levels alone varied from 74 to 76%, but using both proteins together, the diagnostic accuracy increased to 82%. In addition, TSH levels were negatively correlated with the Autism Diagnostic Observation Schedule subdomain scores. These data suggest that a panel of proteins may be useful as a putative blood biomarker for ASD.

  1. Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes.

    Science.gov (United States)

    Paolino, Donatella; Cosco, Donato; Gaspari, Marco; Celano, Marilena; Wolfram, Joy; Voce, Pasquale; Puxeddu, Efisio; Filetti, Sebastiano; Celia, Christian; Ferrari, Mauro; Russo, Diego; Fresta, Massimo

    2014-08-01

    Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. [Thyroid stimulating immunoglobulin bioassay using cultured normal human thyroid cells].

    Science.gov (United States)

    Ando, M; Yamauchi, K; Tanaka, H; Mori, Y; Takatsuki, K; Yamamoto, M; Matsui, N; Tomita, A

    1985-08-20

    It is currently believed that the thyroid stimulating immunoglobulin (TSI) of Graves' disease is involved in the pathogenesis of hyperthyroidism through the stimulation of the adenylate cyclase-cyclic AMP system. To evaluate this mechanism, TSI in the serum of patients with Graves' disease was determined by its ability to generate cyclic AMP (cAMP) in monolayer cells prepared from a normal thyroid gland. The thyroid tissue was digested with collagenase, and the liberated follicles were collected from the supernatant and cultured for 7 days. One gram of thyroid tissue yielded more than 1 X 10(7) monolayer cells which were stored in aliquots at -80C. Cells (1 approximately 2 X 10(4)/0.28 cm2 microtiter well) were incubated for 4 hours in 0.2 ml Hanks solution poor in NaCl, with various amounts of bovine TSH (bTSH) or 1.5 mg/ml Graves' serum IgG extracted by polyethylene glycol. cAMP accumulated in medium and cells was measured by RIA. Total cAMP (both medium and cells) was about 4 times higher when NaCl was deleted from Hanks solution. Moreover, as more than 90% of the cAMP was released into the medium, it was possible to omit the measurement of cellular cAMP, which requires extraction. The increase in medium cAMP concentration was dependent upon the number of cells, incubation time, and dose of bTSH. Time course and dose response curves in medium cAMP stimulated by IgG from 3 Graves' patients paralleled those of bTSH equivalent units. Accordingly, TSI activity could be expressed in bTSH equivalent units (bTSH microUeq). The assay could detect 1.0 or 3.3 microU/ml of bTSH and was highly reproducible. TSI activity in all of 16 IgGs from normal subjects was under 3.3 bTSH microUeq/ml, while it was greater than 3.3 bTSH microUeq/ml in IgGs from 33 of 37 (89%) untreated patients with Graves disease. Of the 13 patients followed for 2 to 7 months while on antithyroid drugs, 12 had greater than 3.3 bTSH microUeq/ml and, with the exception of one, all showed a decrease in

  3. Endogenous excitatory amino acid neurotransmission regulates thyroid-stimulating hormone and thyroid hormone secretion in conscious freely moving male rats.

    Science.gov (United States)

    Arufe, M C; Durán, R; Perez-Vences, D; Alfonso, M

    2002-04-01

    The role of neurotransmission of endogenous excitatory amino acid (EAA) on serum thyroid hormones and thyroid-stimulating hormone (TSH) levels was examined in conscious and freely moving adult male Sprague-Dawley rats. The rats were cannulated at the third ventricle 2 d before the experiments. Several glutamate receptor agonists, such as kainic acid and domoic acid, and antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine (MK-801) were administered into the third ventricle. Serum TSH levels were assesed by radioimmunoassay, and serum thyroid hormone levels were assessed by enzyme immunoassay. The results showed that the administration of CNQX and MK-801 produced a decrease in serum levels of TSH and thyroid hormones. The administration of kainic acid and domoic acid increased TSH concentrations, whereas CNQX completely blocked the release of TSH induced by kainic acid and domoic acid. These results suggest the importance of endogenous EAA in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the role of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the stimulatory effect of EAAs on the pituitary-thyroid axis.

  4. Neonatal thyroid-stimulating hormone concentrations in Belgium: a useful indicator for detecting mild iodine deficiency?

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    Stefanie Vandevijvere

    Full Text Available It has been proposed that neonatal thyroid-stimulating hormone (TSH concentrations are a good indicator of iodine deficiency in the population. A frequency of neonatal TSH concentrations above 5 mU/L below 3% has been proposed as the threshold indicating iodine sufficiency. The objective of the present study was to evaluate feasibility and usefulness of nation-wide neonatal TSH concentration screening results to assess iodine status in Belgium. All newborns born in Belgium during the period 2009-2011 (n = 377713 were included in the study, except those suffering from congenital hypothyroidism and premature neonates. The frequency of neonatal TSH concentrations above 5 mU/L from 2009 to 2011 in Belgium fluctuated between 2.6 and 3.3% in the centres using the same TSH assay. There was a significant inverse association between neonatal TSH level and birth weight. The longer the duration between birth and screening, the lower the TSH level. Neonatal TSH levels were significantly lower in winter than in spring or autumn and significantly lower in spring and summer than in autumn while significantly higher in spring compared to summer. In conclusion, despite that pregnant women in Belgium are mildly iodine deficient, the frequency of neonatal TSH concentrations above 5 mU/L was very low, suggesting that the neonatal TSH threshold proposed for detecting iodine deficiency needs to be re-evaluated. Although neonatal TSH is useful to detect severe iodine deficiency, it should not be recommended presently for the evaluation of iodine status in mildly iodine deficient regions.

  5. Thyroid stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers' diseases

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    Laura Sterian Ward

    2000-09-01

    Full Text Available CONTEXT: Screening programs not only offer the opportunity to trace and treat almost all cases of congenital hypothyroidism but also mean large savings to the health system. However, carefully planned strategies are necessary to extend their benefits and reduce costs. OBJECTIVE: To determine the possible influence of maternal diseases that affect maternal-fetal placenta dynamics on primary thyroid stimulating hormone (TSH screening for congenital hypothyroidism. DESIGN: Prospective non-randomized clinical trial with at least 3 months of follow-up. SETTING: A public university referral center [CAISM/Hospital das Clínicas, Faculty of Medicine, University of Campinas, Campinas, SP]. PARTICIPANTS: 415 neonates divided into 5 groups: eighty-three infants born from cardiac mothers; 98 from mothers that had toxemia; 54 of the mothers had diabetes mellitus; 40 were HIV positive and 140 had no diseases. INTERVENTION: All newborns had cord blood samples collected on filter paper at birth. MAIN MEASUREMENTS: TSH was measured from dried blood spots using a homemade immunofluorescence assay (sensitivity in dried blood spots = 0.1 mU/L. RESULTS: There was no significant difference in the mean TSH levels among the 5 groups. Moreover, TSH levels were around 5 mU/L in 48% of the newborns, indicating that our region is severely deficient in iodine. CONCLUSIONS: Our results indicate that primary TSH screening programs using cord blood are not affected by maternal diseases. We suggest that, besides its technical advantages over heel punctures with T4 primary approaches, neonatal screening using primary cord blood TSH may also be used as a monitoring tool for evaluation and control of iodine deficiency disorders (IDD.

  6. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

    Science.gov (United States)

    Perez-Ruiz, Fernando; Chinchilla, Sandra Pamela; Atxotegi, Joana; Urionagüena, Irati; Herrero-Beites, Ana Maria; Aniel-Quiroga, Maria Angeles

    2015-11-01

    Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.

  7. High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women.

    Science.gov (United States)

    Lambrinoudaki, Irene; Armeni, Eleni; Rizos, Demetrios; Georgiopoulos, Georgios; Kazani, Maria; Alexandrou, Andreas; Deligeoroglou, Efthymios; Livada, Alexandra; Psychas, Charalampos; Creatsa, Maria; Bouboulis, George; Alevizaki, Maria; Stamatelopoulos, Kimon

    2012-03-01

    Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4-4.5 μIU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima-media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 μIU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 μIU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 μIU/ml were the only significant predictors of PWV (TSH, β-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature.

  8. Plasma Retinol, Thyroid Stimulating Hormone and Zinc as Predictors of Bone Mineral Density Status

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    Shawkia S. A. El-Sherbeny*, Effat A. A., Afifi**, Wafaa M. A. Saleh**, Asmaa, M

    2006-12-01

    Full Text Available Background: Conflicting results on the association between serum retinol level and bone mineral density (BMD have been published. Thyroid hormones are essential for skeletal development and have direct effect on bone formation and resorption. Bone has one of the highest concentrations of zinc of all tissues, and has been shown to release zinc during deficiency for soft tissue metabolism. Objective: The objective of this study was to assess the relation between plasma levels of retinol, thyroid stimulating hormone (TSH & zinc and BMD of Egyptian adolescents and adults. Method: The study was a part of a cross sectional national survey conducted by National Nutrition Institute. The sample was a multistage stratified random. Target individuals were classified into two age groups (10- 18 and 28- 59 years. Bone mineral density and plasma levels of retinol, TSH and zinc were determined. Results: Low and high plasma retinol levels were more prevalent among osteoporotic adolescent and adult males respectively than in normal subjects.. The reverse was observed in adult females. Bone mineral density correlated negatively with plasma retinol level in adult males and females and positively in adolescent males, while among females the association was significant (P = 0.030 and stronger. The highest deficiency of TSH was found among adult and adolescent osteoporotic males, followed by osteopenic adult males and adolescent females. Highly statistically significant difference (P < 0.001 existed between osteoporotic and normal adult males concerning TSH deficiency. The prevalence of zinc deficiency ranged from 5.7% to 9.5% for all target individuals. Plasma Zn levels were correlated negatively with bone mineral density in adult males and females. Conclusion: The results of this study reflects the controversy on the association of plasma retinol and BMD. However, the predominant finding revealed that both low and high plasna retinol levels compromise bone health

  9. Neonatal iodine status survey by thyroid-stimulating hormone screening in Surabaya

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    Connie Untario

    2012-09-01

    Full Text Available Background lodine deficiency disorders (IDD are a significant public health problem globally. Iodine deficiency may cause subclinical hypothyroidism during pregnancy and early infancy. Neonatal thyroid screening of serum thyroid-stimulating hormone (TSH to detected hypothyroidism may olso be used to determine the prevcalence of IDD in a population. Previous studies reported mild IDD status in differen parts of Indonesia Objective To evaluate the iodine status of neonates born in Mitra Keluarga Surabaya Hospital (MKSH by TSH screening over a 6-year period. Methods This is a cross-sectional and hospital-based study conducted in MKSH from January 2005 to December 2010. Of the 5,619 infants took part in this study. Blood specimens for TSH measurement were collected from subjects 2 to 6 days after birth, and sent to a reference laboraratory for evaluation. Using the neonatal TSH values, the iodine deficiency level of the group was determined according to the WHO/UNICEF/International Council for the Control of IDD criteria Results A total of 3,349 newborn babies underwent neonatal TSH screening in MKSH. Subjects’ mean TSH concentration was 5.14 mIU/L. A TSH concentration > 5mIU/L was found in 1270 (37.9% subjects, 166 (27.6% in 2005, 252 (44.0% in 2006, 331 (47.1% in 2007, 356 (57.7% in 2008, 114 (20.7% in 2009 and 51 (16.8% in 2010. On the basis of the WHO/UNICEF/International Council for the Control of Iodine Deficiency Disorder criteria, this frequency corresponded to a moderate level of IDD. Twenty-two neonates had TSH > 20 mIU/L from which 2 infants were confirmed positive for hypothyroidism. Conclusion A 6-year study of 3,349 newborns screenerd for TSH revealed that 37.9% of subjects had TSH concentration of more than 5mIU/L. this frequency indicates a moderate level of IDD in the study population.

  10. Is Very High Thyroid Stimulating Hormone Level Required in Differentiated Thyroid Cancer for Ablation Success?

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    Zekiye Hasbek

    2016-06-01

    Full Text Available Objective: Remnant ablation with radioactive iodine (I-131 is a successful form of treatment that aims to destroy the remaining residual tissue and/or metastatic tissue after total thyroidectomy in differentiated thyroid cancer (DTC patients. High level of thyroid stimulating hormone (TSH (≥30 mIU/L is recommended for success of ablation treatment. In this retrospective study, our aim was to investigate whether the TSH levels at the time of ablation effect the success of radioactive iodine remnant ablation. Methods: Patients who were diagnosed with DTC, treated with bilateral total/near total thyroidectomy and who were referred for I-131 remnant ablation were included in this study. Patients with undetectable TSH-stimulated serum thyroglobulin (Tg level, normal physical examination, negative results on whole body scan with I-131, and no evidence of neck lymph node metastasis on ultrasound were defined as disease-free. The correlation between TSH level at the time of ablation and ablation success was assessed. Results: Two hundred sixty one consecutive patients were included in the present study. Mean TSH level was 19.47±6 mIU/L in the 34 patients with TSH <30 mIU/L, while mean TSH level was 73.65±27 mIU/L in the 227 patients with TSH ≥30 mIU/L during I-131 remnant ablation. Ablation was unsuccessful in only one patient with TSH <30 mIU/L who had lung metastasis. Ablation was unsuccessful in 5.1% of patients with TSH ≥30 mIU/L. The effect of TSH level was not significant on ablation success (p=0.472. Conclusion: In conclusion, we think that a high TSH serum level alone is not a factor for the success of ablation. Age, presence of metastasis, extent of residual thyroid mass should also be considered. Especially, in the presence of metastatic tissue, obtaining adequate increase in TSH level is not always possible. The success of ablation at lower levels of TSH elevations may be sufficient for patients, and long-term hypothyroidism may not

  11. Melatonin in the thyroid gland: regulation by thyroid-stimulating hormone and role in thyroglobulin gene expression.

    Science.gov (United States)

    Garcia-Marin, R; Fernandez-Santos, J M; Morillo-Bernal, J; Gordillo-Martinez, F; Vazquez-Roman, V; Utrilla, J C; Carrillo-Vico, A; Guerrero, J M; Martin-Lacave, I

    2015-10-01

    Melatonin is an indoleamine with multiple functions in both plant and animal species. In addition to data in literature describing many other important roles for melatonin, such as antioxidant, circadian rhythm controlling, anti-aging, antiproliferative or immunomodulatory activities, our group recently reported that thyroid C-cells synthesize melatonin and suggested a paracrine role for this molecule in the regulation of thyroid activity. To discern the role played by melatonin at thyroid level and its involvement in the hypothalamic-pituitary-thyroid axis, in the present study we have analyzed the effect of thyrotropin in the regulation of the enzymatic machinery for melatonin biosynthesis in C cells as well as the effect of melatonin in the regulation of thyroid hormone biosynthesis in thyrocytes. Our results show that the key enzymes for melatonin biosynthesis (AANAT and ASMT) are regulated by thyroid-stimulating hormone. Furthermore, exogenous melatonin increases thyroglobulin expression at mRNA and protein levels on cultured thyrocytes and this effect is not strictly mediated by the upregulation of TTF1 or, noteworthy, PAX8 transcription factors. The present data show that thyroid C-cells synthesize melatonin under thyroid-stimulating hormone control and, consistently with previous data, support the hypothesis of a paracrine role for C-cell-synthesised melatonin within the thyroid gland. Additionally, in the present study we show evidence for the involvement of melatonin in thyroid function by directly-regulating thyroglobulin gene expression in follicular cells.

  12. Ghrelin suppresses nocturnal secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in patients with major depression.

    Science.gov (United States)

    Kluge, Michael; Schmidt, Doreen; Uhr, Manfred; Steiger, Axel

    2013-09-01

    Major depression is associated with various endocrine disturbances. Apart from the well-known hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, also the function of the hypothalamic-pituitary-gonadal (HPG) axis and of the hypothalamic-pituitary-thyroid (HPT) axis may be altered compared to healthy subjects. The orexigenic hormone ghrelin is involved in mood regulation and may have antidepressant effects. In addition, it has been shown to suppress secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in healthy subjects. Aim of this study was therefore to test the effect of ghrelin on the activity of the HPG and HPT axis in patients with major depression. Therefore, secretion profiles of LH and TSH were determined in 14 unmedicated patients with major depression (7 women) twice, receiving 50 μg ghrelin or placebo at 2200, 2300, 0000, and 0100 h. LH secretion after ghrelin injection as assessed by the AUC (4.05 ± 1.18 mlIU min/ml) was significantly (P = 0.049) lower than after placebo injection (4.75 ± 1.33 mlIU min/ml) during the predefined intervention period (2220-0200 h). In addition, LH pulses occurred significantly (P = 0.045) less frequently after ghrelin injection (3.2 ± 1.4) than after placebo injection (3.9 ± 1.7). Mean TSH plasma levels were significantly lower at 0240 h and from 0320 until 0420 h after ghrelin injection than after placebo injection. In conclusion, ghrelin suppressed nocturnal secretion of LH and TSH in patients with major depression. However, these effects were weaker than previously shown in healthy subjects.

  13. Thyroid-Stimulating Hormone, White Matter Hyperintensities, and Functional Outcome in Acute Ischemic Stroke Patients

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    Christopher O. Leonards

    2014-03-01

    Full Text Available Background: Thyroid-stimulating hormone (TSH concentrations are frequently altered in acute ischemic stroke patients. It is becoming increasingly apparent that various hormones in the hypothalamus-pituitary-thyroid axis may be associated with functional stroke outcome. We have previously shown that white matter hyperintensities (WMH of presumed vascular origin are strong indicators of functional outcome. It is unclear whether an association exists between WMH and TSH. We therefore sought to determine whether TSH levels, measured in acute ischemic stroke patients, are associated with WMH and functional outcome. Methods: We analyzed all first ischemic stroke patients who participated in the Berlin ‘Cream & Sugar' Study (NCT 01378468 and completed a 1-year follow-up assessment from January 2009 to March 2013. Patients were stratified into 3 groups: (1 low TSH (0.1-0.44 μU/ml; (2 normal TSH (0.44-2.5 μU/ml, and (3 high TSH (2.5-20 μU/ml. WMH were assessed using the Fazekas and Wahlund visual rating scales. Functional outcome was assessed using the modified Rankin Scale and was performed via telephone at 1 year by a certified rater. Results: 183 patients were included [median age 66, interquartile range (IQR 54-75; 33% females; median National Institute of Health Stroke Scale 3, IQR 1-4, range 0-24]. Venous samples were collected a median of 4 days (IQR 3-5 following initial symptom onset between 8 and 9 a.m. following a 10-hour fast. Patients with normal TSH levels (n = 132; 72% had significantly higher rates of prestroke diabetes than patients with high TSH levels (normal TSH 17%; high TSH 1%; p = 0.03. Additionally, patients with normal TSH levels tended to have higher estimated glomerular filtration rates than patients with high and low TSH concentrations (normal TSH median estimated glomerular filtration rates: 83 ml/min/1.73 m2; high TSH median estimated glomerular filtration rates: 76 ml/min/1.73 m2; low TSH median: 78 ml/min/1.73 m2; p

  14. Reliability of the thyroid stimulating hormone receptor antibodies level determination in diagnosing and prognosing of immunogenic hyperthyroidism

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    Aleksić Aleksandar Z.

    2009-01-01

    Full Text Available Background/Aim. Graves disease (GD is defined as hyperthyroidism with diffuse goiter caused by immunogenic disturbances. Antibodies to the thyroid stimulating hormone (TSH receptors of thyroid gland (TRAb have crucial pathogenetic importance in the development and maintenance of autoimmune hyperthyroidism. The aim of this study was to identify sensitivity, specificity, positive an negative predictive value of TRAb level in sera of patients with GD as well as to estimate significance of TRAb level for remission and GD relapses occurrence. Methods. We studied prospectively and partly retrospectively 149 patients, 109 female and 40 male patients, 5-78 years old, in the period 1982-2007. There were 96 patients with GD. The control group consisted of 53 patients, 21 with hyperthyroidism of second etiology and 32 patients on amiodarone therapy, with or without thyroid dysfunction TRAb was measured by radioreceptor assay (TRAK Assay and DYNO Test TRAK Human Brahms Diagnostica GMBH. Results. According to the results the sensitivity (Sn of TRAb test was 80%, specificity (Sp 100%, positive predictive value (PP 100% and negative predictive value (NP 83%. Also, the Sn of hTRAb test was 94%, Sp 100%, PP 100% and NP 94%. Our results show that an increased level of TRAb/hTRAb at the beginning of the disease and the level at the end of medical therapy is associated with an increased number of GD relapses and a shorter remission duration. Conclusion. Detection and measurement of TRAb in serum is a very sensitive method for diagnosing GD and very highly specific in vitro method for differential diagnosis of various forms of hyperthyroidism. Clinical significance of differentiating various forms of hyperthyroidism, using this in vitro assay, lays in adequate therapeutic choice for these entities.

  15. Thyroid-stimulating hormone-secreting pituitary adenoma presenting with recurrent hyperthyroidism in post-treated Graves’ disease: a case report

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    Ogawa Yoshikazu

    2013-01-01

    Full Text Available Abstract Introduction The coexistence of autoimmune hyperthyroid disease and thyroid-stimulating hormone-secreting pituitary adenoma is rare. The simple presumption of coincidence of these two diseases has a calculated incidence of less than one/several hundred million, and only four cases with histological confirmation have been reported. A rapid decrease in thyroid-stimulating hormone level after pituitary tumor removal may induce subsequent activation of autoimmune responses against the thyroid gland. We report the first case of a sequential and paradoxical occurrence of Graves’ disease and a thyroid-stimulating hormone-secreting pituitary adenoma. Case presentation A 32-year-old Japanese woman had recurrent hyperthyroidism. She had a history of Graves’ hyperthyroidism, which had been successfully treated with propylthiouracil. A head magnetic resonance imaging showed a less enhanced area in the left lateral wing of her sella turcica. Transsphenoidal surgery was performed, and the diagnosis was established as thyroid-stimulating hormone-secreting plurihormonal adenoma. A rapid reduction in thyroid hormone levels was achieved, and her blood pressure was normalized after the operation. Conclusion Although incidental occurrence is the most probable etiology, long and repeated followup examinations of both thyroid and pituitary gland should be performed in patients with an atypical clinical course.

  16. Nanogold-polyaniline-nanogold microspheres-functionalized molecular tags for sensitive electrochemical immunoassay of thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Cui Yuling; Chen Huafeng; Hou Li; Zhang Bing; Liu Bingqian; Chen Guonan [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Province Key Laboratory of Analysis and Detection for Food Safety, Department of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350108 (China); Tang Dianping, E-mail: dianping.tang@fzu.edu.cn [Ministry of Education Key Laboratory of Analysis and Detection for Food Safety, Fujian Province Key Laboratory of Analysis and Detection for Food Safety, Department of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350108 (China)

    2012-08-13

    Highlights: Black-Right-Pointing-Pointer A novel immunosensing strategy was designed for detection of thyroid-stimulating hormone. Black-Right-Pointing-Pointer Using nanogold-polyaniline-nanogold microspheres as molecular tags. Black-Right-Pointing-Pointer Improvement of electrochemical activity of nanolabels. Black-Right-Pointing-Pointer Combination enzyme labels with nanolabels for signal amplification. - Abstract: Methods based on nanomaterial labels have been developed for electrochemical immunosensors and immunoassays, but most involved low sensitivity. Herein a novel class of molecular tags, nanogold-polyaniline-nanogold microspheres (GPGs), was first synthesized and functionalized with horseradish peroxidase-conjugated thyroid-stimulating hormone antibody (HRP-Ab{sub 2}) for sensitive electrochemical immunoassay of thyroid-stimulating hormone (TSH). X-ray diffraction, confocal Raman spectroscopy, scanning electron microscope and transmission electron microscope were employed to characterize the prepared GPGs. Based on a sandwich-type immunoassay format, the assay was performed in pH 5.0 acetate buffer containing 6.0 mmol L{sup -1} H{sub 2}O{sub 2} by using GPG-labeled HRP-Ab{sub 2} as molecular tags. Compared with pure polyaniline nanospheres and gold nanoparticles alone, the GPG hybrid nanostructures increased the surface area of the nanomaterials, and enhanced the immobilized amount of HRP-Ab{sub 2}. Several labeling protocols comprising HRP-Ab{sub 2}, nanogold particle-labeled HRP-Ab{sub 2}, and polyaniline nanospheres-labeled HRP-Ab{sub 2}, were also investigated for determination of TSH and improved analytical features were obtained by using the GPG-labeled HRP-Ab{sub 2}. With the GPG labeling method, the effects of incubation time and pH of acetate buffer on the current responses of the immunosensors were also studied. The strong attachment of HRP-Ab{sub 2} to the GPGs resulted in a good repeatability and intermediate precision down to 7%. The dynamic

  17. Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism.

    Science.gov (United States)

    Bals-Pratsch, M; De Geyter, C; Müller, T; Frieling, U; Lerchl, A; Pirke, K M; Hanker, J P; Becker-Carus, C; Nieschlag, E

    1997-05-01

    Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female

  18. Composite reference interval for thyroid-stimulating hormone and free thyroxine, comparison with common cutoff values, and reconsideration of subclinical thyroid disease.

    NARCIS (Netherlands)

    Ross, H.A.; Heijer, M. den; Hermus, A.R.M.M.; Sweep, C.G.J.

    2009-01-01

    BACKGROUND: Examination of the 2-dimensional probability distribution of thyroid-stimulating hormone (TSH) and free thyroxine (FT(4)) shows that the widths of the TSH and FT(4) reference intervals derived from this bivariate distribution are mutually interdependent, an aspect commonly ignored when i

  19. Is suppressed thyroid-stimulating hormone (TSH) associated with subclinical depression in the Danish General Suburban Population Study?

    DEFF Research Database (Denmark)

    Kvetny, Jan; Ellervik, Christina; Bech, Per

    2015-01-01

    phase, including 14,787 individuals, we have focused on suppressed TSH (thyroid-stimulating hormone) and depression. AIMS: To evaluate to what extent suppressed TSH is associated with subclinical depression. METHODS: The total scores of the Major Depression Inventory (MDI) were used to evaluate...... subclinical depression, both by its total score and by an algorithm of the subthreshold depressed by presence of at least three of the 10 ICD-10 depression symptoms. Serum levels of TSH were used to classify the individuals into suppressed (TSH ...BACKGROUND: The first phase of the Danish General Suburban Population Study (GESUS) including 8214 individuals was an attempt to evaluate the association between subclinical hypothyroidism without or with elevated peroxidase antibodies and depression. No such association was found. In the second...

  20. Diagnosis and discrimination of autoimmune Graves' disease and Hashimoto's disease using thyroid-stimulating hormone receptor-containing recombinant proteoliposomes.

    Science.gov (United States)

    Fukushima, Hidetaka; Matsuo, Hideaki; Imamura, Koji; Morino, Kazuhiko; Okumura, Katsuzumi; Tsumoto, Kanta; Yoshimura, Tetsuro

    2009-12-01

    Graves' disease (GD) is an autoimmune disease of the thyroid gland caused by autoantibodies against thyroid-stimulating hormone receptor (TSHR). Currently, the diagnostic test for TSHR autoantibodies is based on an indirect competitive binding assay that measures the ability of TSHR autoantibodies to inhibit the binding of thyroid-stimulating hormone (TSH) to TSHR. Here, we have developed a specific and direct diagnostic method for autoantibodies in GD that incorporates immobilized TSHR-containing recombinant proteoliposomes into an enzyme-linked immunosorbent assay (ELISA). To reduce non-specific binding of autoantibodies to recombinant proteoliposomes, we investigated the effect of polyethylene glycol (PEG)-lipid on the binding of commercially available anti-TSHR antibodies (aTSHRAb). The incorporation of PEG-lipids into liposomes decreased non-specific binding, as compared to liposomes that did not contain PEG-lipids, and the addition of blocking reagents further decreased non-specific reactivity. aTSHRAb exhibited higher reactivity towards PEG-modified TSHR recombinant proteoliposomes than PEG-modified liposomes without TSHR (bare liposomes). Importantly, serum autoantibodies from patients with GD, which is associated with hyperthyroidism, exhibited remarkably specific binding to TSHR recombinant proteoliposomes. Serum autoantibodies from patients with Hashimoto's disease (HD), which is associated with hypothyroidism, also reacted specifically with proteoliposomal TSHR. These results suggest that immobilized TSHR recombinant proteoliposomes can serve as a direct diagnostic test for GD and HD. Furthermore, given that there is no competition test currently available for detecting autoantibodies in HD, the combination of TSHR recombinant proteoliposome ELISA and indirect competitive TSHR binding assay might be an effective way to discriminate between GD and HD.

  1. 重组人促甲状腺激素在131I治疗分化型甲状腺癌中的应用研究%Recombinant human thyroid stimulating hormone-aided 131I treatment for differentiated thyroid carcinoma

    Institute of Scientific and Technical Information of China (English)

    王中京; 张旭艳; 陆涤宇; 孙敏娴; 徐子辉; 丁胜

    2016-01-01

    Objective To observe the infiuence of recombinant human thyroid stimulating hormone(rhTSH)-aided 131I treatment for patients with differentiated thyroid carcinoma (DTC)and its efficacy on thyroid hormone level.Methods 20 cases with DTC admitted from Nov.2010 to Jun.2014 were divided into 2 groups.11 cases received rhTSH-aided 131I treatment (rhTSH-aided group)and the other 9 cases received 131I treatment after thyroid hormone withdrawal (THs withdrawal group).The influence of the 2 treatment methods on the serum TSH,FT3,FT4,Tg was evaluated,and the therapeutic effects were assessed according to 131I whole body scintigraphy (WBS)and Tg-negative rate.Results The serum TSH was significantly higher in rhTSH-aided group than that before treatment(t=27.70,P< 0.001)and in THs withdrawal group (t=7.18,P<0.001).TSH levels of all patients were>30 mU/L.WBS displayed that the thyroid remnant clearance rate was 72.73%(8 cases)nd 66.67%(6 cases)respectively in rhTSH-aided group and THs with-drawal group and there was no statistical difference between the 2 groups(x2=0.178,0.673).Conclusion The rhTsH treatment can help to accomplish the preparation of 131I treatment for DTC and acquire satisfactory ablation efficacy.%目的 探讨重组人促甲状腺激素(recombinant human thyroid stimulating hormone,rhTSH)介导131I治疗分化型甲状腺癌(differentiated thyroid carcinoma,DTC)的清甲成功率及对甲状腺激素的影响.方法 将武汉市中心医院内分泌科及核医学科2010年11月至2014年6月收治的20例DTC分别分为接受rhTSH介导的131I清甲治疗(rhTSH介导组)11例和甲状腺激素撤退后的131I清甲治疗(THs撤退组)9例,评价2种治疗方法对血清TSH、FT3、FT4、甲状腺球蛋白(Tg)的影响,并据诊断剂量131I全身显像及Tg阴性率评价2组131I清甲效果.结果 rhTSH介导治疗后,患者血清TSH显著高于治疗前,差异有统计学意义(t=27.70,P<0.001),并高于THs撤退组(t=7.18,P<0.001),

  2. No association between elevated thyroid-stimulating hormone (TSH at birth and parent-reported problem behavior at preschool age.

    Directory of Open Access Journals (Sweden)

    Caroline Trumpff

    2016-12-01

    Full Text Available Objectives: Mild level of iodine deficiency during pregnancy may reduce maternal thyroid hormone production and supply to the fetus hence affecting brain neurodevelopment. The aim of the present study was to investigate the association between elevated neonatal thyroid stimulating hormone (TSH level (>5 mU/L, used as a marker of maternal mild iodine deficiency during late pregnancy, and behavioral development of preschool children.Methods: This retrospective cohort study included 310 Belgian mothers and their children aged 4-5 years old with TSH levels in the range of 0.45-15 mU/L at birth. The TSH level was measured in dried blood spots on filter paper collected by heel stick three to five days after birth. Low birth weight, prematurely born children or children with congenital hypothyroidism were excluded. The degree of behavioral problems was evaluated using the Child Behavior Check List (CBCL for age 1½ to 5 Years questionnaire. Relevant socioeconomic, maternal and child factors were also collected.Results: TSH concentrations and CBCL scores were not associated both in univariate analysis and when adjusting for confounding factors in multivariate analysis.Discussion: Elevated TSH concentrations measured at birth was not associated with behavioral development scores.

  3. HiLo: Multicentre randomized phase III clinical trial of high vs low dose radioiodine, with or without recombinant human thyroid stimulating hormone (rhTSH), for remnant ablation for differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mallick, U. [Freeman Hospital, Newcastle, Newcastle upon Tyne (United Kingdom); Harmer, C.; Clarke, S.; Moss, L.; Nicol, A.; Clarke, P.; Smellie, J.; McCready, R.; Farnell, K.; Franklyn, J.; John, R.; Nutting, C.; Yap, B.; Lemon, C.; Wadlsey, J.; Gerrard, G.; Roques, T.; Macias, E.; Whitaker, S.; Abdul-Hamid, A.; Alvarez, P.; Kadalayil, L.; Hackshaw, A.

    2012-07-01

    Recommended treatment for most patients with differentiated thyroid cancer is surgery followed by radioiodine ablation. Current practice in many centres is to use a high administered activity of 3.7 GBq (100 mCi). However, a lower activity (1.1 GBq or 30 mCi) has advantages including a shorter stay in hospital isolation and lower risk of side effects, including the risk of a second cancer. Also, Thyrogen (rhTSH) allows patients to continue thyroid hormone replacement during ablation, avoiding symptoms of hypothyroidism and also reduces total body radiation dose. We conducted a large randomized factorial multi centre trial to simultaneously address whether ablation success rates are similar using (i) either 1.1 GBq or 3.7 GBq, and (ii) either Thyrogen or thyroid hormone withdrawal. It is the first ever national prospective trial in thyroid cancer in the UK. Final results will be available in 2011

  4. 促甲状腺激素与亚临床性甲状腺功能异常%Thyroid stimulating hormone and subclinical thyroid dysfunction

    Institute of Scientific and Technical Information of China (English)

    郭永铁

    2008-01-01

    Subclinical thyroid dysfunction has mild clinical symptoms. It is nonspecific and not so noticeable. It performs only for thyroid stimulating hormone rise and decline. The value of early diagnosis and treatment of thyroid stimulating hormone in subclinical thyroid dysfunction were reviewed.%亚临床性甲状腺功能异常的临床症状轻微、无特异性、不易被察觉,只表现为促甲状腺激素的上升、下降.对促甲状腺激素在亚临床性甲状腺功能异常中早期诊治的价值进行综述.

  5. Clinical Association of Thyroid Stimulating Hormone Receptor Antibody Levels with Disease Severity in the Chronic Inactive Stage of Graves' Orbitopathy.

    Science.gov (United States)

    Woo, Young Jae; Jang, Sun Young; Lim, Tyler Hyung Taek; Yoon, Jin Sook

    2015-08-01

    To investigate associations between serum thyroid stimulating hormone (TSH) receptor antibody (TRAb) levels and Graves' orbitopathy (GO) activity/severity in chronic-stage GO and compare the performance of two newly-developed TRAb assays (third-generation TSH-binding inhibition immunoglobulin [TBII] assay versus Mc4 thyroid-stimulating immunoglobulin [TSI] bioassay). This study is a retrospective review of medical charts and blood tests from Korean GO patients who first visited the departments of ophthalmology and endocrinology, Yonsei University College of Medicine from January 2008 to December 2011, were diagnosed with GO and Graves' hyperthyroidism, and were followed up for ≥18 months. Third-generation M22-TBII and Mc4-TSI assays were performed in the chronic-inactive GO patients in whom euthyroidism status was restored. Patients' GO activity/severity clinical activity scores (CAS), and modified NOSPECS scores were examined for a correlation with TRAb assays. Fifty patients (mean age, 41.3 years; 41 females) were analyzed. The mean duration of Graves' hyperthyroidism symptom was 63 months (range, 18 to 401 months) and that of GO was 46 months (range, 18 to 240 months). All patients had been treated previously with anti-thyroid drugs for a median period of 52.3 months, and two patients underwent either radioiodine therapy or total thyroidectomy. Mean CAS and NOSPECS scores were 0.5 ± 0.9 (standard deviation) and 4.8 ± 3.1, respectively. Mean M22-TBII and Mc4-TSI values were 7.5 ± 10.2 IL/L and 325.9 ± 210.1 specimen-to-reference control ratio. TSI was significantly correlated with NOSPECS score (R = 0.479, p 0.05), because GO inflammatory activity subsided in the chronic stages of GO. In chronic-inactive GO after euthyroid restoration, GO activity score did not associate with serum levels of TRAb or TBII. However, levels of the functional antibody Mc4-TSI did correlate with GO severity. Therefore, the TSI bioassay is a clinically relevant measure of disease

  6. Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age.

    Science.gov (United States)

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

    2015-11-02

    The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4-6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45-15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence-third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration-a surrogate marker for MID-was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10-15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children.

  7. Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1 adipocytes through the PKA pathway.

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    Dongqing Jiang

    Full Text Available Thyroid-stimulating hormone (TSH has been shown to play an important role in the regulation of triglyceride (TG metabolism in adipose tissue. Adipose triglyceride lipase (ATGL is a rate-limiting enzyme controlling the hydrolysis of TG. Thus far, it is unclear whether TSH has a direct effect on the expression of ATGL. Because TSH function is mediated through the TSH receptor (TSHR, TSHR knockout mice (Tshr-/- mice (supplemented with thyroxine were used in this study to determine the effects of TSHR deletion on ATGL expression. These effects were verified in 3T3-L1 adipocytes and potential underlying mechanisms were explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was significantly increased compared with that in Tshr+/+ mice. ATGL expression was observed to increase with the differentiation process of 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1 adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by H89, which is a protein kinase A (PKA inhibitor. These results indicate that TSH has an inhibitory effect on ATGL expression in mature adipocytes. The associated mechanism is related to PKA activation.

  8. Thyroid-Stimulating Hormone (TSH Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age

    Directory of Open Access Journals (Sweden)

    Caroline Trumpff

    2015-11-01

    Full Text Available The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4–6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45–15 mIU/L. Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence—third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration—a surrogate marker for MID—was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10–15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children.

  9. Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

    Science.gov (United States)

    Valencia, N Arana; Thompson, D L; Mitcham, P B

    2013-05-01

    Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P sulpiride and TRH injection and were greater (P sulpiride and TRH injection, and the response was greater (P sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well).

  10. A domestication related mutation in the thyroid stimulating hormone receptor gene (TSHR) modulates photoperiodic response and reproduction in chickens.

    Science.gov (United States)

    Karlsson, Anna-Carin; Fallahshahroudi, Amir; Johnsen, Hanna; Hagenblad, Jenny; Wright, Dominic; Andersson, Leif; Jensen, Per

    2016-03-01

    The thyroid stimulating hormone receptor gene (TSHR) has been suggested to be a "domestication locus" in the chicken. A strong selective sweep over TSHR in domestic breeds together with significant effects of a mutation in the gene on several domestication related traits, indicate that the gene has been important for chicken domestication. TSHR plays a key role in the signal transduction of seasonal reproduction, which is characteristically less strict in domestic animals. We used birds from an advanced intercross line between ancestral Red Junglefowl (RJF) and domesticated White Leghorn (WL) to investigate effects of the mutation on reproductive traits as well as on TSHB, TSHR, DIO2 and DIO3 gene expression during altered day length (photoperiod). We bred chickens homozygous for either the mutation (d/d) or wild type allele (w/w), allowing assessment of the effect of genotype at this locus while also controlling for background variation in the rest of the genome. TSHR gene expression in brain was significantly lower in both d/d females and males and d/d females showed a faster onset of egg laying at sexual maturity than w/w. Furthermore, d/d males showed a reduced testicular size response to decreased day length, and lower levels of TSHB and DIO3 expression. Additionally, purebred White Leghorn females kept under natural short day length in Sweden during December had active ovaries and lower levels of TSHR and DIO3 expression compared to Red Junglefowl females kept under similar conditions. Our study indicates that the TSHR mutation affects photoperiodic response in chicken by reducing dependence of seasonal reproduction, a typical domestication feature, and may therefore have been important for chicken domestication.

  11. Clinical significance of serum levels of thyroid stimulating hormone receptor antibody in pregnant women with Graves′disease

    Institute of Scientific and Technical Information of China (English)

    Zhao Zhi-ying; Tian Jian; Zhu Li

    2010-01-01

    Objective: To investigate the clinical significance of serum thyroid stimulating hormone (TSH) receptor antibody (TRAb) levels and the antithyroid drug (ATDs) use in pregnant women with Graves′ disease in their neonatal thyroid function. Methods: The serum TRAb and T3, T4, FT3, FT4, TSH levels in 68 pregnant women with Graves′ disease and their newborns were detected by radio receptor assay (RRA) and electrical chemiluminescence immunoassay (ECLIA), respectively. Based on the maternal serum TRAb levels and the use of antithyroid drugs during pregancy, the newborns were divided into different groups. The incidence of neonatal thyroid dysfunction and its risk factors were analyzed.Results: The results showed the incidence of abnormal thyroid function of newborns was 29.4% (20/68). The proportion of neonatal thyroid dysfunction in women with high TRAb levels in the third trimester of pregnancy were significantly higher than these with normal TRAb (P<0.01). In 23 newborns whose mothers were normal in serum TRAb levels and took no ATDs during pregnancy, only one case had thyroid dysfunction within two weeks after birth, while in other 45 newborns whose mothers had a high level of serum TRAb and/or took ATDs during pregnancy, 19 developed thyroid dysfunction within two weeks after birth.Conclusion: Neonatal thyroid function depends on the balance between the transplacental TRAb and ATDs. TRAb measurement in pregnant women with Graves′ disease is of significance in evaluation of neonatal thyroid function. Elevated level of serum TRAb in the third trimester of pregnancy is a risk factor for neonatal thyroid dysfunction.

  12. Thyroid stimulating hormone receptor (TSHR intron 1 variants are major risk factors for Graves' disease in three European Caucasian cohorts.

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    Rafał Płoski

    Full Text Available BACKGROUND: The thyroid stimulating hormone receptor (TSHR gene is an established susceptibility locus for Graves' disease (GD, with recent studies refining association to two single nucleotide polymorphisms (SNPs, rs179247 and rs12101255, within TSHR intron 1. METHODOLOGY AND PRINCIPAL FINDINGS: We aimed to validate association of rs179247 and rs12101255 in Polish and UK Caucasian GD case-control subjects, determine the mode of inheritance and to see if association correlates with specific GD clinical manifestations. We investigated three case-control populations; 558 GD patients and 520 controls from Warsaw, Poland, 196 GD patients and 198 controls from Gliwice, Poland and 2504 GD patients from the UK National collection and 2784 controls from the 1958 British Birth cohort. Both rs179247 (P = 1.2×10(-2-6.2×10(-15, OR = 1.38-1.45 and rs12101255 (P = 1.0×10(-4-3.68×10(-21, OR = 1.47-1.87 exhibited strong association with GD in all three cohorts. Logistic regression suggested association of rs179247 is secondary to rs12101255 in all cohorts. Inheritance modeling suggested a co-dominant mode of inheritance in all cohorts. Genotype-phenotype correlations provided no clear evidence of association with any specific clinical characteristics. CONCLUSIONS: We have validated association of TSHR intron 1 SNPs with GD in three independent European cohorts and have demonstrated that the aetiological variant within the TSHR is likely to be in strong linkage disequilibrium with rs12101255. Fine mapping is now required to determine the exact location of the aetiological DNA variants within the TSHR.

  13. Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis.

    Science.gov (United States)

    Aizawa, Sayaka; Sakai, Takafumi; Sakata, Ichiro

    2012-03-01

    Thyroid-stimulating hormone (TSH)-producing cells of the pars tuberalis (PT) display distinct characteristics that differ from those of the pars distalis (PD). The mRNA expression of TSHβ and αGSU in PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism for TSHβ expression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on laser-captured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of the KA2, which is an ionotropic glutamic acid receptor (iGluR). In addition, the amino acid transporter A2 (ATA2), also known as the glutamine transporter, and glutaminase (GLS), as well as GLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid on TSHβ expression and αGSU expression in PT slice cultures. l-Glutamine and l-glutamic acid significantly stimulated TSHβ expression in PT slices after 2- and 4-h treatments, and the effect of l-glutamic acid was stronger than that of l-glutamine. In contrast, treatment with glutamine and glutamic acid did not affect αGSU expression in the PT or the expression of TSHβ or αGSU in the PD. These results strongly suggest that glutamine is taken up by PT cells through ATA2 and that glutamic acid locally converted from glutamine by Gls induces TSHβ expression via the KA2 in an autocrine and/or paracrine manner in the PT.

  14. Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels

    Science.gov (United States)

    Skoczyńska, Anna; Wojakowska, Anna; Turczyn, Barbara; Zatońska, Katarzyna; Wołyniec, Maria; Rogala, Natalia; Szuba, Andrzej; Bednarek-Tupikowska, Grażyna

    2016-01-01

    Background Plasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism. Material/Methods The selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates. Results Serum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=−0.21; p<0.01) and between TSH and PLTP (r=−0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=−0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=−0.24; p<0.001) has been demonstrated as well. Conclusions The decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism. PMID:27899788

  15. The association between soya consumption and serum thyroid-stimulating hormone concentrations in the Adventist Health Study-2.

    Science.gov (United States)

    Tonstad, Serena; Jaceldo-Siegl, Karen; Messina, Mark; Haddad, Ella; Fraser, Gary E

    2016-06-01

    Consumers may choose soya foods as healthful alternatives to animal products, but concern has arisen that eating large amounts of soya may adversely affect thyroid function. The present study aimed to examine the association between soya food consumption and serum thyroid-stimulating hormone (TSH) concentrations in North American churchgoers belonging to the Seventh-day Adventist denomination that encourages vegetarianism. Participants completed six repeated 24 h dietary recalls within a 6-month period. Soya protein and soya isoflavone intakes were estimated, and their relationships to TSH concentrations measured at the end of 6 months were calculated using logistic regression analyses. Calibration sub-study of the Adventist Health Study-2. Women (n 548) and men (n 295) who were not taking thyroid medications. In men, age and urinary iodine concentrations were associated with high serum TSH concentrations (>5 mIU/l), while among women White ethnicity was associated with high TSH. In multivariate models adjusted for age, ethnicity and urinary iodine, soya isoflavone and protein intakes were not associated with high TSH in men. In women higher soya isoflavone consumption was associated with higher TSH, with an adjusted odds ratio (highest v. lowest quintile) of 4·17 (95 % CI 1·73, 10·06). Likewise, women with high consumption of soya protein (midpoint of highest quintile, 11 g/d) v. low consumption (midpoint of lowest quintile, 0 g/d) carried increased odds of high TSH (OR=2·69; 95 % CI 1·34, 5·30). In women high consumption of soya was associated with elevated TSH concentrations. No associations between soya intake and TSH were found in men.

  16. An electrochemiluminescence immunosensor for thyroid stimulating hormone based on polyamidoamine-norfloxacin functionalized Pd-Au core-shell hexoctahedrons as signal enhancers.

    Science.gov (United States)

    Liu, Yuting; Zhang, Qiqi; Wang, Haijun; Yuan, Yali; Chai, Yaqin; Yuan, Ruo

    2015-09-15

    In this work, a novel polyamidoamine-norfloxacin (PAMAM-NFLX) complex and core-shell Pd-Au hexoctahedrons (Pd@Au HOHs) as enhancers are employed for development of a sensitive sandwich-type electrochemiluminescence (ECL) immunosensor to detect thyroid stimulating hormone (TSH). Here, norfloxacin (NFLX) is decorated abundantly on the surface of polyamidoamine (PAMAM) dendrimer via amide linkage to form PAMAM-NFLX complex. Thus, the resultant PAMAM-NFLX can serve as a novel co-reactant to efficiently amplify the ECL signal of peroxydisulfate-oxygen (S2O8(2-)-O2) system. Pd@Au HOHs were used as nano-carriers to assemble detection antibody (Ab2) and the PAMAM-NFLX complex. Besides, it can further enhance the ECL signal by promoting the generation of intermediate free radical HO(•) during the ECL reaction of S2O8(2-)-O2 system. The proposed immunosensor shows high sensitivity and specificity, and responds linearly to the concentration of TSH from 0.05 to 20 μIU mL(-1) with a low detection limit of 0.02 μIU mL(-1) (S/N=3). Moreover, the immunosensor successfully achieves the detection of TSH in practical human blood serum with desirable results. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Molecular cloning, genomic organization, and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to members of the thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone/choriogonadotropin receptor family from mammals

    DEFF Research Database (Denmark)

    Hauser, F; Nothacker, H P; Grimmelikhuijzen, C J

    1997-01-01

    Using oligonucleotide probes derived from consensus sequences for glycoprotein hormone receptors, we have cloned an 831-amino acid residue-long receptor from Drosophila melanogaster that shows a striking structural homology with members of the glycoprotein hormone (thyroid-stimulating hormone (TSH...... until after pupation. Adult male flies express high levels of receptor mRNA, but female flies express about 6 times less. The expression pattern in embryos and larvae suggests that the receptor is involved in insect development. This is the first report on the molecular cloning of a glycoprotein hormone...

  18. Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males

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    Qingqing Zhang

    2014-01-01

    Full Text Available Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OHD] is associated with low circulating thyroid-stimulating hormone (TSH levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41–78 years, were enrolled in this cross-sectional study. Serum levels of 25(OHD, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OHD levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s, and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.

  19. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

    Science.gov (United States)

    Svendstrup, Mathilde; Ohrt, Johanne Dam; Dahl, Maria; Fonvig, Cilius Esmann; Hollensted, Mette; Have, Christian Theil; Kadarmideen, Haja N.; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian; Grarup, Niels

    2017-01-01

    Background Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively. Objective This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity. Methods Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5−24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2−22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses. Results No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 ∙ 10−16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 ∙ 10−20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 ∙ 10−11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 ∙ 10−10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (padolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH concentrations in children, suggesting comparable genetic determinants of thyroid function in adults and children. PMID:28333968

  20. Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

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    Seo Young Sohn

    2015-09-01

    Full Text Available BackgroundThere are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT preparation method on changes of weight, comparing thyroid hormone withdrawal (THW and recombinant human TSH (rhTSH.MethodsWe retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4 replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI at baseline and follow-up.ResultsSignificant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods.ConclusionFemale DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT.

  1. Effect of a long-acting somatostatin analogue (SMS 201-995 on a growth hormone and thyroid stimulating hormone-producing pituitary tumor.

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    Hirasawa,Ryoto

    1991-04-01

    Full Text Available A 46-year-old woman with acromegaly and hyperthyroidism due to a pituitary adenoma. She had high serum thyroid-stimulating hormone (TSH levels and very high serum growth hormone (GH levels. Transsphenoidal removal of the tumor, post-operative irradiation, frontal craniotomy for removal of residual tumor and large-dose bromocriptine therapy were carried out consecutively. After therapy, serum GH levels gradually decreased, but not to the normal range, and serum TSH levels remained at inappropriately normal levels. Using immunoperoxidase techniques, GH-, TSH- and follicle-stimulating hormone (FSH-containing cells were demonstrated in the adenoma. A long-acting somatostatin analogue (SMS 201-995, 600 micrograms/day suppressed the serum GH level to the normal range with a concomitant suppression of TSH. Furthermore, the paradoxical serum GH responses to TRH and LH-RH were slightly improved. No important subjective side-effects were noted. Therefore, SMS 201-995 appeared to be a very effective drug in this patient with a GH- and TSH-producing pituitary tumor.

  2. Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults. The importance of environmental factors, including thyroid antibodies

    DEFF Research Database (Denmark)

    Jensen, Esther; Hyltoft Petersen, Per; Blaabjerg, Ole

    2004-01-01

    It has previously been shown that thyroid antibodies affect thyroid stimulating hormone (TSH) concentrations in men and women and that TSH levels are predictive of future thyroid disease. We investigated the validity of the National Academy of Clinical Biochemistry (NACB) guidelines regarding......-plots. Consequently, a common reference interval for serum TSH of 0.58-4.07 mlU/l for all adults between 17 and 66 years of age was established. This reference interval is much higher than expected from the NACB-guidelines....

  3. Thyroid stimulating hormone suppression post-therapy in patients with Graves' disease: a systematic review of pathophysiology and clinical data.

    Science.gov (United States)

    Yu, Huan; Farahani, Pendar

    2015-04-08

    Post-treatment hypothyroidism is common in Graves' disease, and clinical guidelines recommend monitoring for it; however, thyroid stimulating hormone (TSH) can remain suppressed in these patients following treatment. The objectives of this study were to explore the proposed pathophysiology behind the phenomenon of post-therapy TSH suppression and to systematically review existing clinical data on post-therapy TSH suppression in patients with Graves' disease. A systematic literature search was performed using EMBASE and PubMed databases, with several combinations of MeSH terms. Bibliography mining was also done on relevant articles to be as inclusive as possible. A total of 18 articles described possible mechanisms for post-therapy TSH suppression. Several of the studies demonstrate evidence of thyrotroph atrophy and hypothesize that this contributes to the ongoing suppression. TSH receptors have been identified in folliculo-stellate cells of the pituitary as well as astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies have demonstrated inverse correlation between autoantibody titres and TSH levels, suggestive of their role in mediating ongoing TSH suppression in patients with Graves' disease. In addition, five studies were identified that provided clinical data on the duration of TSH suppression. Combined data show that 45.5% of patients recover TSH by 3 months after treatment, increasing to 69.3% by 6 months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows that for patients who are TBII negative, 80.7% recover their TSH by 6 months compared with only 58.7% in those who are TBII positive (p= 0.003). Clinical data suggests that TSH recovery is most likely to occur within the first 6 months after treatment, with recovery plateauing at approximately 70% of patients, suggesting that reliance on this assay for monitoring can be very misleading. Furthermore, TBII positivity is associated with lower likelihood of TSH

  4. Immunodetection of Luteinizing Hormone (LH, Follicle-Stimulating Hormone (FSH, Thyroid Stimulating Hormone (TSH and Prolactin (PRL in Brachionus calyciflorus (Rotifera: Monogononta

    Directory of Open Access Journals (Sweden)

    Jesús Alvarado-Flores

    2009-12-01

    Full Text Available The endocrine system controls and coordinates behavioral, biochemical, and physiological processes through signal mechanisms using neuropeptides or products of neurosecretory cells. Among invertebrates, this system is poorly studied in rotifers, in which estrogens and androgens significantly affect sexual reproduction. This is the first report of the presence of the Luteinizing Hormone (LH, Follicle-Stimulating Hormone (FSH, Thyroid Stimulating Hormone (TSH and Prolactin (PRL in rotifers. Analyses included the avidin-biotin-peroxidase complex method with primary antibodies LH (Anti-Rat LH serum for RIA, PRL (Anti-Rat PRL serum for RIA, FSH (Anti-Rat FSH serum for RIA and TSH (Anti-Rat TSH serum for RIA. These hormones were found in females, males and parthenogenetic and sexual eggs of the freshwater Brachionus calyciflorus. The immunoreactivity of FSH, LH, TSH and PRL in females was observed in: ovaries, cerebrum, mastax, stomach, lorica, and the stomach gland. However, in males LH was observed only at the trochal disk and cerebrum. The hormones FSH, TSH and PRL, were observed in testicles, contractil vesicles, and cementary gland of males. Regarding amictic or parthenogenetic eggs, the hormones LH, FSH, TSH, and PRL were located mainly in the micromeres, and the staining in the macromeres was weak. On the other hand, in the mictic or sexual eggs the inner shell is stained for the hormones PRL and LH, opposite to the staining of FSH and TSH, located mainly in the embryo. In general, immuno-reactivity was observed in areas important for the reproductive, excretory, digestive and developmental processes. Rev. Biol. Trop. 57 (4: 1049-1058. Epub 2009 December 01.Se logró detectar la presencia de las hormonas: Hormona Luteinizante (LH, Hormona Folículo Estimulante (FSH, Hormona Estimulante de la Tiroides (TSH y Prolactina (PRL en Brachionus calyciflorus siendo el primer reporte de la presencia de dichas hormonas en rotíferos. Estas hormonas fueron

  5. Roles of thyroid-stimulating hormone in tissues other than the thyroid%促甲状腺激素的甲状腺外作用

    Institute of Scientific and Technical Information of China (English)

    田利民; 高聆; 赵家军

    2010-01-01

    In recent years thyroid-stimulating hormone receptor (TSHR) has been identified in a number of tissues other than thyroid, including brain, testes, kidney, heart, bone, thymus, lymphocytes, adipose tissue, fibroblasts and liver cells. This suggests that thyroid-stimulating hormone (TSH) may has a wider functional role than traditional recognition. Here mainly enumerates some important roles of TSH in adipose tissue,bone and liver.%近年来研究证明,促甲状腺激素受体(TSHR)存在于大脑、睾丸、肾脏、心肌、骨骼、胸腺、淋巴细胞、脂肪组织、纤维母细胞和肝细胞等多种甲状腺外组织和细胞上.促甲状腺激素(TSH)可能通过TSHR介导发挥着广泛的、非传统认识的功能作用.现主要列举了TSH在脂肪组织、骨骼和肝脏中的一些重要作用.

  6. Hypothalamic regulation of thyroid-stimulating hormone and prolactin release : the role of thyrotrophin-releasing hormone

    NARCIS (Netherlands)

    G.A.C. van Haasteren (Goedele)

    1995-01-01

    textabstractThyrotrophin-releasing-hormone (TRH), a tripeptide, is produced by hypothalamic neurons and transported along their axons to the median eminence (ME). From there it is released at nerve terminals into hypophyseal portal blood. It is then transported to the anterior pituitary gland where

  7. A STUDY ON ESTIMATION OF SERUM CALCIUM IN SUBCLINICAL HYPOTHYROID FEMALES OF DIFFERENT AGE GROUPS AND ITS CORRELATION WITH THYROID STIMULATING HORMONE (TSH

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    M. Kaleemullah Khan

    2016-09-01

    Full Text Available BACKGROUND Hypothyroidism is a clinical condition arising because of the inadequacy of thyroid hormones or from inability to perform a normal function. Hypothyroidism is a typical metabolic condition in almost all community groups. In India, 42 million individuals are experiencing thyroid disease; hypothyroidism being the commonest thyroid disorder.(1 Serum calcium levels are lower in patients with high TSH than with typical TSH (p <0.01.(2 METHODOLOGY There were 50 females with SCH were selected in the study. Patients with 18 to 65 years of age, with TSH levels more than 5.0 mIU/L, free T4 within normal limits, and general well-being patients were incorporated. The study period was from January to April 2016. Owaisi Hospital and Research Centre, it is a 1000 bedded hospital with super specialty services in Hyderabad, giving particularly tertiary level human services to all strata of individuals. RESULTS Out of 50 patients, 24 patients with hypothyroidism are in hypocalcaemia, which constitute 48% (n=24 of the people required in the study had estimation of serum calcium under 9 mg/dL. This shows to be the one of the important concern associated with hypothyroidism. In rest 52% (n=26 of patients who were having normal calcium levels, chances of developing hypocalcaemia in future is high. DISCUSSION The mean age, serum calcium and thyroid stimulating hormone (TSH in AlaEldin S. Ashmaik et al was: Age: 32.00±15.76, TSH: 26.02±34.74, and serum calcium: 7.97±.62 while in our study it shows a mean age of 39.9 ±13.82, TSH: 10.47 ±3.46, and serum calcium: 9.04 ±1.47. The mean age in our study was higher than the study by AlaEldin done in Sudan population, the mean TSH was found to be much lower while the serum calcium levels show elevated levels in our study in contrast to study by AlaEldin S. Ashmaik et al. CONCLUSION This study presumed that in Telangana state, patients have low levels of serum calcium in hypothyroidism. S.Ca++ in hypothyroid

  8. 血清促甲状腺激素与代谢综合征关系的研究进展%The research progress of relationship between serum thyroid stimulating hormone and the metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    梁文芳; 兰丽珍

    2015-01-01

    Metabolic syndrome (MS) is a series of metabolic disorder syndrome relating to insulin resistance, which is a risk factor for atherosclerosis and vascular disease. It includes central obesity, lipid metabolism disorders, high blood pressure, high blood sugar and glucose tolerance. Studies have shown that the human's hypothalamus, kidneys, liver and adipose tissue can express functional thyroid stimulating hormone receptor (TSHR) besides thyroid tissue. Thyroid stimulating hormone(TSH) bind to these receptors, involving in the regulation of blood sugar, blood lipids, blood pressure and the formation of fat through multiple targets and signal pathways.%代谢综合征(metabolic syndrome,MS)是指一系列与胰岛素抵抗相关的引起动脉粥样硬化和血管疾病的危险因素的代谢紊乱症候群,其特征包括中心性肥胖、脂代谢紊乱、高血压、高血糖或糖耐量减低. 研究发现,人类下丘脑、肾脏、肝脏、脂肪组织等多种甲状腺外组织表达功能性的促甲状腺激素受体(TSHR),促甲状腺激素(TSH)作用于这些受体,可能通过多个靶点及信号通路参与体内血糖、血脂、血压等的调节及肥胖的形成.

  9. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

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    Olympia Anastasiou

    Full Text Available Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS, have been described in many diseases. However, the relationship between acute liver failure (ALF and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR. TSH, free thyroxine (fT4, free triiodothyronine (fT3, T4, and T3 were determined.More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

  10. Atrial fibrillation associated with a thyroid stimulating hormone-secreting adenoma of the pituitary gland leading to a presentation of acute cardiac decompensation: A case report

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    George Jyothis T

    2008-02-01

    Full Text Available Abstract Introduction Hyperthyroidism is a well established cause of atrial fibrillation (AF. Thyroid Stimulating Hormone-secreting pituitary tumours are rare causes of pituitary hyperthyroidism. Whilst pituitary causes of hyperthyroidism are much less common than primary thyroid pathology, establishing a clear aetiology is critical in minimising complications and providing appropriate treatment. Measuring Thyroid Stimulating Hormone (TSH alone to screen for hyperthyroidism may be insufficient to appropriately evaluate the thyroid status in such cases. Case presentation A 63-year-old Caucasian man, previously fit and well, presented with a five-day history of shortness of breath associated with wheeze and dry cough. He denied symptoms of hyperthyroidism and his family, social and past history were unremarkable. Initial investigation was in keeping with a diagnosis of atrial fibrillation (AF with fast ventricular response leading to cardiac decompensation. TSH 6.2 (Normal Range = 0.40 – 4.00 mU/L, Free T3 of 12.5 (4.00 – 6.8 pmol/L and Free T4 51(10–30 pmol/L. Heterophilic antibodies were ruled out. Testosterone was elevated at 43.10 (Normal range: 10.00 – 31.00 nmol/L with an elevated FSH, 18.1 (1.0–7.0 U/L and elevated LH, 12.4 (1.0–8.0 U/L. Growth Hormone, IGF-1 and prolactin were normal. MRI showed a 2.4 cm pituitary macroadenoma. Visual field tests showed a right inferotemporal defect. While awaiting neurosurgical removal of the tumour, the patient was commenced on antithyroid medication (carbimazole and maintained on this until successful trans-sphenoidal excision of the macroadenoma had been performed. AF persisted post-operatively, but was electrically cardioverted subsequently and he remains in sinus rhythm at twelve months follow-up off all treatment. Conclusion This case reiterates the need to evaluate thyroid function in all patients presenting with atrial fibrillation. TSH-secreting pituitary adenomas must be considered

  11. 血清促甲状腺素在甲状腺微小癌中的表达及临床价值分析%The expression and clinical value of serum thyroid stimulating hormone in thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    赵磊; 李志军; 艾杨卿

    2016-01-01

    Objective:To research the expression and clinical value of serum thyroid stimulating hormone in thyroid cancer. Methods:260 patients with thyroid nodules were selected,statistical analysis of serum thyroid stimulating hormone test,operation record,etc..Results:The concentration of serum thyroid stimulating hormone was lower than that of differentiated thyroid carcinoma(P<0.05).Conclusion:Because there is no significant difference between the serum thyroid stimulating hormone concentrations and benign thyroid cancer patients,it can not be used as a predictive indicator of thyroid cancer risk.%目的:研究血清促甲状腺激素在甲状腺微小癌中的表达以及临床上的诊断价值.方法:收治甲状腺结节患者260例,对患者手术前的血清促甲状腺激素检查、手术记录等进行统计、分析.结果:甲状腺良性结节患者血清促甲状腺激素的浓度低于分化型甲状腺癌(P<0.05).结论:由于甲状腺微小癌患者的血清促甲状腺激素浓度与良性之间的差异没有统计学意义,还不能作为甲状腺微小癌的风险评估预测指标.

  12. An innovative sample-to-answer polymer lab-on-a-chip with on-chip reservoirs for the POCT of thyroid stimulating hormone (TSH).

    Science.gov (United States)

    Jung, Wooseok; Han, Jungyoup; Kai, Junhai; Lim, Ji-Youn; Sul, Donggeun; Ahn, Chong H

    2013-12-07

    A new sample-to-answer polymer lab-on-a-chip, which can perform immunoassay with minimum user intervention through on-chip reservoirs for reagents and single-channel assay system, has been designed, developed and successfully characterized as a point-of-care testing (POCT) cartridge for the detection of thyroid stimulating hormone (TSH). Test results were obtained within 30 minutes after a sample was dropped into the POCT cartridge. The analyzed results of TSH showed a linear range of up to 55 μIU mL(-1) with the limit of detection (LOD) of 1.9 μIU mL(-1) at the signal-to-noise ratio (SNR) of 3. The reagents stored in the on-chip reservoirs maintained more than 97% of their initial volume for 120 days of storage time while the detection antibody retained its activity above 98% for 120 days. The sample-to-answer polymer lab-on-a-chip developed in this work using the mass-producible and low-cost polymer is well suited for the point-of-care testing of rapid in vitro diagnostics (IVD) of TSH.

  13. The upper limit of the reference range for thyroid-stimulating hormone should not be confused with a cut-off to define subclinical hypothyroidism.

    Science.gov (United States)

    Waise, Ahmed; Price, Hermione C

    2009-03-01

    The upper limit of the reference range for serum thyroid-stimulating hormone (TSH) is used to assist in identifying individuals with hypothyroidism. Improvements in TSH assays have led to better definition of the lower limit of the reference range, but the upper limit of the range for a healthy population is currently a topic of some debate. Population studies have improved our understanding of the clinical implications of elevated serum TSH concentrations in terms of future progression to hypothyroidism, but have not yet fully elucidated the correlation of modestly elevated TSH levels with long-term morbidity. This paper will review the current debate including the arguments for and against reducing the upper limit of the TSH range, whether such a level should be based on evidence from epidemiological studies, and the implications of categorizing large numbers of people with subclinical hypothyroidism. The impact of using different methodologies for the measurement of TSH and the inherent variability of results on reference ranges is also discussed. We argue that the reference range for TSH should be assay-specific and be determined by standard techniques in normal populations as recommended by the National Academy of Clinical Biochemistry. In contrast, we suggest that a decision level be determined separately from epidemiological studies to identify a population with subclinical hypothyroidism. Serial monitoring of TSH in this population deserves further study as a means of identifying those at risk of progressing to frank hypothyroidism and meriting treatment.

  14. Propylthiouracil, Perchlorate, and Thyroid-Stimulating Hormone Modulate High Concentrations of Iodide Instigated Mitochondrial Superoxide Production in the Thyroids of Metallothionein I/II Knockout Mice

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    Qi Duan

    2016-03-01

    Full Text Available BackgroundIncreased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thyroid disease. Metallothioneins (MTs are regarded as scavengers of reactive oxygen species (ROS in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU, a thyroid peroxidase inhibitor, perchlorate (KClO4, a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH on mitochondrial superoxide production instigated by high concentrations of iodide in the thyroids of MT-I/II knockout (MT-I/II KO mice.MethodsEight-week-old 129S7/SvEvBrd-Mt1tm1Bri Mt2tm1Bri/J (MT-I/II KO mice and background-matched wild type (WT mice were used.ResultsBy using a mitochondrial superoxide indicator (MitoSOX Red, lactate dehydrogenase (LDH release, and methyl thiazolyl tetrazolium (MTT assay, we demonstrated that the decreased relative viability and increased LDH release and mitochondrial superoxide production induced by potassium iodide (100 µM can be relieved by 300 µM PTU, 30 µM KClO4, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05. Compared to the WT mice, a significant decrease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were detected in MT-I/II KO mice(P<0.05.ConclusionWe concluded that PTU, KClO4, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of iodide-induced mitochondrial superoxide production in the thyroid.

  15. Clinical Evaluation of the Immune Colloidal Gold Method for Rapid Qualitative and Quantitative Measurement of Thyroid-Stimulating Hormone as an Assay for Hypothyroidism.

    Science.gov (United States)

    Wang, Tingting; Sheng, Shiwei; Ruan, Meifang; Yan, Jing; Gu, Jianying; Jiang, Yumin; Gao, Yunchao; Lu, Hankui

    2016-11-01

    The immune colloidal gold (ICG) method of measuring thyroid-stimulating hormone (TSH) is a rapid and easy-to-perform test, allowing off-site measurements. This study compared the clinical utility of the first ICG-based qualitative and quantitative TSH test methods in China with the third-generation serum TSH assay used worldwide. Fingertip and venous blood was collected within 30 min from 283 patients initially suspected of hypothyroidism. TSH was measured in fingertip blood using ICG-based qualitative quantitative tests. Serum TSH in venous blood was tested using the third-generation serum TSH assay. Correlations between systems were tested by kappa or Spearman correlation coefficients. Compared with the third-generation serum TSH assay, the ICG-qualitative TSH test kit had a kappa coefficient of 0.86, a sensitivity of 85.00%, and a specificity of 99.38% in screening for hypothyroidism. The percentages of false negatives and false positives among all subjects were 6.38% and 0.35% respectively; the total consistency rate of the two methods was 93.26%. When compared with the third-generation serum TSH assay, the ICG-quantitative TSH analysis system had a Spearman correlation coefficient of 0.91, a sensitivity of 88.43%, and a specificity of 98.77%. The percentages of false negatives and false positives among all subjects were 4.95% and 0.71%, respectively; the total consistency rate of the two methods was 94.35%. Both ICG-based assays are easier and faster to perform than the third-generation, laboratory-based serum TSH assay method. The ICG-based methods showed acceptable performance in the simplified screening for hypothyroidism. ClinicalTrials.gov identifier, NCT01921452. Merck Serono Co., Ltd.

  16. The association between serum thyroid stimulating hormone and thyroid cancer%血清促甲状腺激素与甲状腺癌的关系

    Institute of Scientific and Technical Information of China (English)

    闫慧娴; 谷伟军; 吕朝晖

    2013-01-01

    More and more evidence showed that serum thyroid stimulating hormone(TSH) was an independent predictor for the diagnosis of thyroid cancer in patients with thyroid nodular goiter.In patients with thyroid nodular goiter,the risk of thyroid cancer increases with serum TSH level,and even TSH level within normal ranges,higher TSH level is associated with a higher frequency and more advanced stage of thyroid cancer.TSH suppression therapy can reduce thyroid carcinoma-related mortality and recurrence rate in high risk patients.TSH plays a key role in the development of thyroid cancer.%越来越多的证据显示,血清促甲状腺激素(TSH)是预测结节性甲状腺肿患者发生甲状腺癌的独立危险因素.即使血清TSH水平在正常范围内,结节性甲状腺肿患者发生甲状腺癌的风险也随着血清TSH水平的升高而逐渐增加.高水平的TSH与甲状腺癌的高发生率以及晚期甲状腺癌关系密切.血清TSH抑制治疗能降低肿瘤进展高危患者的复发率和死亡率.血清TSH在甲状腺癌的发展过程中起着非常重要的作用.

  17. Serum thyroid-stimulating hormone and anti-thyroglobulin antibody are independently associated with lesions in spinal cord in central nervous system demyelinating diseases.

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    Youming Long

    Full Text Available Transverse myelitis (TM is associated with neuromyelitis optica (NMO and multiple sclerosis (MS. Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115 of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105. The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH, anti-thyroglobulin antibodies (TG-Ab, and antithyroid peroxidase antibody (TPO-Ab than MS patients (p<0.05. The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05. In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52 without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01. Patients positive for aquaporin-4 (AQP4 antibodies showed higher abnormalities of TSH (p = 0.001, TG-Ab (p = 0.004 and TPO-Ab (p<0.0001 levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR]  = 33.994; p<0.0001, TG-Ab (OR = 7.703; p = 0.017 and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001. This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.

  18. Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial

    Science.gov (United States)

    Karimifar, Mozhgan; Aminorroaya, Ashraf; Amini, Masoud; Mirfendereski, Taghi; Iraj, Bijan; Feizi, Awat; Norozi, Atsa

    2014-01-01

    Background: The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people. Materials and Methods: In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study. Results: Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml) and high-normal (2.6-5.5 μU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01). Conclusion: In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume. PMID:25657744

  19. Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial

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    Mozhgan Karimifar

    2014-01-01

    Full Text Available Background: The people with prediabetes have insulin resistance (IR. IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people. Materials and Methods: In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43 and placebo (n = 46 treated groups. Serum thyroid stimulating hormone (TSH was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study. Results: Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml and high-normal (2.6-5.5 μU/ml ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01. Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03. In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01. Conclusion: In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume.

  20. Constitutive activation of the thyroid-stimulating hormone receptor (TSHR by mutating Ile691 in the cytoplasmic tail segment.

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    Zheng Liu

    Full Text Available BACKGROUND: Autosomal dominant non-autoimmune hyperthyroidism (ADNAH is a rare genetic disorder of the endocrine system. Molecular genetic studies in ADNAH have revealed heterozygous germline mutations in the TSHR. To data, mutations leading to an increase in the constitutive activation of the TSHR have been described in the transmembrane segments, exoloops and cytoplasmic loop of TSHR. These mutations result in constitutive activation of the G(αs/cAMP or G(αq/11/inositol phosphate (IP pathways, which stimulate thyroid hormone production and thyroid proliferation. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study, we reported a new TSHR mutation located in the C-terminal domain of TSHR, which results in a substitution of the conserved Ile(691 for Phe. In this study, to address the question of whether the I691F mutated receptor could be responsible for G(αs/cAMP or G(αq/11/IP constitutive activity, wild-type and TSHR mutants were expressed in COS-7 cells to determine cAMP constitutive activity and IP formation. Compared to the cell surface with expression of the A623V mutated receptor as positive control, the I691F mutated receptor showed a slight increase of cAMP accumulation. Furthermore, I691F resulted in constitutive activation of the G(αq/11/IP signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results indicate that Ile(691 not only contributes to keeping TSHR inactive in the G(αs/cAMP pathways but also in the G(αq/11/IP cascade.

  1. The effect of thyroid stimulating hormone suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma.

    Science.gov (United States)

    Moon, Jae Hoon; Jung, Kyong Yeun; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul

    2016-02-01

    Subclinical hyperthyroidism has been reported to increase the fracture risk. However, the effect of thyroid stimulating hormone (TSH) suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma (DTC) is still unclear. The aim of this study was to investigate the effect of TSH suppression on bone geometry in the hip area of pre- and postmenopausal women with DTC. We conducted a retrospective cohort study including 99 women with DTC (25 pre- and 74 postmenopausal) who had received TSH suppressive therapy for at least 3years and 297 control subjects (75 and 222, respectively) matched for sex and age. Bone mineral density (BMD) in the spine and hip area and bone geometry at the femoral neck measured by dual energy X-ray absorptiometry (DXA) were compared between patients and controls. The association between thyroid hormone and bone parameters was investigated. All analyses of bone parameters were adjusted for age, body mass index, and serum calcium levels. In premenopausal subjects, TSH suppressive therapy was not associated with poor bone parameters. In postmenopausal subjects, patients with DTC undergoing TSH suppression showed lower cross-sectional moment of inertia (CSMI), cross-sectional area, and section modulus and thinner cortical thickness at the femoral neck than those of control subjects, whereas their femoral neck BMD was comparable with controls. Total hip BMD was lower in postmenopausal patients than in controls. CSMI and section modulus at the femoral neck were independently associated with serum free T4 levels in postmenopausal patients. The difference in femoral neck bone geometry between patients and controls was only apparent in postmenopausal DTC patients with free T4 >1.79ng/dL (23.04pmol/l), and not in those with free T4 levels ≤1.79ng/dL (23.04pmol/l). TSH suppression in postmenopausal DTC patients was associated with decreased bone strength by altering bone geometry rather than BMD in the hip area

  2. Ovine thyroid stimulating hormone (TSH) heterologously stimulates production of thyroid hormones from Chinese soft-shell turtle (Pelodiscus sinensis) and bullfrog (Rana catesbeiana and Rana rugulosa) thyroids in vitro.

    Science.gov (United States)

    Huang, Wei-Tung; Chien, Jung-Tsun; Weng, Ching-Feng; Jeng, Yung-Yue; Lu, Li-Chia; Yu, John Yuh-Lin

    2009-06-01

    Thyroid hormones are important for regulating a variety of developmental processes in vertebrates, including growth, differentiation, metamorphosis, and oxidative metabolism. In particular, this study focused on the in vitro production of thyroxine (T(4)) and triiodothyronine (T(3)) from thyroids in American bullfrogs (Rana catesbeiana), Chinese bullfrogs (Rana rugulosa Wiegmann), and Chinese soft-shell turtles (Pelodiscus sinensis) treated with ovine thyroid stimulating hormone (TSH) at different culture intervals (2, 4, 8, and 12 h) and dosages (1, 10, 50 or 100 ng). The levels of T(4) and T(3) in the tested animals were elevated upon stimulation in a time- and dose-dependent manner, indicating de novo synthesis of T(4) and T(3). Significantly higher hormone levels were observed in the Chinese bullfrog compared to the other two species, for both the time-course and dose-response experiments. Although the bullfrog secreted significantly higher levels of T(4) and T(3), a higher T(4)-conversion capacity was found in the Chinese soft-shell turtle. The highest ratios of T(3) to T(4) were observed in the American bullfrog and Chinese soft-shell turtle for the time-course and dose-response experiments, respectively. These findings suggest that the Chinese soft-shell turtle and bullfrog thyroids can accept ovine TSH for T(4)- and T(3)-formation in a time- and dose-dependent manner, supporting the hypothesis that the binding interactions between TSHs and thyroidal receptors are conserved in vertebrates.

  3. Study of thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in subjects with dental fluorosis.

    Science.gov (United States)

    Hosur, Mahadevi B; Puranik, R S; Vanaki, Shrinivas; Puranik, Surekha R

    2012-04-01

    Apart from its well-known deleterious dental and skeletal effects, fluoride excess can have toxic effects on many other tissues. Fluoride, when in excess, is known to interfere with thyroid gland function. Fluoride-induced thyroid disturbances similar to those observed in iodine deficiency state in spite of adequate iodine intake have been documented. Similar thyroid disturbances in individuals with dental fluorosis have not been well studied in populations with endemic fluorosis. This work was undertaken to study the effects of fluoride-induced thyroid disturbances in individuals with dental fluorosis. The study group included 65 subjects with dental fluorosis from endemic fluorosis populations. An additional control group was comprised of 10 subjects without dental fluorosis. The drinking water fluoride levels of the study populations were analyzed. Serum free FT3, FT4, and TSH levels of both groups were assessed. All subjects with dental fluorosis had serum levels of thyroid hormones (FT3, FT4, and TSH) within the normal range, with the exception of 1 individual, who had elevated levels of TSH. Statistical significance was found when FT3 and TSH values were compared with different Dean's index groups by a 1-way ANOVA test: FT3 (F = 3.4572; P=.0377) and TSH (F = 3.2649 and P=.0449). Findings of this study did not show any significant alterations in the levels of the thyroid hormones FT3, FT4, and TSH in subjects with dental fluorosis. Our observations suggest that thyroid hormone levels were not altered in subjects with dental fluorosis. Hence, future studies of this kind, along with more detailed investigations are needed.

  4. Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

    Science.gov (United States)

    Matsumoto, Tadashi; Miyakoshi, Kei; Saisho, Yoshifumi; Ishii, Tomohiro; Ikenoue, Satoru; Kasuga, Yoshifumi; Kadohira, Ikuko; Sato, Seiji; Momotani, Naoko; Minegishi, Kazuhiro; Yoshimura, Yasunori

    2013-01-01

    High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

  5. Molecular cloning and sequence analysis of a cDNA encoding pituitary thyroid stimulating hormone beta-subunit of the Chinese soft-shell turtle Pelodiscus sinensis and regulation of its gene expression.

    Science.gov (United States)

    Chien, Jung-Tsun; Chowdhury, Indrajit; Lin, Yao-Sung; Liao, Ching-Fong; Shen, San-Tai; Yu, John Yuh-Lin

    2006-04-01

    A cDNA encoding thyroid stimulating hormone beta-subunit (TSHbeta) was cloned from pituitary of the Chinese soft-shell turtle, Pelodiscus sinensis, and its regulation of mRNA expression was investigated for the first time in reptile. The Chinese soft-shell turtle TSHbeta cDNA was cloned from pituitary RNA by reverse transcription and polymerase chain reaction (RT-PCR), and rapid amplification cDNA end (RACE) methods. The Chinese soft-shell turtle TSHbeta cDNA consists of 580-bp nucleotides, including 67-bp nucleotides of 5'-untranslated region (UTR), 402-bp of the open reading frame, and 97-bp of 3'-UTR followed by a 14 poly (A) trait. It encodes a precursor protein molecule of 133 amino acids with a putative signal peptide of 19 amino acids and a putative mature protein of 114 amino acids. The number and position of 12 cysteine residues, presumably forming six disulfide bonds, one putative asparagine-linked glycosylation site, and six proline residues that are found at positions for changing the backbone direction of the protein have been conserved in the turtle as in other vertebrate groups. The deduced amino acid sequence of the Chinese soft-shell turtle TSHbeta mature protein shares identities of 82-83% with birds, 71-72% with mammals, 49-57% with amphibians, and 44-61% with fish. The Chinese soft-shell turtle pituitaries were incubated in vitro with synthetic TRH (TSH-releasing hormone), thyroxine and triiodothyronine at doses of 10(-10) and 10(-8)M. TRH stimulated, while thyroid hormones suppressed, TSHbeta mRNA levels in dose-related manner. The sequences of cDNA and its deduced peptide of TSHbeta as well as the regulation of its mRNA level were reported for the first time in reptile.

  6. Analytical Bias Exceeding Desirable Quality Goal in 4 out of 5 Common Immunoassays: Results of a Native Single Serum Sample External Quality Assessment Program for Cobalamin, Folate, Ferritin, Thyroid-Stimulating Hormone, and Free T4 Analyses.

    Science.gov (United States)

    Kristensen, Gunn B B; Rustad, Pål; Berg, Jens P; Aakre, Kristin M

    2016-09-01

    We undertook this study to evaluate method differences for 5 components analyzed by immunoassays, to explore whether the use of method-dependent reference intervals may compensate for method differences, and to investigate commutability of external quality assessment (EQA) materials. Twenty fresh native single serum samples, a fresh native serum pool, Nordic Federation of Clinical Chemistry Reference Serum X (serum X) (serum pool), and 2 EQA materials were sent to 38 laboratories for measurement of cobalamin, folate, ferritin, free T4, and thyroid-stimulating hormone (TSH) by 5 different measurement procedures [Roche Cobas (n = 15), Roche Modular (n = 4), Abbott Architect (n = 8), Beckman Coulter Unicel (n = 2), and Siemens ADVIA Centaur (n = 9)]. The target value for each component was calculated based on the mean of method means or measured by a reference measurement procedure (free T4). Quality specifications were based on biological variation. Local reference intervals were reported from all laboratories. Method differences that exceeded acceptable bias were found for all components except folate. Free T4 differences from the uncommonly used reference measurement procedure were large. Reference intervals differed between measurement procedures but also within 1 measurement procedure. The serum X material was commutable for all components and measurement procedures, whereas the EQA materials were noncommutable in 13 of 50 occasions (5 components, 5 methods, 2 EQA materials). The bias between the measurement procedures was unacceptably large in 4/5 tested components. Traceability to reference materials as claimed by the manufacturers did not lead to acceptable harmonization. Adjustment of reference intervals in accordance with method differences and use of commutable EQA samples are not implemented commonly. © 2016 American Association for Clinical Chemistry.

  7. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

    Directory of Open Access Journals (Sweden)

    Sayaka Akieda-Asai

    Full Text Available BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5Kgamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268 in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5P(2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

  8. Regulation of Thyroid Hormone Bioactivity in Health and Disease

    NARCIS (Netherlands)

    R.P. Peeters (Robin)

    2005-01-01

    textabstractTThyroid hormone plays an essential role in a variety of metabolic processes in the human body. Examples are the effects of thyroid hormone on metabolism and on the heart. The production of thyroid hormone by the thyroid is regulated by thyroid stimulating hormone (TSH) via the TSH

  9. 促甲状腺激素受体在甲状腺癌中的表达及其临床作用探讨%Discussion of the Expression of Thyroid Stimulating Hormone Receptor in Thyroid Cancer and Its Clinical Effect

    Institute of Scientific and Technical Information of China (English)

    郭红丽; 雷川云

    2015-01-01

    Objective To analyze and investigate the expression of thyroid stimulating hormone receptor in thyroid cancer patients. Methods A retrospective analysis was conducted on the clinical data of thyroid cancer patients admitted in the Oncology Depart-ment of our hospital from April 2011 to March 2015. And other 30 healthy people with normal thyroid function were selected as the control group. The thyroid tissues of the thyroid cancer patients and control group were stained by HE staining and measured by immunohistochemistry for detecting the expression of thyroid stimulating hormone receptor. Results The results showed that thy-roid stimulating hormone receptor in normal thyroid tissue and the thyroid tissue of thyroid cancer patients expressed, but the latter coloring was shallow, the expression site was located in the base side of the cell membrane. The positive expression rate of thyroid stimulating hormone receptor in the normal thyroid tissues was 100% (30/30), significantly higher than 84.84% (28/33) in thyroid tumor patients and 68.75%(22/32) in thyroid cancer patients. And the positive rate of thyroid stimulating hormone receptor in thy-roid tumor patients was significantly higher than that in thyroid cancer patients with statistically significant difference ( P<0.05). Conclusion The results suggested that the expression of thyroid stimulating hormone receptor in the normal thyroid tissue is high-er, but with the degree of differentiation of the thyroid tissue decreases, the expression decreases significantly, which provides an important reference for the TSH suppression therapy in differentiated thyroid cancer patients.%目的 分析和探讨甲状腺癌患者体内促甲状腺激素受体表达情况. 方法 对整群选取的2011年4月-2015年3月该院肿瘤科收治的65例甲状腺癌患者临床资料进行回顾性分析,选取30例甲状腺功能正常的健康人作为对照组,对采集的甲状腺组织进行HE染色观

  10. TSH (Thyroid-Stimulating Hormone) Test

    Science.gov (United States)

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  11. 山羊促甲状腺素β亚基基因(TSHB)cDNA克隆与组织表达研究%cDNA cloning and tissue expression of thyroid stimulating hormone beta chain gene (TSHB) in goats

    Institute of Scientific and Technical Information of China (English)

    黄冬维; 曹贵玲; 储明星; 唐倩倩; 狄冉; 方丽

    2012-01-01

    促甲状腺素β亚基基因(TSHB)主要表达于动物垂体腺,其表达受到光照周期调控并且与动物季节性繁殖活动密切相关.本实验以济宁青山羊和辽宁绒山羊为研究对象,运用RT-PCR方法克隆获得山羊TSHB基因部分cDNA序列(GenBank No.:JQ937288),并使用RT-PCR与荧光定量PCR技术检测TSHB基因在济宁青山羊与辽宁绒山羊下丘脑-垂体-卵巢繁殖轴及其他组织的表达分布情况.结果表明,山羊TSHB基因编码区417bp,编码含有138个氨基酸的蛋白质;各哺乳动物间TSHB基因高度保守,山羊与绵羊、牛TSHB基因同源性最高,达99%;另外,两品种山羊TSHB基因均在垂体中高表达,在济宁青山羊下丘脑、卵巢及海马等组织低度表达,而在辽宁绒山羊下丘脑低度表达,两品种其他组织均没有表达.非繁殖季节济宁青山羊垂体TSHB基因表达水平是辽宁绒山羊的1.6倍(P=0.061),其对季节性繁殖的调控功能值得进一步研究.本研究首次对山羊TSHB基因cDNA序列进行了克隆和表达分析,研究结果对山羊繁殖调控具有重要意义.%Thyroid stimulating hormone beta chain (TSHB) is mainly expressed in pituitary, which is regulated intensely by photoperiod and closely related to seasonal reproduction in animals. To study the expression profile and function of goat TSHB gene, a cDNA fragment was cloned and its expression was detected in 22 tissues of goat by using RT-PCR method. TSHB gene expression in hypothalamus-pituitary-ovary axis and other four tissues was analyzed by qPCR. The results showed that whole coding region of goat TSHB gene was 417 bp in length, encoding a protein of 138 amino acid residues, which has high homology (99%) with both sheep and cattle. Moreover, TSHB gene is highly conservative in mammals. The results also indicated that goat TSHB gene was expressed abundantly in pituitaries of both Jining Grey goats and Liaoning Cashmere goats. Compared with Liaoning Cashmere goat

  12. Significance evaluation of thyroid stimulating hormone in prenatal screening%早孕期孕妇促甲状腺激素检测临床意义研究

    Institute of Scientific and Technical Information of China (English)

    黄之虎; 黄翠波; 黄小明; 贾绍府

    2014-01-01

    目的:探讨孕21-三体综合征胎儿、孕18-三体综合征胎儿和孕健康胎儿孕妇早孕期血清促甲状腺激素(TSH)水平和游离β-人绒毛膜促性腺激素(β-hCG)之间的关系,评价TSH用于早孕期产前筛查的临床价值。方法分别比较26例孕21-三体综合征胎儿、19例孕18-三体综合征胎儿和6782例孕健康胎儿孕妇孕11~13周时的血清TSH和游离β-hCG水平。结果孕21-三体综合征胎儿孕妇血清 TSH 水平较低(0.72±0.31MoM),而孕18-三体综合征胎儿孕妇血清TSH水平较高(1.48±0.57 MoM)。孕健康胎儿孕妇血清TSH和游离β-hCG水平具有负相关性(r=-0.214,P<0.05),但在孕染色体非整倍体胎儿孕妇体内,二者无相关性(孕21-三体综合征胎儿孕妇:r=-0.157,P>0.05;孕18-三体综合征胎儿孕妇:r=-0.176,P>0.05)。结论早孕期筛查 TSH 并不能有效提高21-三体综合征胎儿和18-三体综合征胎儿的检出率。%Objective To explore the relationship between thyroid stimulating hormone (TSH)and freeβ-hu-man chorionic gonadotropin (β-hCG)in maternal serum of trisomy 2 1 ,trisomy 1 8 and euploid pregnancies at 1 1-1 3 weeks and evaluate the potential value of TSH in first-trimester prenatal screening.Methods Maternal serum levels of TSH and freeβ-hCG at 11-13 weeks in 26 cases of trisomy 21 and 19 cases of trisomy 18 pregnancies were com-pared with levels in 6 782 cases of unaffected pregnancies.Results The trisomy 21 pregnancies were with lower ma-ternal serum levels of TSH (0.72±0.31 MoM)and the trisomy 18 pregnancies were with higher maternal serum levels of TSH (1.48 ±0.57 MoM).There were significant associations between TSH and freeβ-hCG in the unaf-fected pregnancies (r=-0.214,P0.05)or trisomy 18 (r=-0.176,P>0.05).Conclusion Measurement of TSH could not improve the performance of screening for tri-somy 21 and trisomy 18.

  13. Thyroid stimulating antibody: an index of thyroid stimulation in Graves' disease?

    Science.gov (United States)

    Baldet, L; Madec, A M; Papachristou, C; Stefanutti, A; Orgiazzi, J; Jaffiol, C

    1987-09-01

    Early (20 min) thyroid radio-iodine uptake (ERU) and thyroid-stimulating antibodies (TSab) were determined in 27 untreated unselected patients with Graves' disease at the time of diagnosis. In 21 subjects the same tests were further performed in parallel during combined carbimazole-L-T3 therapy (mean duration of follow-up: 10.8 +/- 5.8 months; mean +/- SD). TSab was determined by a cAMP-human thyrocyte culture stimulation assay and expressed in microliter-equivalent of a TSab standard/ml (microliter-eq/ml). Before treatment, ERU, ranging from 15 to 54% of the injected dose (normal less than or equal to 8% dose) correlated with serum T3 (r: 0.54; P less than 0.01); TSab, ranging from 6 to 85 microliter-eq/ml was detected in 21/27 patients. There was a significant correlation between ERU and TSab (Spearman rank test: r: 0.57; P less than 0.01). During the first months of treatment, 5 of the 21 patients sequentially studied had undetectable TSab levels throughout the study and in these patients ERU decreased by 57% of its initial value; the remaining 16 subjects were divided into two groups according to ERU changes: in group A (9 patients), initial ERU decreased by 50% or more or the absolute value became less than 20% of the dose and TSab decreased from 10.9 +/- 4.8 microliter-eq/ml to 5.3 +/- 1.6 microliter-eq/ml (P less than 0.01); in group B (7 patients), the fall of ERU was less than 50% or the absolute value remained greater than 20% of the dose and TSab values remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The relationship between thyroid papillary carcinoma and serum thyroid stimulating hormone%甲状腺乳头状癌颈侧区淋巴结转移与血清促甲状腺激素的相关关系研究

    Institute of Scientific and Technical Information of China (English)

    马飞国; 王红军

    2015-01-01

    Objective To investigate the relationship between serum thyroid stimulating hormone level and lymph node metastasis in papillary thyroid carcinoma. Methods The clinical data of 127 patients with thyroid papillary carcinoma and 50 patients with benign thyroid nodules were retrospectively analyzed.We also analyzed the serum level of thyroid stimulating hormone and thyroid papillary carcinoma metastasized to cervical lymph nodes and other pathological data.SPSS 20.0 software package was used for data analysis.The pathological data, TSH level and other measurement data of the patients were expressed as mean ± SD and examined by Student’s t test.P<0.05 was statistically significant. Results The TSH level in thyroid cancer patients was (2.4 ±0.7) μIU /mL and (1.2 ±0.5) μIU /mL in patients with thyroid nodules.The TSH level of patients with thyroid carcinoma was significantly higher than that of patients with thyroid nodules(t =12.750, P<0.01). There was a significant increase in TSH levels in patients with metastasis to cervical lateral lymph nodes, TNM staging, calcification, and tumor diameter ≥1 cm ( t =12.676, 4.940, 11.149, 6.803, P <0.01 ). Conclusion Serum thyroid stimulating hormone levels are closely related to the occurrence and development of papillary thyroid carcinoma, which is an important indicator for predicting lymph node metastasis and staging.%目的:探讨血清促甲状腺激素(TSH)水平与甲状腺乳头状癌颈侧区淋巴结转移的关系。方法回顾性分析2010年1月至2014年12月收治的127例甲状腺乳头状癌患者和50例甲状腺良性结节患者临床资料。应用SPSS 20.0软件包进行数据处理,患者的病理资料、TSH水平等以(x珋±s)表示,采用t检验。P<0.05为差异具有统计学意义。结果甲状腺癌患者的TSH为(2.4±0.7)μIU/ml显著高于甲状腺结节患者(1.2±0.5)μIU/ml(t =12.750, P<0.01)。存在颈侧区淋巴结转移、

  15. 左甲状腺素钠治疗妊娠亚临床甲减与促甲状腺激素水平的关系研究%Relationship between levothyroxine sodium and the level of thyroid stimulating hormone in the treatment of pregnancy subclinical low thyroid function

    Institute of Scientific and Technical Information of China (English)

    张春明; 王东

    2014-01-01

    Objective To study the effect of levothyroxine sodium (L-T4) for thyroid peroxidase antibody positive patients with subclinical low thyroid function during the early pregnancy ,to explore the correlation between the dosage of L-T4 when the level of thyroid-stimulating hormone (TSH) controlled to the target durning the middle pregnancy and the level of TSH before intervention .Methods According to the level of TSH ,one hundred and twen-ty four early pregnancy patients with subclinical low thyroid function and TPOAb positive were divided into three groups .All the patients were treated with L-T4 ,compared the differences of the body weight ,the dosage of L-T4 be-tween before intervention and after the level of thyroid-stimulating hormone (TSH) controlled to the target durning the middle pregnancy .Results There was no significant difference in the body weight among the three groups before intervention and after the level of thyroid-stimulating hormone (TSH ) controlled to the target durning the middle pregnancy(P> 0 .05) ,while there was significant difference in the dosage of L-T4 between the two periods (P<0 .05) .Conclusion While there was no significant difference in the pregnancy early subclinical low thyroid function patients with TPOAb positive ,and the level of TSH controlled to the target in the middle of pregnancy ,the dosage of L-T4 was associated with the level of TSH in early pregnancy .%目的:探讨左甲状腺素钠(L-T 4)治疗妊娠早期亚临床甲状腺功能减退症(亚临床甲减)抗甲状腺过氧化物酶自身抗体(TPOAb)阳性患者的疗效,并探讨在妊娠中期促甲状腺激素(TSH)水平控制至目标值时的 L-T 4用量与干预前T S H水平的关系。方法选择2012年3~11月辽宁中医药大学附属医院124例妊娠早期亚临床甲减伴TPOAb阳性患者为研究对象,根据首次TSH水平划分为A、B、C 3组,每组均给予L-T4治疗,检测干预前及妊娠中期TSH控制至目

  16. 超声弹性成像应变率评价桥本甲状腺炎进程的可行性%Correlational study between ultrasonic elastography strain ratio and serum thyroid stimulating hormone on patients with Hashimoto's thyroiditis

    Institute of Scientific and Technical Information of China (English)

    闫玉玺; 原韶玲; 杨立; 翟建敏; 王慧芳

    2012-01-01

    目的探讨超声弹性成像应变率值(strain ratio,SR)对桥本甲状腺炎(Hashimoto's thyroiditis,HT)的诊断价值.方法 收集116例经临床确诊的HT患者,根据甲状腺功能分为甲状腺功能亢进组、甲状腺功能正常组、亚临床甲状腺功能减低组、临床甲状腺功能减低组,并以50例甲状腺功能正常者作为对照组,测量甲状腺与同侧颈部胸锁乳突肌的SR,分别统计各组间SR的差异,并分析其与血清促甲状腺激素(thyroid stimulating hormone,TSH)的相关性.结果 SR甲状腺功能亢进组<对照组<甲状腺功能正常组<亚临床甲状腺功能减低组<临床甲状腺功能减低组,HT的SR与血清TSH呈显著正相关(r =0.605,P=0.000).结论 超声弹性成像SR法有助于评价HT的病程进展情况.%Objective To investigate the value of strain ratio (SR) in the diagnosis of Hashimoto's thyroiditis.Methods 116 patients who had been diagnosed clinically as Hashimoto' s thyroiditis were enrolled in the study.Those patients were classified into four groups:the hyperthyroidism group,the euthyroidism group,the subclinical hypothyroidism group,and the clinical hypothyroidism group.50volunteers with normal thyroid functions were enrolled as a control group.SR of the thyroid and sternocleidomastoid muscle of same side was calculated.The correlation coefficient between the elasiticity SR and the serum thyroid stimulating hormone (TSH) was evaluated and their differences in the diagnosis of Hashimoto's thyroiditis were compared.Results The Spearman's correlation coefficient between the SR and the serum TSH was 0.605,which was significant (P =0.000).The SR increased in an ascending order among the group with hyperthyroidism,the control group,the group with euthyroidism,the group with subclinical hypothyroidism,and the group with clinical hypothyroidism.Conclusions Elastography SR is valuable way for evaluating the progression of Hashimoto's thyroiditis.

  17. Study and Analysis of 1350 Women with Early Pregnancy Thyroid Stimulating Hormone Levels%1350例育龄女性孕期促甲状腺激素水平筛查研究与分析

    Institute of Scientific and Technical Information of China (English)

    赵世荣

    2014-01-01

    目的通过对妊娠甲状腺功能筛查,了解女性不同孕期体内促甲状腺激素水平,探讨异常结果的产生因素与预防控制。方法选取2014年1月~4月在我院进行甲状腺功能筛查的1350例孕妇作为本组研究的观察对象,按照孕期分为孕早期组(416例)孕中期组(837例)孕晚期组(97例),同时选取此期间内在我院进行健康体检的50例健康妇女作为对照组,归纳并总结育龄妇女的甲状腺相关激素水平特点。结果妊娠期女性的血清甲状腺激素水平均与对照组有明显差异,具有统计学意义(P<0.05),其中孕早期孕妇的FT4水平明显高于孕晚期孕妇,差异明显,具有统计学意义(P<0.05)。结论妇女妊娠期内的甲状腺激素水平与孕期及孕妇年龄有直接关系,而且相互之间存在明显差异,因此强调孕产前甲状腺激素水平的检测与筛查,以提高妊娠结局,保证优生优育工作的落实。%Objective To investigate the women of childbearing age in the thyroid hormone level in dif erent periods, dif erent ages. Methods 1358 cases were divided into early pregnancy group, the second trimester pregnant women group, late pregnancy group and 20~29 group, the 30-35 years old group, above 36 years old group, the thyroid hormone levels each group of the period of 50 healthy women health examination in our hospital (control group) were compared, the level of thyroid hormone and summarizes the related characteristics of women of childbearing age. Results Pregnant women serum thyroid hormones were significantly dif erence with the control group, the FT4 level was significantly higher than that in early pregnancy.Conclusion The pregnant period of thyroid hormone levels have a direct relationship with the pregnancy and maternal age, ensure the implementation of the work of the eugenics in order to improve the outcome of pregnancy.

  18. Asseciation of TNF-α gene polymorphisms with Graves disease susceptibility and early course thyroid stimulating hormone receptor antibody level in Chinese Han population in Anhui region%肿瘤坏死因子-α基因多态性与安徽地区汉族人群Graves病易感性及患病早期TRAb水平的关联

    Institute of Scientific and Technical Information of China (English)

    潘天荣; 邢时妹

    2012-01-01

    目的 检测肿瘤坏死因子-a(tumour necrosis factor-α,TNF-α)基因启动子区的—863C/A、—857C/T、—238G/A等3个位点的单核苷酸多态性与格雷夫斯氏病(Graves disease,GD)与安徽地区汉族人群中发病的相关性,以探讨与GD有关的遗传背景.方法 应用聚合酶链式反应-序列特异性引物法(polymerase chain reaction and sequence specific primers,PCR-SSP)检测254例Graves病患者和212名正常对照TNF-α基因启动子区—863C/A、—857C/T、—238G/A三个位点的单核苷酸多态性,比较GD患者组与正常对照组、不同性别的GD患者之间的等位基因和基因型频率的分布情况.同时采用放射性免疫法测定早期GD患者的促甲状腺激素受体抗体(thyroid stimulating hormone receptor antibody,TRAb)水平,比较不同TRAb水平患者TNF-α基因这3个多态位点等位基因及基因型的频率分布情况.结果 (1)GD组—863 C/A位点A等位基因频率(16.73%)高于正常对照组(11.79%)(P<0.05,OR=1.503);GD组AA+CA基因型频率(32.68%)明显高于正常对照组(23.58%) (P<0.05,OR=1.573).—857 C/T、—238G/A位点等位基因及基因型频率在GD组与正常对照组间的差异均无统计学意义(P>0.05).(2)将GD组按性别分组比较,结果显示3个位点的基因型及等位基因频率在男、女性间差异均无统计学意义(P>0.05).(3)将早期GD患者按TRAb水平分组比较,结果显示3个位点的等位基因和基因型频率差异均无统计学意义(P>0.05).结论 TNF-α基因—863C/A单核苷酸多态性可能与安徽地区汉族人群GD的发病具有相关性,而—857C/T、—238G/A位点的单核苷酸多态性与之无相关性;患者早期TRAb水平和GD患者的性别与TNF-α基因—863C/A、—857C/T、—238G/A三个位点的单核苷酸多态性无关联.%[Objective]To assess the association of tumour necrosis factor-α (TNF-α) gene polymorphisms at positions—863C/A,—857C/T,—238G/A and Graves

  19. Validation of cytochemical section bioassay for thyroid-stimulating immunoglobulins in treated and untreated Graves' disease.

    Science.gov (United States)

    Prentice, M G; Alaghband-Zadeh, J; Wise, P H

    1984-01-01

    The cytochemical section-bioassay of thyroid stimulating activity is described. Plasma of thyrotoxic patients as well as those on block-replace treatment with carbimazole and thyroid hormones was used. Linear parallel responses were obtained over the range 1.5 X 10(-7) to 1.5 X 10(-5) mU/1 MRC LATS-B standard. The index of precision was 0.19 +/- 0.028. The fiducial limits (p=0.95) of a sample tested on ten separate occasions were 52-192%. Specificity was investigated using time course studies, and the effect of anti-TSH or anti-IgG antisera. No effect of methimazole or a variety of other drugs was detected. The assay is accordingly validated for measurement of TSI in patients both untreated and on block-replace therapy.

  20. Levels of serum bone gla protein and thyroid-stimulating hormone in patients with subclinical hyperthyroidism after 131iodine therapy%131碘治疗后亚临床甲状腺功能亢进患者血清骨钙蛋白与促甲状腺素水平变化

    Institute of Scientific and Technical Information of China (English)

    张海三; 张红星; 刘保平

    2012-01-01

    了解131碘治疗后亚临床甲状腺功能亢进患者血清骨钙蛋白(BGP)水平变化及其与血清促甲状腺激素(TSH)的关联.方法:279例患者131碘治疗后随访1年,应用放射免疫分析法于随访6个月(6m)、12个月(12m)时测定血清甲状腺相关激素水平(FT3、FT4、TSH)和血清BGP,根据血清甲状腺相关激素水平分为亚临床甲状腺功能亢进组(亚甲组,73例)、康复组(206例),另选择132例相匹配的志愿者为健康对照组(对照组),SPSS 13.0软件分析不同时间3组间血清BGP、TSH水平差异及二者相关性.结果:3组间6个月与12个月时血清BGP水平均有统计学差异(Fσm=852.71,Pσm=0.000;F12m=1 053.56,P12m=0.000);两两比较,差异均有显著性(P< 0.001),亚甲组血清BGP高于其他两组;病例组血清BGP与血清TSH相关系数r=-0.568,P=0.000.结论:131碘治疗后亚临床甲亢患者血清BGP水平异常增高,其升高可能与低TSH相关.%Objective To analyze the levels of serum bone gla protein (BGP) and thyroid-stimulating hormone (TSH) and observe the relationship of them from the patients with subclinical hyperthyroidism after 131iodine therapy. Methods BGP and TSH were detected by using radio immunoassay in 73 patients with subclinical hyperthyroidism, 206 cases recovered hyperthyreosis patients after 131iodine therapy and 132 cases as health controls. SPSS soft was used to analyze the difference of the levels of BGP among the three groups and the correlation between serum BGP and TSH. Results There were significant differences of serum BGP among the three groups at the end of 6 moths and 12 moths (F6m = 852.71 ,P^ = 0.000;F12m = 1 053.56,P12m = 0.000). And there was significant difference between any two groups, and it was the highest in subclinical hyperthyroidism group. In two patients groups, there was positive correlation between BGP and TSH (r = -0.568,P = 0.000). Conclusion BGP increased in patients with subclinical hyperthyroidism after 131iodine

  1. Different short-term effect of protein and carbohydrate intake on TSH, growth hormone (GH), insulin, C-peptide, and glucagon in humans

    DEFF Research Database (Denmark)

    Matzen, L E; Andersen, B B; Jensen, B G

    1990-01-01

    hormone (GH) and thyroid stimulating hormone (TSH) to protein and carbohydrate was identical, with a reduction in both GH and TSH, and nadir occurring after 45-60 min and 120 min, respectively. During the next 120 min TSH returned to starting level after carbohydrate intake but was still reduced after...... protein intake (p less than 0.04). After both diets GH increased after the initial decline, the increase was greatest after protein intake and maximum was reached at 180 min (p less than 0.02). It has been reported that the 5'-deiodination of T4 is stimulated by insulin and inhibited by glucagon......The effect of isocaloric (500 kcal) protein and carbohydrate ingestion was studied in a crossover study in nine healthy humans. Subjects were studied twice after overnight fasting, with an interval of 3 to 7 days. Blood was collected for 240 min after food ingestion. The initial reaction of growth...

  2. 猪促甲状腺激素β基因(TSH-β)多态分布及与经济性状的关联分析%Genetic Variation of Porcine Thyroid-stimulating Hormone β Subunit Gene(TSH-β) and Its Association with the Economic Important Traits

    Institute of Scientific and Technical Information of China (English)

    蒋晓玲; 蔡兆伟; 张立凡; 华绪川; 周红梅; 陈哲; 王颖; 徐宁迎

    2011-01-01

    为研究猪促甲状腺激素口基因(TSH-β)的多态分布情况及与生长肉质性状的关联性,本研究对TSH-β基因全序列进行再测序,发现3个单核苷酸突变座位:位于5'非转录区多态座位A-175G、位于编码区非同义突变座位G+52A,以及位于内含子的突变座位G+570A.采用PCR-RFLP和四引物ARMS-PCR方法对皮特兰、长白、杜洛克、约克夏、金华猪、岔路黑猪和嘉兴黑猪七个纯种猪群以及金皮资源家系F2代群体共计548头个体进行多态分型,并在F2代群体中分析了TSH-β多态座位与生长和肉质性状的关联性.结果表明,猪TSH-β基因具有较高的遗传多样性(Shannon多样性指数总体均值为0.48),且存在相当程度的品种间遗传分化(Fst=0.5389).其中,座位A-175G在4个国外品种和岔路黑猪中的优势等位基因为A,而在金华猪和嘉兴黑猪中的优势等位基因为G,关联分析显示AA型个体在胴体长、日增重、后腿重和后腿肌肉重方面显著高于GG型个体(P<0.05):座位G+52A的多态性主要存在于金华猪中,而在其他猪种中表现为低杂合度或完全纯合于等位基因G,且与肌内脂肪含量有显著关联;座位G+570A的多态性仅存在于我国的嘉兴黑猪和金华猪中,其他猪种表现为完全纯合于等位基因G,关联分析结果表明GG型个体在胴体长和后腿肌肉重方面显著高于AA型个体.研究结果提示,TSH-β基因可考虑为猪4号染色体相关QTL的功能候选基因.%The objective of this study was to identify polymorphisms of porcine thyroid-stimulating hormone β subunit gene (TSH-β) and investigate its associations with porcine carcass and meat quality traits.Three SNP were identified by resequencing the entire genomic sequence of porcine TSH-β gene: A-175G located in the 5'untranscribed region, non-synonymous mutation G+52A located in the coding region and G+570A located in the intron.These three loci were genotyped in total of 548 pigs

  3. Influence of basic thyroid-stimulating hormone levels on outcomes of IVF/ICSI in Qinghai%青海地区不孕症患者基础促甲状腺素水平对IVF/ICSI结局的影响

    Institute of Scientific and Technical Information of China (English)

    曾湘晖; 王莉云; 舒晓巍; 熊正芳; 党小红

    2014-01-01

    Objective To study basic thyroid stimulating hormone (bTSH) levels impact on outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in Qinghai.Methods Totally 282 cases with IVF cycles and 93 cases with ICSI cycles were studied prospectively,according to bTSH level,patients were divided into four groups.Reproduction rate,clinical pregnancy rate,miscarriage rate and live birth rate were studied among four groups.Results (1) In 375 cases with IVF/ICSI cycles,bTSH was positively correlated with abortion rate (r=0.42,P=0.04),but live birth rate and growing rate showed negative correlations with bTSH (r=-0.42,-0.28; P=0.04,0.03).bTSH and the number of eggs,the number of fertilized eggs,the number of embryos,biochemical pregnancy rate,and clinical pregnancy rate were no significant correlation (all P>0.05).(2) Among women at group of ≤1.7,>1.7 and ≤2.5,>2.5 and ≤3.5,>3.5 mU/L,the implantation rates were 28.7%,27.3%,37.7% and 19.2%,live birth rates were 80.9%,75.0%,82.7%,and 59.8%,abortion rates were 19.0%,15.0%,16.7%,40.1%; they all showed significant difference (all P<0.05).Abortion rate in women with high bTSH level was higher than that of women with lower bTSH level,however implantation rate,live birth rate in women with high bTSH level were lower.Conclusion When bTSH level is >3.5 mU/L,the abortion rate were increased,but live birth rate,rate of implantation were decreased.%目的 探讨青海地区不孕症患者基础促甲状腺素(bTSH)水平对体外受精(IVF)或卵母细胞胞质内单精子注射法(ICSI)治疗结局的影响.方法 前瞻性分析2012年1月1日至2013年12月31日青海省人民医院生殖中心282个IVF周期和93个ICSI周期,根据患者的bTSH水平分为4个区间(≤1.7、>1.7~≤2.5、>2.5~≤3.5、>3.5 mU/L),观察不同bTSH水平不孕症患者行IVF/ICSI治疗后的种植率、生化妊娠率、临床妊娠率、流产率、活

  4. 促甲状腺激素β剪接变体在自身免疫性甲状腺炎小鼠甲状腺中的表达%Expression of thyroid stimulating hormone β splice variant in thyroid of mouse with autoimmune thyroiditis

    Institute of Scientific and Technical Information of China (English)

    袁继红; 周晓丽; 史亚男; 郑楠; 刘欣; 李兰英

    2014-01-01

    下降(nmol/L:67.75±11.91比45.50±3.85,t=3.55,P<0.05);TG+ HI组FT4和TSHβ剪接变体表达升高(pmol/L:54.07±3.67比139.46±30.00;×10-3:4.11±0.32比5.33±1.47;t值分别为-5.65、-5.95,P均<0.05).结论 Tg诱发了BALB/c小鼠自身免疫性甲状腺炎症反应,小鼠甲状腺中TSHβ剪接变体的表达明显升高,高碘可以加重Tg的这种反应,TSHβ剪接变体参与了自身免疫性甲状腺炎的病理过程.%Objective To investigate the expression of marrow-derived thyroid stimulating hormone β (TSHβ) splice variant in thyroid of mouse with autoimmune thyroiditis induced by thyroglobulin(Tg) immunization,and to analyze whether TSHβ splice variant participated in the pathological process of autoimmune thyroiditis.Methods Using random number table,forty-eight mice(24 females and 24 males) of 7 to 8 weeks old with body mass 20 to 25 g were randomly divided into 4 groups(12 females and 12 males in each group) based on body weight and gender.The control group:fed with deionized water; the Tg-treated group(TG):fed with deionized water,and immunized subcutaneously with 0.1 mg Tg at 8 weeks old,boost immunized twice at 11 and 15 weeks old,respectively; the high iodine-treated group (HI):fed with deionized water containing 0.05% sodium iodide (NaI); the Tg combined with HI group (TG + HI):fed with deionized water containing 0.05% NaI,and immunized the same way as the TG group did.Peripheral blood was collected after 8 weeks treatment,which was used for determination of total tetraiodothyronine (TT4),free tetraiothyronine (FT4),total triiodothyronine (TT3) and free triiodothyronine (FT3) with chemiluminescence immunoassay (CIA); thyroid glands were collected to examine the expression of TSHβ splice variant with SYBR Green fluorescent quantitative real-time PCR,and frozen sections were HE stained for observation of histopathological changes of thyroid cells under light microscopy.Results Under naked eyes,the thyroid gland enlarged

  5. Fundamentals of Thyroid Hormone Physiology, Iodine Metabolism ...

    African Journals Online (AJOL)

    of iodine and thyroid stimulating hormone (thyrotropin, TSH). To produce T4 at ... for adequate T4 release, a number of factors can modify this ..... Lipid M etabolism. R educed appetite; impaired protein metabolism; reduced glucose deposition.

  6. Sexual hormones in human skin.

    Science.gov (United States)

    Zouboulis, C C; Chen, W-C; Thornton, M J; Qin, K; Rosenfield, R

    2007-02-01

    The skin locally synthesizes significant amounts of sexual hormones with intracrine or paracrine actions. The local level of each sexual steroid depends upon the expression of each of the androgen- and estrogen-synthesizing enzymes in each cell type, with sebaceous glands and sweat glands being the major contributors. Sebocytes express very little of the key enzyme, cytochrome P450c17, necessary for synthesis of the androgenic prohormones dehydroepiandrosterone and androstenedione, however, these prohormones can be converted by sebocytes and sweat glands, and probably also by dermal papilla cells, into more potent androgens like testosterone and dihydrotestosterone. Five major enzymes are involved in the activation and deactivation of androgens in skin. Androgens affect several functions of human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing. Their effects are mediated by binding to the nuclear androgen receptor. Changes of isoenzyme and/or androgen receptor levels may have important implications in the development of hyperandrogenism and the associated skin diseases such as acne, seborrhoea, hirsutism and androgenetic alopecia. On the other hand, estrogens have been implicated in skin aging, pigmentation, hair growth, sebum production and skin cancer. Estrogens exert their actions through intracellular receptors or via cell surface receptors, which activate specific second messenger signaling pathways. Recent studies suggest specific site-related distribution of ERalpha and ERbeta in human skin. In contrast, progestins play no role in the pathogenesis of skin disorders. However, they play a major role in the treatment of hirsutism and acne vulgaris, where they are prescribed as components of estrogen-progestin combination pills and as anti-androgens. These combinations enhance gonadotropin suppression of ovarian androgen production. Estrogen-progestin treatment can reduce the need for shaving

  7. Information for People Treated with Human Growth Hormone (Summary)

    Science.gov (United States)

    ... NHPP): Information for People Treated with Pituitary Human Growth Hormone (Summary) How did Creutzfeldt-Jakob disease (CJD) occur in people treated with pituitary human growth hormone (hGH)? From 1963 to 1985, the National Hormone ...

  8. The effects of TSH on human vascular endothelial cells and smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    田利民

    2014-01-01

    Objective To study the effect of thyroid-stimulating hormone(TSH)on human vascular endothelial cells and smooth muscle cells and to explore the roles of TSH in the development of atherosclerosis.Methods Human vascular endothelial cells and smooth muscle cells were cultured in vitro.MTT method was used to assay the effect of TSH on cell viability.Real-time PCR was used

  9. Hormones and Human and Nonhuman Primate Growth.

    Science.gov (United States)

    Bernstein, Robin Miriam

    2017-01-01

    The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

  10. Human Growth Hormone: The Latest Ergogenic Aid?

    Science.gov (United States)

    Cowart, Virginia S.

    1988-01-01

    Believing that synthetic human growth hormone (hGH) will lead to athletic prowess and fortune, some parents and young athletes wish to use the drug to enhance sports performance. Should hGH become widely available, its abuse could present many problems, from potential health risks to the ethics of drug-enhanced athletic performance. (JL)

  11. Dimerization of Human Growth Hormone by Zinc

    Science.gov (United States)

    Cunningham, Brian C.; Mulkerrin, Michael G.; Wells, James A.

    1991-08-01

    Size-exclusion chromatography and sedimentation equilibrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn2+-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn2+-hGH dimeric complex may be important for storage of hGH in secretory granules.

  12. Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation

    NARCIS (Netherlands)

    M.W.P. Bruysters (Martijn); M. Verhoef-Post (Miriam); A.P.N. Themmen (Axel)

    2008-01-01

    textabstractThe luteinizing hormone (LH) receptor plays an essential role in male and female gonadal function. Together with the follicle-stimulating hormone (FSH) and thyroid stimulating hormone (TSH) receptors, the LH receptor forms the family of glycoprotein hormone receptors. All glycoprotein ho

  13. Random Secretion of Growth Hormone in Humans

    Science.gov (United States)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  14. Illness-induced changes in thyroid hormone metabolism: focus on the tissue level

    NARCIS (Netherlands)

    J. Kwakkel; E. Fliers; A. Boelen

    2011-01-01

    During illness changes in thyroid hormone metabolism occur, collectively known as the non-thyroidal illness syndrome (NTIS). NTIS is characterised by low serum thyroid hormone levels without the expected rise in serum thyroid-stimulating hormone, indicating a major change in thyroid hormone feedback

  15. Thyroid Stimulating Hormone Is Increased in Hypertensive Patients with Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Nanfang Li

    2016-01-01

    Full Text Available Purpose. To evaluate alteration in serum TSH in hypertensives with OSA and its relation with cardiometabolic risk factors. Methods. 517 hypertensives were cross-sectionally studied. OSA was determined by polysomnography and thyroid function by standard methods. Results. OSA was diagnosed in 373 hypertensives (72.15%. Prevalence of subclinical hypothyroidism was significantly higher in OSA hypertensives than in non-OSA ones (15.0% versus 6.9%, P=0.014. Serum LnTSH in hypertensives with severe OSA was significantly higher (0.99±0.81 versus 0.74±0.77 μIU/mL, P<0.05 than in those without OSA. AHI, LSaO2, ODI3, and ODI4 were independently associated with serum TSH for those aged 30–65 years. Dividing subjects into four groups as TSH < 1.0 μIU/mL, 1.0 ≤ THS ≤ 1.9 μIU/mL, 1.91 ≤ TSH < 4.5 μIU/mL, and TSH ≥ 4.5 μIU/mL, only 26.3% of OSA subjects exhibited TSH between 1.0 and 1.9 μIU/mL, significantly less than non-OSA subjects (26.3% versus 38.2%, P=0.01. DBP and serum LDL-c elevated with TSH increasing and were only significantly higher in TSH ≥ 4.5 μIU/mL group than in 1.0 ≤ TSH ≤ 1.9 μIU/mL group (96.32±14.19 versus 92.31±12.86 mmHg; P=0.040; 0.99±0.60 versus 0.87±0.34 mmol/L, P=0.023. Conclusion. OSA might be a risk factor for increased TSH even within reference range in hypertensive population.

  16. Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease

    Directory of Open Access Journals (Sweden)

    Hyemi Kwon

    2016-06-01

    Full Text Available BackgroundHyperthyroidism relapse in Graves disease after antithyroid drug (ATD withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb and thyrotropin-binding inhibitory immunoglobulin (TBII at ATD withdrawal to predict relapse.MethodsThis retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35 or TBII (TBII group; n=39 every 3 to 6 months for 2 years after ATD withdrawal.ResultsTwenty-eight patients (38% relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67% than patients with negative TSAb (17%; P=0.007. Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%.ConclusionTSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

  17. Autodecomposition of radiolabeled human growth hormone

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, G.; Amburn, K.

    1986-01-01

    Human growth hormone (hGH) was radiolabeled with /sup 125/I, using a gentle lactoperoxidase technique. The stability and decomposition products of this tracer were studied by frequent periodic analysis by Sephadex G-100 chromatography on a long column. Monomeric /sup 125/I-hGH showed an exponential decline, with a half-life of 61 days. The main radioactive degradation product was iodide, which appeared with a fractional appearance rate of 0.01136 per day. Secondary degradation products were a series of radioactive oligomers of hGH, which appeared with an overall fractional rate of 0.00525 per day. The kinetic data obtained should provide guidelines for the shelf-life and repurification schedule of radioiodinated polypeptides.

  18. Different short-term effect of protein and carbohydrate intake on TSH, growth hormone (GH), insulin, C-peptide, and glucagon in humans

    DEFF Research Database (Denmark)

    Matzen, L E; Andersen, B B; Jensen, B G

    1990-01-01

    hormone (GH) and thyroid stimulating hormone (TSH) to protein and carbohydrate was identical, with a reduction in both GH and TSH, and nadir occurring after 45-60 min and 120 min, respectively. During the next 120 min TSH returned to starting level after carbohydrate intake but was still reduced after...... protein intake (p less than 0.04). After both diets GH increased after the initial decline, the increase was greatest after protein intake and maximum was reached at 180 min (p less than 0.02). It has been reported that the 5'-deiodination of T4 is stimulated by insulin and inhibited by glucagon...

  19. Minireview: Hormones and human sexual orientation.

    Science.gov (United States)

    Balthazart, Jacques

    2011-08-01

    Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa). In animals and men, many sexually differentiated characteristics are organized during early life by sex steroids, and one can wonder whether the same mechanism also affects human sexual orientation. Two types of evidence support this notion. First, multiple sexually differentiated behavioral, physiological, or even morphological traits are significantly different in homosexual and heterosexual populations. Because some of these traits are known to be organized by prenatal steroids, including testosterone, these differences suggest that homosexual subjects were, on average, exposed to atypical endocrine conditions during development. Second, clinical conditions associated with significant endocrine changes during embryonic life often result in an increased incidence of homosexuality. It seems therefore that the prenatal endocrine environment has a significant influence on human sexual orientation but a large fraction of the variance in this behavioral characteristic remains unexplained to date. Genetic differences affecting behavior either in a direct manner or by changing embryonic hormone secretion or action may also be involved. How these biological prenatal factors interact with postnatal social factors to determine life-long sexual orientation remains to be determined.

  20. Single dose and pulsatile treatment with human growth hormone in growth hormone deficiency.

    OpenAIRE

    P. J. Smith; Pringle, P J; Brook, C. G.

    1987-01-01

    The growth and growth hormone profiles in four children receiving three different regimens of treatment with human growth hormone (hGH) were compared. There was no significant difference in the rate of growth between the regimens; the rate of growth fell dramatically after treatment. Pulsatile administration of hGH was no better than conventional treatment.

  1. Thyroid hormone resistance may course hypotonia in infancy

    DEFF Research Database (Denmark)

    Pivkovska, Julijana; Born, Alfred Peter; Nielsen, Claus Thøger

    2014-01-01

    Allan Herndon Dudley's syndrome (AHDS) is X-linked mental retardation and hypotonia caused by mutations in a thyroid hormone transporter gene - MCT8. The typical thyreoidea AHDS profile is elevated T3, low-normal T4 and normal or elevated thyroid stimulating hormone (TSH). Neonatal screening...

  2. Radioreceptor assay for TBII in the spectrum of thyroid stimulating immunoglobulins

    Energy Technology Data Exchange (ETDEWEB)

    Bliddal, H.

    1986-01-01

    Thyroid stimulating immunoglobulins have been measured by several different methods among which the radioreceptor assay for TBII has been mostly employed. This technique is review in detail and it is concluded that the present method has the advantage of a larger stability aquired by the use of a purified plasma membrane fraction produced from autopsy material. TBII has been found in 60 to 80 percent in untreated Graves' disease while the percentage of positive patients decreases after any kind of treatment. Thus, TBII descreases during long term antithyroid treatment and by the end of such treatment TBII has a certain prognostic value. In the present study TBII was correlated to several other methods of measurement, primarily with the thyroid adenylate cyclase stimulating antibodies. In Graves's disease a general correlation was found with significant differences in TBII and TSAb activity in some cases. In contrast, a dissociation between two tests was often found in Hashimoto's thyroiditis and several other diseases with a low occurence of these antibodies, e.g. IDDM. Based on the present results it is concluded that thyroid stimulating immunoglobulins are heterogenous and probably polyclonal antibodies directed against several different epitopes on the TSH receptor with different affinity for the binding side of TSH. An activation in vitro by adenylate cyclase is apparently possible by-passing this binding side, and in some sera antibodies have been described which block the adenylate cyclase in vitro without affecting the binding of TSH. It is concluded that these antibodies are a major factor in the pathogenesis of thyrotoxicosis in Graves' disease, while differences in expression and affinity of antibodies against the TSH receptor may explain the lack of clinical correlation in other diseases. 193 refs.

  3. Hormonal contraception for human males: prospects

    Institute of Scientific and Technical Information of China (English)

    P.R.K.Reddy

    2000-01-01

    Development of an ideal hormonal contraceptive for man has been the goal of several research workers during the past few decades. Suppression of pituitary gonadotropic hormones, which in turn would inhibit spermatogenesis while maintaining normal libido and potentia has been the approach for a contraceptive agent. Intramuscularly administered and orally active testosterone or testosterone in combination with progesterone have been shown to cause inhibition of spermatogenesis resulting in azoospermia in normal men. Similarly testosterone has been used in combination with gonadotropin releasing hormone antagonists and agonists to inhibit pituitary gonadotropic hormone release. Immunological approach to neutralize the circulating levels of follicle stimulating hormone has also been shown to cause inhibition of spermatogenesis. The available literature shows that testosterone causes reversible azoospermia without any significant side effects in Asian population effectively and appears to be a promising chemical for control of fertility in man.( Asian J Androl 2000 ; 2 : 46 - 50 )

  4. Extrapituitary growth hormone synthesis in humans.

    Science.gov (United States)

    Pérez-Ibave, Diana Cristina; Rodríguez-Sánchez, Iram Pablo; Garza-Rodríguez, María de Lourdes; Barrera-Saldaña, Hugo Alberto

    2014-01-01

    The gene for pituitary growth hormone (GH-N) in man belongs to a multigene locus located at chromosome 17q24.2, which also harbors four additional genes: one for a placental variant of GH-N (named GH-V) and three of chorionic somatommamotropin (CSH) type. Their tandem arrangement from 5' to 3' is: GH-N, CSH-L, CSH-1, GH-V and CSH-2. GH-N is mainly expressed in the pituitary from birth throughout life, while the remaining genes are expressed in the placenta of pregnant women. Pituitary somatotrophs secrete GH into the bloodstream to act at receptor sites in most tissues. GH participates in the regulation of several complex physiological processes, including growth and metabolism. Recently, the presence of GH has been described in several extrapituitary sites, such as neural, ocular, reproductive, immune, cardiovascular, muscular, dermal and skeletal tissues. It has been proposed that GH has an autocrine action in these tissues. While the body of evidence for its presence is constantly growing, research of its possible function and implications lag behind. In this review we highlight the evidence of extrapituitary synthesis of GH in humans.

  5. [Human growth hormone and Turner syndrome].

    Science.gov (United States)

    Sánchez Marco, Silvia Beatriz; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José Ignacio; Garagorri Otero, Jesús María

    2017-02-01

    The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82±21.23cm (1.25±0.76 SDS), with an adult height gain of 9.59±5.39cm (1.68±1.51 SDS). Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. A bioassay for thyroid stimulating immunoglobulins of patients with Graves' disease using porcine thyroid monolayer cells.

    Science.gov (United States)

    Fukue, Y; Uchimura, H; Kuzuya, N; Okano, S; Kanaji, Y; Takaku, F

    1986-06-01

    A bioassay for thyroid stimulating immunoglobulins (TSI) of patients with Graves' disease was developed by porcine thyroid monolayer cells. Thyroid cells were prepared by dispersion using collagenase and trypsin. Aliquots of the cell suspension (2 X 10(6) cells/1.5 ml/dish) in Ham's F-12 medium (pH 7.2) containing 10% calf serum and 1.5 mM Hepes were seeded and cultured in air at 36 C. On day 6 of culture, cells were incubated with test samples (IgG or bTSH) in 1 ml of serum-free, 0.5 mM IMX-included fresh medium for an additional time, and cAMP in the cells was measured by radioimmunoassay. Intracellular cAMP was increased within 5 minutes after the addition of bTSH and the maximal increase was observed after 30 min. Responses of cAMP were in a dose-related manner up to 10 mU/ml of bTSH. With the addition of IgG from untreated Graves' patients, dose-related increases in cAMP were also observed up to 10 mg/ml IgG and the maximal response was seen at 2 hours incubation. Thyroid stimulating activity in IgG's from normal subjects and patients with Graves' disease was tested with a dose of 10 mg/ml and 2 hours incubation and the activity was expressed as a percent of the control (incubated in the same experiment without IgG). One hundred forty one of 145 untreated patients showed higher activity (228 +/- 51.8%, mean +/- SD; 127-393%, range) than normal subjects (103 +/- 13.3%, mean +/- SD, n = 24; 80-129%, range). Sequential changes in TSI activity in 27 patients after initiating thionamide drugs were studied for 24 months. Initially all 27 patients showed positive TSI and 6 months later 15 remained positive. At 6 months after that, 10 of 23, 4 of 16, and 2 of 6 followed patients showed positive TSI. These results indicate that this bioassay is clinically useful for detecting TSI.

  7. Thyroid hormone metabolism and the developing human lung.

    Science.gov (United States)

    Hume, R; Richard, K; Kaptein, E; Stanley, E L; Visser, T J; Coughtrie, M W

    2001-05-01

    Thyroid hormones are involved in the regulation of fetal lung development, and maturation is accelerated in animal models by antepartum exposure to raised concentrations of the receptor-active thyroid hormone triiodothyronine and glucocorticoids. It is essential that the nature of the regulation of the spatial and temporal metabolism of iodothyronines in the human fetus and infant is known before effective therapies can be developed to modify human lung maturation. Thyroid hormone bioavailability to the human fetus is regulated in part by enzymatic deiodination and reversible sulfation of iodothyronines, with contributions from other factors such as fetomaternal and fetoamniotic hormone transfers, fetal thyroid gland production, and the activities of plasma membrane transporters mediating uptake of iodothyronines from plasma into tissues. Copyright 2001 S. Karger AG, Basel.

  8. The chicken pituitary-specific transcription factor Pit-1 is involved in the hypothalamic regulation of pituitary hormones

    NARCIS (Netherlands)

    As, van P.; Janssens, K.; Pals, K.; Groef, De B.; Onagbesan, O.M.; Bruggeman, V.; Darras, V.M.; Denef, C.; Decuypere, E.

    2006-01-01

    Pit-1 is a pituitary-specific POU-domain DNA binding factor, which binds to and trans-activates promoters of growth hormone- (GH), prolactin- (PRL) and thyroid stimulating hormone-beta- (TSHbeta) encoding genes. Thyrotropin-releasing hormone (TRH) is located in the hypothalamus and stimulates TSH, G

  9. Human growth hormone and the development of osteochondritis dissecans lesions.

    Science.gov (United States)

    Hussain, Waqas M; Hussain, Haroon M; Hussain, Mohammed S; Ho, Sherwin S W

    2011-12-01

    No single etiology regarding the cause of osteochondritis dissecans (OCD) lesions is unanimously accepted. This report documents a novel case of multiple OCD lesions affecting the left knee and a solitary defect of the right elbow in a patient with acquired human growth hormone (hGH) deficiency and supplementation. hGH deficiency and hormone replacement may be related to the development of OCD lesions.

  10. Purification and cultivation of human pituitary growth hormone secreting cells

    Science.gov (United States)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  11. Purification and cultivation of human pituitary growth hormone secreting cells

    Science.gov (United States)

    Hymer, W. C.

    1978-01-01

    The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

  12. 21 CFR 862.1370 - Human growth hormone test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  13. Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism

    DEFF Research Database (Denmark)

    Stott, David J.; Gussekloo, Jacobijn; Kearney, Patricia M.

    2017-01-01

    BACKGROUND: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large ra...

  14. Purification of human parathyroid hormone: recent studies and further observations.

    Science.gov (United States)

    Keutmann, H T; Hendy, G N; Boehnert, M; O'Riordan, J L; Potts, J T

    1978-07-01

    During the isolation of human parathyroid hormone there is an extensive loss of immuno-assayble hormone over the successive extraction steps, due in part to the presence of fragments that are soluble in 4% trichloroacetic acid. These fragments are derived from both the amino- and carboxyl-terminal regions of the hormone. The hormonal fractions precipitated with trichloroacetic acid were further purified by gel filtration and ion-exchange chromatography. At the final ion-exchange purification step, some preparations of the hormone eluted in multiple fractions. When the various components were characterized separately by immunoassay, amino acid composition, enzymic cleavage and partial sequence analysis, they were found to be closely comparable, although the most acidic fraction contained a blocked terminal amino group. Extraction of a number of batches of tissue permitted revision of the amino acid composition of human parathyroid hormone. Biosynthetic studies with labelled amino acids confirmed the absence of tyrosine and the presence of phenylalanine and threonine and localized these residues to definite regions of the molecule.

  15. Hormone Production by Epithelial Cells of Human Thymus in vitro.

    Science.gov (United States)

    Yarilin, A. A.; Sharova, N. I.; Bulanova, E. C.; Kotchergina, N. I.; Mitin, A. N.; Kharchenko, T. Yu.; Arshinov, V. Yu.

    1996-12-01

    The conditions of hormone production by human thymic stromal cell line were studied. Human thymic stromal cells did not produce any hormones in 5-day monoculture. Co-cultivation of these cells with human thymocytes induced alpha1-thymosin and thymulin production increased to 4-5 days of co-cultivation. An increase in number of human thymic stromal cells and thymocyte elimination were observed in co-culture. The maximal stimulation of proliferation and hormone secretion by human thymic stromal cell was reached in their co-culturing with thymocytes at relative concentrations of 10(4) and 10(7) cells per ml. Thymocyte viability was important for inducing the stimulatory effect. The effect of viable cells could not be replaced by their supernatant. Stimulatory activity of CD4(-)CD8(-) and CD4(+)CD8(+) thymocytes was comparable, alpha1-thymosin and some of its synthetic fragments did not influence alpha1-thymosin synthesis or slightly inhibited it (in high concentrations). Synthetic peptide corresponding to C-terminal half of alpha1-thymosin molecule strongly enhanced production of this hormone.

  16. Total synthesis of the α-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone.

    Science.gov (United States)

    Aussedat, Baptiste; Fasching, Bernhard; Johnston, Eric; Sane, Neeraj; Nagorny, Pavel; Danishefsky, Samuel J

    2012-02-22

    Described herein is the first total chemical synthesis of the unique α-subunit of the human glycoprotein hormone (α-hGPH). Unlike the biologically derived glycoprotein hormones, which are isolated as highly complex mixtures of glycoforms, α-hGPH obtained by chemical synthesis contains discrete homogeneous glycoforms. Two such systems have been prepared. One contains the disaccharide chitobiose at the natural N-glycosylation sites. The other contains dodecamer oligosaccharides at these same sites. The dodecamer sugar is a consensus sequence incorporating the key features associated with human glycoproteins.

  17. Human growth hormone binding and stimulation of insulin biosynthesis in cloned rat insulinoma cells

    DEFF Research Database (Denmark)

    Billestrup, Nils

    1985-01-01

    Binding of 125I labelled human growth hormone to cloned insulin producing RIN-5AH cells is described. Binding was specific for somatotropic hormones since both human and rat growth hormone could compete for binding sites, whereas much higher concentrations of lactogenic hormones were needed...

  18. Human Growth Hormone (HGH): Does It Slow Aging?

    Science.gov (United States)

    Healthy Lifestyle Healthy aging Human growth hormone is described by some as the key to slowing the aging process. Before you sign up, get the facts. ... stave off some of the changes linked to aging, such as decreased muscle and bone mass. If ...

  19. Human growth hormone alters carbohydrate storage in blood and ...

    African Journals Online (AJOL)

    MJP

    2015-06-02

    Jun 2, 2015 ... ... which permits unrestricted use, distribution, and reproduction in any medium, provided the ... of granivorous species, such as the chicken ... dominant in carnivorous avian species.[1] The ... Studies in humans and animal models show ..... rabbits over expressing growth hormone develop acromegaly and.

  20. Sex hormones and the immune response in humans

    NARCIS (Netherlands)

    Bouman, Annechien; Heineman, Maas Jan; Faas, Marijke M.

    2005-01-01

    In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more

  1. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  2. Thyroid hormone effect on human mitochondria measured by flow cytometry

    DEFF Research Database (Denmark)

    Kvetny, Jan; Bomholt, Tobias; Pedersen, Palle

    2009-01-01

    BACKGROUND: Mitochondrial function may be impaired in a number of diseases including metabolic syndrome, cardiovascular disease and endocrine disorders. Therefore it is important to be able to measure mitochondrial function in human cells. PURPOSE: The aim of the present study was to evaluate...... a method to measure mitochondrial function in human derived cells, which also would reflect regulation by thyroid hormones. METHODS: The MDA-MB-231 cell line (a human breast cancer cell line) was incubated with bioactive iodothyronines (T(4), 3'-3, 5-T(3), 3, 5-T(2)) 50 nmol/l for 3 h. Mitochondrial......: It was possible to measure mitochondrial membrane potential (MMP) in human derived cells and to examine thyroid hormone effects using flow cytometry. Bioactive iodothyronines increased mitochondrial membrane potential. TRIAC had no effect and L-Carnitine only inhibited T(4) stimulation of membrane potential...

  3. [How safe is the recombinant human growth hormone?

    Science.gov (United States)

    Calzada-León, Raúl

    2017-01-01

    In this paper, several aspects related to the safety of the use of biosynthetic human growth hormone are reviewed. For example, its classification as a biosynthetic drug, the phases that need to be performed in Mexico to verify its safety (obtaining, purification, preclinical studies, clinical trials, and finally observational clinical studies), as well as the evidence that exists in relation to the association of intracranial hypertension, muscular events, scoliosis, slipped capital femoral epiphysis, obstructive sleep apnea, pancreatitis, alterations in cortisol, thyroid hormones alterations, cardiovascular disease, metabolic risk, mortality and cancer, adverse events not related to its use, and finally dosing and safety.

  4. Thyroid-stimulating immunoglobulins in Hashimoto's thyroiditis measured by radioreceptor assay and adenylate cyclase stimulation and their relationship to HLA-D alleles

    Energy Technology Data Exchange (ETDEWEB)

    Bliddal, H. (Frederiksberg Hospital, Copenhagen, Denmark); Bech, K.; Feldt-Rasmussen, U.; Thomsen, M.; Ryder, L.P.; Hansen, J.M.; Siersbaek-Nielsen, K.; Friis, T.

    1982-11-01

    The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto's thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was found in 1 subject, compared to 8 of the 20 HTACS-negative patients (P < 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = 0.09).No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded that TBII and HTACS are produced independently in Hashimoto's thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.

  5. A method for identification of the peptides that bind to a clone of thyroid-stimulating antibodies in the serum of Graves' disease patients.

    Science.gov (United States)

    Na, Chan Hyun; Lee, Mi Hwa; Cho, Bo Youn; Chae, Chi-Bom

    2003-04-01

    A method was developed for identification of the peptide sequences that bind to thyroid-stimulating antibody (TSAb) clones from phage-displayed peptide library. Immunoglobulin G (IgG) was purified from the serum of a Graves' disease patient that stimulates the synthesis of cAMP in the cells that express TSH receptor (TSHR). The IgG that binds to TSHR was purified by an affinity column packed with the resin cross-linked with the extracellular domain of human TSHR. The receptor-binding IgG was then mixed with phages that display linear or cyclic peptides at the end of tail protein pIII. The bound phages were eluted with acidic glycine after extensive washing. From sequencing of the pIII gene of the bound phages, one can deduce the sequences of the peptides that bind to the receptor-binding IgG. Each peptide sequence was then tested for inhibition of the synthesis of cAMP from thyroid cells induced by the serum of a Graves' patient. In this way, one can obtain the peptides that bind to a clone of TSAb. We obtained a peptide sequence that inhibits the action of TSAb at an extremely low concentration (<10(-14) M). Such a peptide will be useful for various studies on TSAb.

  6. Minireview: Hormones and Human Sexual Orientation

    OpenAIRE

    Balthazart, Jacques

    2011-01-01

    Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa). In animals and men, many sexually differentiated characteristics are organized during early life by sex...

  7. EFFECTS OF CHINA-MADE RECOMBINANT HUMAN GROWTH HORMONE ON THE TREATMENT OF GROWTH HORMONE DEFICIENCY

    Institute of Scientific and Technical Information of China (English)

    Jing Jiang; Wei Wang; Wen-xin Sun; Xiu-min Wang; Ji-hong Ni; Feng-sheng Chen; De-fen Wang

    2004-01-01

    Objective To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment.Methods Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment.Results After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 + 3.7 and 12.6 ± 3.6 cm/year) compared with pretreatment values (2.9 ± 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls(P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01).Conclusions (1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.

  8. Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes.

    Science.gov (United States)

    Zouboulis, Christos C; Seltmann, Holger; Hiroi, Naoki; Chen, WenChieh; Young, Maggie; Oeff, Marina; Scherbaum, Werner A; Orfanos, Constantin E; McCann, Samuel M; Bornstein, Stefan R

    2002-05-14

    Sebaceous glands may be involved in a pathway conceptually similar to that of the hypothalamic-pituitary-adrenal (HPA) axis. Such a pathway has been described and may occur in human skin and lately in the sebaceous glands because they express neuropeptide receptors. Corticotropin-releasing hormone (CRH) is the most proximal element of the HPA axis, and it acts as central coordinator for neuroendocrine and behavioral responses to stress. To further examine the probability of an HPA equivalent pathway, we investigated the expression of CRH, CRH-binding protein (CRH-BP), and CRH receptors (CRH-R) in SZ95 sebocytes in vitro and their regulation by CRH and several other hormones. CRH, CRH-BP, CRH-R1, and CRH-R2 were detectable in SZ95 sebocytes at the mRNA and protein levels: CRH-R1 was the predominant type (CRH-R1/CRH-R2 = 2). CRH was biologically active on human sebocytes: it induced biphasic increase in synthesis of sebaceous lipids with a maximum stimulation at 10(-7) M and up-regulated mRNA levels of 3 beta- hydroxysteroid dehydrogenase/Delta(5-4) isomerase, although it did not affect cell viability, cell proliferation, or IL-1 beta-induced IL-8 release. CRH, dehydroepiandrosterone, and 17 beta-estradiol did not modulate CRH-R expression, whereas testosterone at 10(-7) M down-regulated CRH-R1 and CRH-R2 mRNA expression at 6 to 24 h, and growth hormone (GH) switched CRH-R1 mRNA expression to CRH-R2 at 24 h. Based on these findings, CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induce CRH negative feedback. The findings implicate CRH in the clinical development of acne, seborrhea, androgenetic alopecia, skin aging, xerosis, and other skin disorders associated with alterations in lipid formation of sebaceous origin.

  9. Ovarian response to recombinant human follicle-stimulating hormone

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; Andersen, Anders Nyboe; Fernández-Sánchez, Manuel

    2014-01-01

    OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrat......OBJECTIVE: To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH......) concentrations. DESIGN: Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-infertility centers in four countries. PATIENT(S): Two hundred sixty-five women aged ≤37 years. INTERVENTION(S): Controlled...

  10. Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure

    OpenAIRE

    Kucuk, Nurten; Sari, Murat; Midi, Ahmet; Yumusakhuylu, Ali Cemal; Findik, Ozan; Binnetoglu, Adem

    2015-01-01

    Objectives In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase i...

  11. Electrochemical Methods for Human Growth Hormone Doping Detection

    OpenAIRE

    2015-01-01

    Human Growth Hormone (GH) is produced by the anterior pituitary gland and promotes growth of tissue through direct uptake at target tissue sites, or alternatively, by regulating production of insulin-like growth factor-1. The World Anti-Doping Agency considers GH a performance enhancing substance, so the use of GH by athletes is prohibited in most sports. The current immunoassay for GH detection is suboptimal for routine screening of blood samples because of the large resources required for c...

  12. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ramasharma, K.; Li, C.H.

    1987-05-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and ..cap alpha..-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin.

  13. Is there a hormonal basis for human homosexuality?

    Institute of Scientific and Technical Information of China (English)

    Louis Gooren

    2011-01-01

    In the August 2011 issue of Endocrinology,Dr Balthazart presents a minireview on Hormones and Human Sexual Orientation.1As in most scientific papers on this issue,the contribution lacks an operational definition of (human) homosexuality.Personally,I like the definition of John Money.2 ‘Homosexuality is characterized by same-sex contact,either as a genital act or as a long-term sexual/erotic status.A homosexual person is able to fall in love with,and become the pairbonded sexual/erotic partner of only a person of the same morphological sex'.

  14. Recombinant human growth hormone in the treatment of Turner syndrome

    Directory of Open Access Journals (Sweden)

    Bessie E Spiliotis

    2008-12-01

    Full Text Available Bessie E SpiliotisDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Patras, School of Medicine, Patras, GreeceAbstract: Turner syndrome (TS is a common chromosomal disorder in women that is associated with the absence of one of the X chromosomes. Severe short stature and a lack of pubertal development characterize TS girls, causing psychosocial problems and reduced bone mass. The growth impairment in TS seems to be due to multiple factors including an abnormal growth hormone (GH – insulin-like growth factor (IGF – IGF binding protein axis and haploinsufficiency of the short stature homeobox-containing gene. Growth hormone and sex steroid replacement therapy has enhanced growth, pubertal development, bone mass, and the quality of life of TS girls. Recombinant human GH (hGH has improved the height potential of TS girls with varied results though, depending upon the dose of hGH and the age of induction of puberty. The best final adult height and peak bone mass achievement results seem to be achieved when hGH therapy is started early and puberty is induced at the normal age of puberty in a regimen mimicking physiologic puberty. The initiation of estradiol therapy at an age-appropriate time may also help the TS patients avoid osteoporosis during adulthood. Recombinant hGH therapy in TS seems to be safe. Studies so far show no adverse effects on cardiac function, glucose metabolism or any association with neoplasms but research is still in progress to provide conclusive data on long-term safety.Keywords: Turner syndrome, recombinant growth hormone, growth hormone deficiency, SHOX gene, hormonal replacement therapy

  15. Sex hormone effects on autonomic mechanisms of thermoregulation in humans.

    Science.gov (United States)

    Charkoudian, Nisha; Stachenfeld, Nina

    2016-04-01

    Autonomic mechanisms are fundamental to human physiological thermoregulation, and female reproductive hormones have substantial influences on several aspects of these mechanisms. Of these, the best recognized are the thermoregulatory responses that occur at menopause (hot flushes) and the changes in body temperature within the menstrual cycle which may help couples predict ovulation. Our goal in this brief review is to summarize current knowledge regarding the influences of reproductive hormones on autonomic mechanisms in human thermoregulation. In general, estrogens tend to promote lower body temperatures via augmentation of heat dissipation responses, whereas progesterone tends to promote higher body temperatures. Recent evidence suggests specific influences of estrogens on central autonomic nuclei involved in control of skin blood flow and sweating. Estrogens also augment vasodilation by direct effects on peripheral blood vessels. Influences of progesterone are less well understood, but include both centrally regulated changes in thermoregulatory set-point as well as and peripheral effects, including augmented vasoconstriction in the skin. We conclude with a brief discussion of thermoregulatory adjustments associated with changing hormone levels during menopause, pregnancy and polycystic ovary syndrome. Published by Elsevier B.V.

  16. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  17. Effects of aging on thermoregulatory responses and hormonal changes in humans during the four seasons in Japan

    Science.gov (United States)

    Sato, Maki; Kanikowska, Dominika; Sugenoya, Junichi; Inukai, Yoko; Shimizu, Yuuki; Nishimura, Naoki; Iwase, Satoshi

    2011-03-01

    Physiological functions are impaired in various organs in aged people, as manifest by, e.g., renal and cardiac dysfunction and muscle atrophy. The elderly are also at increased risk of both hypothermia and hyperthermia in extreme temperatures. The majority of those over 65 years old have elevated serum osmolality. Our hypothesis is that the elderly have suppressed osmolality control in different seasons compared to the young. Eight healthy young men and six healthy older men participated in this study. The experiments were performed during spring, summer, autumn and winter in Japan, with average atmospheric temperatures of 15-20°C in spring, 25-30°C in summer, 15-23°C in autumn and 5-10°C in winter. Each subject immersed his lower legs in warm water at 40°C for 30 min. Core (tympanic) temperature and sweat rate at chest were recorded continuously. Blood was taken pre-immersion to measure the concentrations of antidiuretic hormone, serum osmolality, plasma renin activity, angiotensin II, aldosterone, leptin, thyroid stimulating hormone, fT3 and fT4. The results suggested that the elderly have suppressed osmolality control compared to the young; osmolality was especially elevated in winter compared to the summer in elderly subjects. Therefore, particularly in the elderly, balancing fluid by drinking water should be encouraged to maintain euhydration status in winter.

  18. Luteinizing hormone and human chorionic gonadotropin: origins of difference.

    Science.gov (United States)

    Choi, Janet; Smitz, Johan

    2014-03-01

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy. Aside from the timing of expression, however, the differences between LH and hCG have largely been overlooked in the clinical realm because of their similar molecular structures and shared receptor. With technologic advancements, including the development of highly purified and recombinant gonadotropins, researchers now appreciate that these hormones are not as interchangeable as once believed. Although they bind to a common receptor, emerging evidence suggests that LH and hCG have disparate effects on downstream signaling cascades. Increased understanding of the inherent differences between LH and hCG will foster more effective diagnostic and prognostic assays for use in a variety of clinical contexts and support the individualization of treatment strategies for conditions such as infertility.

  19. Polyethylene glycol method is superior to ammonium sulfate and protein-A sepharose-4B method in fractionating thyroid stimulating immunoglobulin in Graves' disease.

    Science.gov (United States)

    Jap, T S; Jenq, S F; Wong, M C; Chiang, H

    1995-03-01

    The purpose of this study is to compare the performance of three methods, i.e., ammonium sulfate, polyethylene glycol (PEG) and protein A sepharose 4B in fractionation of thyroid stimulating immunoglobulin. Twelve patients with Graves' disease and twelve age-, sex-matched normal controls were recruited. 0.9 ml of saturated ammonium sulfate was added slowly to 1.1 ml of sera of all subjects and was stirred until reaching 45% saturation. The precipitation was allowed to form at 4 degrees C overnight. The solution was centrifuged at 10,000 x g for 5 minutes. The precipitate was washed twice with 45% ammonium sulfate, dissolved in 0.55 ml of distilled water equal to half of the initial volume of the serum and dialyzed against 200 volumes of phosphate-buffered saline (PBS) for 48 hours. Another 0.5 ml of serum sample from the same patients was mixed with 1.5 ml of 20% polyethylene, followed by centrifugation at 2,800 g for 20 minutes. The pellet was dissolved in 0.6 ml of Hanks' medium without NaCl containing 1.5% bovine serum albumin, 20mM HEPES: 1 ml of sera was applied to 0.75 g of protein A sepharose-4B in PBS buffer and eluted with glycine, pH 2.3. By adding immunoglobulin (Ig) from the different methods to the FRTL-5 tissue culture, we determined the cAMP generation. Patients with Graves' disease were found to have higher serum thyroxine and triiodothyronine concentrations (p TSI) while with ammonium sulfate precipitation, nine out 12 patients (75%) showed positive TSI. On the other hand, all patients showed positive TSI with PEG precipitation. When the degree of thyrotoxicosis was classified in terms of thyroid hormone concentrations, there was no correlation between TSI titers and thyroid hormone concentration. Polyethylene glycol is superior to both ammonium sulfate and protein A sepharose-4B in fractionating TSI in terms of sensitivity and convenience in operation.

  20. Shaped and Balanced by Hormones : cortisol, testosterone and the psychoneuroendocrinology of human socio-emotional behavior

    NARCIS (Netherlands)

    Montoya, E.R.

    2015-01-01

    The steroid hormones testosterone and cortisol can be considered hormones for environmental challenges; they are involved in adaptive neural and behavioral responses towards emotional stimuli. A key challenge of human psychoneuroendocrinology is to unravel the neural mechanisms by which testosterone

  1. Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

    DEFF Research Database (Denmark)

    Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S;

    2009-01-01

    relationship and derivation from a single precursor B-cell clone. The IGHV-region genes of the two mAbs underwent high degrees of somatic hypermutation by sharing numerous mutations before diverging, while the IGLV genes evolved separately. Interestingly, the mutations were present in both the complementarity......-determining regions (CDRs) and the framework regions. The cloned IGHV and IGLV genes were confirmed to have TSAb properties in experiments in which they were expressed as recombinant Fabs (rFabs). In other experiments, we swapped the IGLV genes with IGHV genes by constructing chimeric rFabs and showed...... that the chimeras retained TSAb activities, confirming the close functional relatedness of the V-region genes. Importantly, the IGLV genes in chimeric rFabs had a dominant stimulatory effect at low concentrations, while the IGHV genes had a dominant effect at higher concentrations. Our findings demonstrate that...

  2. Physico-chemical characterization of human recombinant follicle-stimulating hormone (hFSH) and its subunits by reversed-phase high-performance liquid chromatography ( RP-HPLC): comparison with pituitary hFSH reference preparation from 'National Hormone and Pituitary Program' from USA; Caracterizacao fisico-quimica da foliculotropina humana(hFSH) recombinabte e de suas subunidades, por cromatografia liquida de alta eficiencia (HPLC) em fase reversa: comparacao com a preparacao de referencia de hFSH de origem hipofisaria do ''National Hormone and Pituitary Program'' dos EUA

    Energy Technology Data Exchange (ETDEWEB)

    Loureiro, Renan Fernandes

    2006-07-01

    A reversed-phase high-performance liquid chromatography (RP-HPLC) method for the qualitative and quantitative analysis of intact human folliclestimulating hormone (hFSH) was established and validated for accuracy, precision and sensitivity. Human FSH is a dimeric glycoprotein hormone widely used as a diagnostic analyte and as therapeutic product in reproductive medicine. The technique developed preserves the protein integrity, allowing the analysis of the intact heterodimeric form rather than just of its subunits, as it is the case for the majority of the conditions currently employed. This methodology has also been employed for comparing the relative hydrophobicity of pituitary, urinary and two Chinese hamster ovary (CHO)-derived hFSH preparations, as well as of two other related glycoprotein hormones of the anterior pituitary: human thyroid-stimulating hormone (hTSH) and human luteinizing hormone (hLH). The least hydrophobic of the three glycohormones analyzed was hFSH, followed by hTSH and hLH. A significant difference (p<0.005) was observed in t{sub R} between the pituitary and recombinant hFSH preparations, reflecting structural differences in their carbohydrate moieties. Two main isoforms were detected in urinary hFSH, including a form which was significantly different (p<0.005) for the pituitary and recombinant preparations. The linearity of the dose-response curve (r = 0.9965, n = 15) for this RP-HPLC methodology, as well as an inter-assay precision with relative standard deviation less than 4% for the quantification of different hFSH preparations and a sensitivity of the order of 40 ng, were demonstrated. The chromatographic behavior and relative hydrophobicity of the individual subunits of the pituitary and recombinant preparations were also analyzed. Furthermore, the accurate molecular mass of the individual hFSH subunits and of the heterodimer were simultaneously determined by matrix-assisted laser desorption ionization time-of-flight mass spectral

  3. Sleep deprivation alters thyroid hormone economy in rats.

    Science.gov (United States)

    Rodrigues, Nayana Coutinho; da Cruz, Natália Santos; de Paula Nascimento, Cristine; da Conceição, Rodrigo Rodrigues; da Silva, Alba Cenélia Matos; Olivares, Emerson Lopes; Marassi, Michelle Porto

    2015-02-01

    What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all

  4. "THE EFFECT OF HORMONAL AND NON-HORMONAL CONTRACEPTIVE METHODS ON THE ANTIOXIDANT CONTENT OF HUMAN MILK"

    Directory of Open Access Journals (Sweden)

    Sh. Khaghani

    2004-11-01

    Full Text Available Different contraceptive methods are used by breastfeeding mothers. In general, these methods are classified into two major groups, hormonal and non-hormonal. A number of studies have shown that combined oral contraceptive pills may adversely affect the quality and the quantity of human milk. In other studies it has been shown that estrogen and progesterone seem to reduce the risk of cardiac and ischemic brain injury by enhancing anti-oxidant mechanisms. Since infants are at increased risk of oxidative stress and free-radical mediated diseases are partly related to deficient antioxidant state, we performed a study to investigate if contraceptive method has any effect on the maternal milk total antioxidant content. A cross-sectional study of total antioxidant capacity of mature human milk of two groups of healthy breastfeeding mothers who were on the hormonal (Lynestrol or non-hormonal contraceptive regimen with 92 mothers in each group was performed. The total antioxidant capacity was determined by ferric reducing antioxidant power method. The body mass indexes (BMI of hormonal and non-hormonal groups were 23.67±2.88 and 22.93±3.33 kg/m2,respectively, with no significant difference. The hemoglobin concentrations of hormonal versus nonhormonal groups were 12.94±0.90 and 13.14± 0.76 g/dl which were not significantly different. The mean total antioxidant contents of the hormonal and non-hormonal groups were 575±139 and 583±135 µmol/l, respectively, with no significant difference. It seems that progesterone has no effect on the antioxidant contents of mature human milk; in other words, the Lynestrol has neither positive nor negative effect on the antioxidant capacity of the human milk.

  5. Algorithmic complexity of growth hormone release in humans.

    Science.gov (United States)

    Prank, K; Wagner, M; Brabant, G

    1997-01-01

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

  6. Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

    Science.gov (United States)

    Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

    1985-01-01

    The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

  7. Algorithmic complexity of growth hormone release in humans

    Energy Technology Data Exchange (ETDEWEB)

    Prank, K.; Wagner, M.; Brabant, G. [Medical School Hannover (Germany)

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  8. Studies on stabilities of some human chorionic gonadotropin complexes with {beta}-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, Moumita [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Sen, Kamalika [Department of Chemistry, University of Calcutta, 92 APC Road, Kolkata 700009 (India); Sen, Souvik [Malda Town Divisional Railway Hospital, Malda 732102 (India); Lahiri, Susanta, E-mail: susanta.lahiri@saha.ac.i [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India)

    2011-02-15

    Human chorionic gonadotropin (hCG) is a peptide hormone, whose one of the structural subunits is identical to that of thyroid-stimulating hormone (TSH). As a consequence, the receptors of TSH also act as receptor for hCG hormone. Keeping in mind this interesting property of hCG we have studied the complex formation ability of various no-carrier-added {beta}-emitting isotopes of {sup 61}Cu (3.3 h), {sup 62}Zn (9.2 h), {sup 90}Nb (14.60 h) and {sup 99}Mo (66.02 h) with hCG molecule. Stability of the hCG-M (M=metal ions) complexes was investigated by dialysis with respect to triple distilled water and ringer lactate solution, which has the same composition as extracellular fluid.

  9. Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans

    Directory of Open Access Journals (Sweden)

    Joanne L. Calley

    2014-01-01

    Full Text Available The kisspeptins are a family of neuropeptides which act as upstream stimulators of gonadotrophin releasing hormone (GnRH neurons. Kisspeptin signalling is prerequisite to establishing the normal human reproductive phenotype; loss of function mutations in the KISS1 or KISS1R gene produces normosmic hypogonadotrophic hypogonadism in humans and mice, whilst increased activation of KISS1R causes precocious puberty. Administration of exogenous kisspeptin to human subjects stimulates an acute gonadotrophin rise. Serum kisspeptin levels also markedly increase during pregnancy. The identification of kisspeptin has been one of the biggest discoveries in the field of reproductive endocrinology, since the isolation and sequencing of GnRH in 1977, and has generated a novel research avenue which has received much attention over the past decade. This research has delineated many properties of the KISS1-KISS1R system, but there is still further work to do. Understanding kisspeptin’s role throughout our reproductive lifetime should help us better understand—and therefore treat—disorders of reproductive function. Promisingly, the current data supports the potential to develop kisspeptin based therapies. As an outlook article this paper focusses predominantly on our groups recent investigations into the effects of kisspeptin administration to humans and the potential therapeutic role of kisspeptin.

  10. Expression of Thyroid Hormone Transporters in the Human Hypothalamus

    NARCIS (Netherlands)

    A. Alkemade; E.C.H. Friesema; A. Kalsbeek; D.F. Swaab; T.J. Visser; E. Fliers

    2011-01-01

    Context: Transport of thyroid hormone across the plasma membrane is required for proper thyroid hormone action and metabolism. Several specific thyroid hormone transporters have been identified capable of facilitating uptake and/or efflux of thyroid hormones. Monocarboxylate transporter (MCT)-8, MCT

  11. Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study

    Science.gov (United States)

    Yang, Lin; Li, Jingguang; Lai, Jianqiang; Luan, Hemi; Cai, Zongwei; Wang, Yibaina; Zhao, Yunfeng; Wu, Yongning

    2016-02-01

    Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = -0.261 to -0.170, all P fetal PFASs (r = -0.229 to -0.165 for T3; r = -0.293 to -0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans.

  12. Dissociation of human follicle-stimulating hormone. Comparison with luteinizing hormone.

    Science.gov (United States)

    Reichert, L E; Ramsey, R B

    1975-04-25

    Rat testis tissue receptor assays were utilized to study the kinetics of dissociation of human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) under varying conditions of urea concentration and pH. In these competitive protein binding assays, 125I-hFSH and 125I-hLH were the radioligands and hormone dissociation was followed by a decrease in the ability of the dissociating hormone to inhibit uptake of the radioligand by tissue receptors. Rate data for dissociation of the gonadotropins were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. Treatment of hFSH with 4 M urea at pH 8 and 25 degrees for 22 hours did not result in significant dissociation, whereas in 8 M urea, over 90% dissociation was observed. The rate of dissociation of hFSH in 8 M urea was increased approximately 4-fold by raising the temperature from 25 to 37 degrees. Similar results were obtained when dissociation of hFSH was followed through use of an accepted whole animal bioassay for FSH, thus confirming the reliability of the tissue receptor assay for such dissociation studies. Kinetic studies showed that hFSH was undissociated by incubation in 6 M urea of pH 8 after 4 hours at 25 degrees. In contrast, hLH was 90% dissociated under similar conditions. This differential rate of inactivation of hLH allowed preparation of hFSH having significant reduced levels of contaminating LH activity, as determined by tissue receptor assays and by whole animal bioassays. Marked differences were noted in the rate of dissociation of hFSH and hLH under acid conditions. hFSH completely dissociated after approximately 2 min of incubation of pH 2 (25 degrees), and over 90% dissociated after 15 min of incubation at pH 3. In contrast, hLH was dissociated 60% after 20 min of incubation at pH 2 (25 degrees) and 40% dissociated after 60 min at pH 3. Neither hormone was significantly dissociated at pH 4.4 after 60 min, but hFSH showed a

  13. Role of maternal thyroid hormones in the developing neocortex and during human evolution

    Directory of Open Access Journals (Sweden)

    Denise eStenzel

    2013-07-01

    Full Text Available The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g. caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors, even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of thyroid hormone receptors and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones.

  14. Role of maternal thyroid hormones in the developing neocortex and during human evolution.

    Science.gov (United States)

    Stenzel, Denise; Huttner, Wieland B

    2013-01-01

    The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones.

  15. Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans

    Science.gov (United States)

    After a short-term fast, lactating women have increased rates of glucose production but not gluconeogenesis (GNG) despite relative hypoinsulinemia. We explored the effects of non-insulin-dependent increase in glucose utilization and recombinant human growth hormone (rhGH) on glucose production, glyc...

  16. Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study

    Directory of Open Access Journals (Sweden)

    E. Kampmann

    2015-01-01

    Full Text Available The clinical utility of the functional TSH receptor autoantibodies was prospectively evaluated in patients with thyroid-associated orbitopathy (TAO. Ophthalmic, endocrine, and serological investigations were performed in 101 consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb and blocking (TBAb antibody levels were measured with two bioassays using cells that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results are expressed as percentage of specimen-to-reference ratio (SRR %. Blocking activity is defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone. All 101 consecutively followed-up patients with severe and active TAO were TBAb negative. In contrast, 91 (90% were TSAb positive of whom 90 had Graves’ disease. Serum TSAb levels correlated with the diplopia score (P=0.016, total severity eye score (P=0.009, proptosis (P=0.007, lid aperture (P=0.003, upper lid retraction (P=0.006, keratopathy (P=0.04, and thyroid binding inhibiting immunoglobulins (TBII, P<0.001 and negatively with the duration of TAO (P=0.002. Median serum values of TSAb were SRR% 418 (range 28% to 795%. TSAb, not TBAb, are highly prevalent in severe/active TAO and serum TSAb levels correlate with clinical disease severity.

  17. Thyroxine modifies the effects of growth hormone in Ames dwarf mice

    OpenAIRE

    Do, Andrew; Menon, Vinal; Zhi, Xu; Gesing, Adam; Wiesenborn, Denise S.; Spong, Adam; Sun, Liou; Bartke, Andrzej; Masternak, Michal M.

    2015-01-01

    Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early‐life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment ...

  18. Growth Hormone

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Growth Hormone Share this page: Was this page helpful? Also known as: GH; Human Growth Hormone; HGH; Somatotropin; Growth Hormone Stimulation Test; Growth ...

  19. Examining recombinant human TSH primed {sup 131}I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol

    Energy Technology Data Exchange (ETDEWEB)

    Rani, Deepa; Kaisar, Sushma; Awasare, Sushma; Kamaldeep; Abhyankar, Amit; Basu, Sandip [Bhabha Atomic Research Centre (BARC), Radiation Medicine Centre, Mumbai (India)

    2014-09-15

    Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is a promising recent development in the management of differentiated thyroid carcinoma (DTC). The objectives of this prospective study were: (1) to assess the feasibility and efficacy of the rhTSH primed {sup 131}I therapy protocol in patients with DTC with distant metastatic disease, (2) to perform lesional dosimetry in this group of patients compared to the traditional protocol, (3) to document the practical advantages (patient symptoms and hospital stay) of the rhTSH protocol compared to the traditional thyroid hormone withdrawal protocol, (4) to document and record any adverse effect of this strategy, (5) to compare the renal function parameters, and (6) to compare the serum TSH values achieved in either of the protocols in this group of patients. The study included 37 patients with metastatic DTC having lung or skeletal metastases or both. A comparison of lesional radiation absorbed dose, hospital stay, renal function tests, and symptom profile was undertaken between the traditional thyroid hormone withdrawal protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic lesions were performed using lesion uptake and survey meter readings for calculation of effective half-life. Non-contrast-enhanced CT was used for assessment of tumor volume. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG level 3 months after treatment. The mean effective half-life of {sup 131}I in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to the thyroid hormone withdrawal protocol (35.48 h), but the difference was not statistically significant (p = 0.056). The mean 24-h % uptake of the lesions during the traditional protocol (4.84 %) was slightly higher than the 24-h % uptake during the rhTSH protocol (3.56 %), but

  20. Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

    Science.gov (United States)

    Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

    2001-12-01

    Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

  1. Development of a long acting human growth hormone analog suitable for once a week dosing.

    Science.gov (United States)

    Palanki, Moorthy S S; Bhat, Abhijit; Bolanos, Ben; Brunel, Florence; Del Rosario, Joselyn; Dettling, Danielle; Horn, Mark; Lappe, Rodney; Preston, Ryan; Sievers, Annette; Stankovic, Nebojsa; Woodnut, Gary; Chen, Gang

    2013-01-15

    Human growth hormone was conjugated to a carrier aldolase antibody, using a novel linker by connecting a disulphide bond in growth hormone to a lysine-94 amine located on the Fab arm of the antibody. The resulting CovX body showed reduced affinity towards human growth hormone receptor, reduced cell-based activity, but improved pharmacodynamic properties. We have demonstrated that this CovX-body, given once a week, showed comparable activity as growth hormone given daily in an in vivo hypophysectomized rat model.

  2. Expression of Obesity Hormone Leptin in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Jin-chun Cong; Xian-wei Dai; Ming-yang Shen; Jun-jiang Wang; Chun-sheng Chen; Hong Zhang; Lei Qiao

    2009-01-01

    Objective: The obesity hormone, leptin, has been found to participate in the development and proliferation of normal and malignant tissues. The aim of this study was to evaluate the role of leptin in human colorectal cancer.Methods: Serum leptin levels were measured via ABC-ELLSA in 30 colorectal cancers and 24 normal controls. Leptin concentration in colorectal cancer was analyzed in terms of selected clinicopathological features and some oncogenes.Results: The mean concentration of leptin was significantly higher for colorectal cancers(3.54±1.46 ng/ml) than normal controls(2.27±0.99 ng/ml), no gender difference was observed in this study. Leptin expression in poorly differentiated tumors was obviously lower than those in moderately and well differentiated tumors. There were no statistically significant correlations between leptin and the serum CEA and CA199 in colorectal cancers (P>0.05), and between leptin and the expressions of K-RAS, P53, APC, DCC genes in tumor tissues (P>0.05).Conclusion: Leptin is overexpressed in human colorectal cancer, which is related to the differentiation degrees of the tumor. There is no correlation between leptin expression and chages of oncogenes in colorectal cancers.

  3. Buccal adhesive nanofibers containing human growth hormone for oral mucositis.

    Science.gov (United States)

    Choi, Ji Suk; Han, Suk-Hee; Hyun, Changbaig; Yoo, Hyuk Sang

    2016-10-01

    Due to a lack of proper drug carriers to deliver treatments for mucositis, many cancer patients suffer from oral mucositis caused by chemotherapy and radiotherapy. We prepared a double-layered electrospun nanofibrous sheets composed of Eudragit and chitosan to accelerate the healing rate of oral mucous ulcer. Human growth hormone (hGH) and Eudragit in a mixture of dimethylacetamide and ethanol were co-electrospun to nanofibrous sheets. The electrospun fibrous mat was subsequently layered with chitosan by a dip-coating method. Chitosan-layered sheets showed attenuated mass erosion while uncoated sheets were instantly melted at the physiological condition. The released hGH was trapped on the chitosan layer by the ionic interaction between positively charged chitosan and negatively charged hGH, and a large number of entrapped proteins remained on the SIS membrane due to the muco-adhesive properties of chitosan. hGH-incorporated sheets significantly increased proliferation of human dermal fibroblasts. In vivo study employing oral ulcers in dogs, the ulcers dressed with chitosan-layered sheets showed enhanced wound recovery and the chitosan layers on the sheet greatly assisted prolonged recovery. Therefore, chitosan-layered Eudragit nanofibrous sheets can be potentially applied to developing muco-adhesive wound dressing materials with pH-dependent drug release by adjusting the thickness of chitosan sheath on the sheets. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1396-1406, 2016.

  4. Secretion of human parathyroid hormone from rat pituitary cells infected with a recombinant retrovirus encoding preproparathyroid hormone.

    OpenAIRE

    Hellerman, J G; Cone, R C; Potts, J. T.; Rich, A; Mulligan, R C; Kronenberg, H M

    1984-01-01

    In order to study the functions of precursors to secreted proteins, we expressed cloned DNA encoding human preproparathyroid hormone (preproPTH) in rat pituitary cells. We first constructed a recombinant plasmid containing human preproPTH cDNA and retroviral control signals. This recombinant plasmid was transfected into psi-2 cells, a packaging cell line that produces Moloney murine leukemia viral particles containing no retroviral RNA. The transfected psi-2 cells generated helper-free recomb...

  5. Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-12-01

    Full Text Available Ling Hou,1,* Zhi-hang Chen,2,* Dong Liu,3 Yuan-guo Cheng,2 Xiao-ping Luo1 1Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Pharmacy, Beijing Institute of Microbiology and Epidemiology, Beijing, 3Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this study Objective: Recombinant human growth hormone (rhGH replacement therapy in children generally requires daily subcutaneous (sc injections, which may be inconvenient for patients. Jintrolong® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong® vs daily doses of rhGH. Design and methods: Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong® at 0.2 mg/kg/w. Results: In comparison with rhGH, sc injection of Jintrolong® produced a noticeably higher Cmax, significantly longer half-life (t1/2, and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC after the seventh and first injections (AUC(0–∞7th/AUC(0–∞1st of rhGH was 1.02, while the AUC(0–∞6th/AUC(0–∞1st of Jintrolong® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong® injections. There were no severe adverse events during the trial. Conclusion: The elimination rate of Jintrolong® was

  6. Associations between brominated flame retardants in house dust and hormone levels in men

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Paula I. [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Stapleton, Heather M. [Nicholas School of the Environment, Box 90328, Duke University, Durham, NC 27708 (United States); Mukherjee, Bhramar [Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Hauser, Russ [Department of Environmental Health, Harvard School of Public Health, 677 Huntington Ave., Boston, MA 02115 (United States); Meeker, John D., E-mail: meekerj@umich.edu [Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109 (United States)

    2013-02-15

    Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octa- and deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men. - Highlights: ► Brominated flame retardants (BFRs) including PBDEs and alternates were measured. ► Exposure to BFRs is characterized from concentrations in participant vacuum bag dust. ► Exposure to PBDEs and

  7. Hormones and endocrine disruptors in human seminal plasma.

    Science.gov (United States)

    Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

    2013-07-01

    Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

  8. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.

    Science.gov (United States)

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs.

  9. Triiodothyronine inhibits transcription from the human growth hormone promoter.

    Science.gov (United States)

    Morin, A; Louette, J; Voz, M L; Tixier-Vidal, A; Belayew, A; Martial, J A

    1990-07-09

    Three DNA constructs, the natural human growth hormone gene (hGH-hGH) its 500 bp promoter linked to the chloramphenicol acetyl transferase reporter gene (hGH-CAT), and its structural part linked to the herpes virus thymidine kinase promoter (TK-hGH) were introduced into rat pituitary GC cells by DEAE-dextran transfection. Transient expression was followed as a function of triiodothyronine (T3) concentration. The hGH-CAT expression was specifically inhibited by T3 following a typical dose-response curve while hGH-GH gene expression was not significantly modified. The transient expression of TK-hGH increased as a function of T3 concentration. These results indicate that T3 exerts two opposite effects on hGH gene expression. First, it down-regulates expression by acting on the promoter; second, it up-regulates expression by acting on the structural part of the gene. These action could be due to regulation of transcription and mRNA stabilization, respectively.

  10. Polyacrylamide gels with selective recognition of the tetrameric molecular form of human growth hormone

    Directory of Open Access Journals (Sweden)

    R. Kublickas

    2017-08-01

    Full Text Available Networks of polyacrylamide were studied for the possibility of imprinting of the oligomeric form of human growth hormone. The tetrameric molecular form of human growth hormone was molecularly imprinted for the first time. The results show that approximately 50–70% (w/w of the templates (depending on polymerization conditions could be extracted from the molecularly imprinted acrylamide polymers. The resulting ‘gel antibodies’ against this form of human growth hormone in the form of granules of polyacrylamide were compared with granules of non-imprinted polymer. The selectivity of the artificial gel antibodies was studied. Investigation of the binding to imprinted polymer of the template hormone, other molecular forms of the hormone and other proteins shows the selectivity of the developed artificial gel antibodies.

  11. The role of thyroid hormone in sleep deprivation.

    Science.gov (United States)

    Pereira, José Carlos; Andersen, Mônica Levy

    2014-03-01

    Sleep deprivation is a stressful condition, as the subject experiences feelings of inadequate well-being and exhibits impairments in his/her functioning. However, in some circumstances sleep deprivation may be crucial for survival of the individual. Most likely, complex neural circuits and hormones play a role in allowing sleep deprivation to occur. For instance, thyroid hormone activity sharply increases when an individual is in a state of sleep deprivation. We believe that this increase is central to sleep deprivation physiology. During sleep deprivation, the hypothalamic-pituitary-thyroid axis initially increases as a consequence of increased release of thyroid stimulating hormone from the pituitary. Subsequently, as sleep deprivation continues, the sympathetic nervous system is recruited through its anatomical connection with the thyroid gland. While thyroid stimulating hormone levels markedly increase during sleep deprivation, it has been suggested that these increases are secondary to sleep deprivation. However, there is little evidence to support this assumption. We believe that the physiology of the thyroid axis during sleep deprivation and the actions of the effector hormone thyroid hormone suggest that thyroid hormone inhibits sleep and not the contrary. To our knowledge, few studies have addressed the possible neural functions that enable sleep deprivation. In this article, we discuss the hypothesis that an augmentation in the thyroid hormone axis is central to a subject's ability to curtail sleep.

  12. Expression of an Exogenous Growth Hormone Gene by Transplantable Human Epidermal Cells

    Science.gov (United States)

    Morgan, Jeffrey R.; Barrandon, Yann; Green, Howard; Mulligan, Richard C.

    1987-09-01

    Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.

  13. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  14. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-01-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development. PMID:28266608

  15. Investigations on hormone dependency of human mammary carcinomas transplanted into nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M

    1981-01-01

    Since human mammary cancer can be transplanted into nude mice, this makes possible the in vivo study of relations between hormone dependency and the steroid hormone receptor content of the tumors. The macroscopic growth curve of the transplanted tumors during endocrine therapy will reflect the ho...

  16. Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

    DEFF Research Database (Denmark)

    Veedfald, Simon; Plamboeck, Astrid; Deacon, Carolyn F

    2016-01-01

    Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 ...

  17. Inhibition effects of parathyroid hormone on human medullary thyroid carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yaqiong Ni; Qinjiang Liu; Shihong Ma; Ruihui Chen

    2014-01-01

    Objective:The purpose of the study was to investigate the ef ects of parathyroid hormone and parathyroid hor-mone receptor monoclonal antibody on in vitro growth and proliferation of human medul ary thyroid carcinoma celllines. Methods:The medul ary thyroid carcinoma cellline was cultured in vitro, with parathyroid hormone and parathyroid hormone receptor monoclonal antibody treatment intervention, the growth of the cells was observed under an inverted contrast micro-scope, the MTT assay was used to detect the cellgrowth inhibition rate. Results:Under the inverted contrast microscope, the cells changed significantly, the parathyroid hormone and parathyroid hormone receptor monoclonal antibodies can ef ectively inhibit the proliferation of medul ary thyroid cancer cells in a time and dose dependent. When parathyroid hormone concentra-tion reached a concentration of 2.0μmol/L, the parathyroid hormone receptor monoclonal antibody reached a concentration of 1.0μmol/L, the cellgrowth was most significantly inhibited (P<0.05). Conclusion:Parathyroid hormone and parathyroid hormone receptor monoclonal antibody were able to inhibit the proliferation of medul ary thyroid carcinoma cells and signifi-cantly reduce the proliferation index.

  18. Associations between brominated flame retardants in house dust and hormone levels in men

    Science.gov (United States)

    Johnson, Paula I.; Stapleton, Heather M.; Mukherjee, Bhramar; Hauser, Russ; Meeker, John D.

    2013-01-01

    Brominated flame retardants (BFRs) are used in the manufacture of a variety of materials and consumer products in order to meet fire safety standards. BFRs may persist in the environment and have been detected in wildlife, humans and indoor dust and air. Some BFRs have demonstrated endocrine and reproductive effects in animals, but human studies are limited. In this exploratory study, we measured serum hormone levels and flame retardant concentrations [31 polybrominated diphenyl ether (PBDE) congeners and 6 alternate flame retardants] in house dust from men recruited through a US infertility clinic. PBDE congeners in dust were grouped by commercial mixtures (i.e. penta-, octaand deca-BDE). In multivariable linear regression models adjusted by age and body mass index (BMI), significant positive associations were found between house dust concentrations of pentaBDEs and serum levels of free T4, total T3, estradiol, and sex hormone binding globulin (SHBG), along with an inverse association with follicle stimulating hormone (FSH). There were also positive associations of octaBDE concentrations with serum free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH) and testosterone and an inverse association of decaBDE concentrations with testosterone. Hexabromocyclododecane (HBCD) was associated with decreased SHBG and increased free androgen index. Dust concentrations of bis-tribromophenoxyethane (BTBPE) and tetrabromo-diethylhexylphthalate (TBPH) were positively associated with total T3. These findings are consistent with our previous report of associations between PBDEs (BDE 47, 99 and 100) in house dust and hormone levels in men, and further suggest that exposure to contaminants in indoor dust may be leading to endocrine disruption in men. PMID:23333513

  19. Gonadal hormone regulation of the emotion circuitry in humans

    NARCIS (Netherlands)

    Wingen, G.A. van; Ossewaarde, L.; Backstrom, T.; Hermans, E.J.; Fernandez, G.S.E.

    2011-01-01

    Gonadal hormones are known to influence the regulation of emotional responses and affective states. Whereas fluctuations in progesterone and estradiol are associated with increased vulnerability for mood disorders, testosterone is mainly associated with social dominance, aggressive, and antisocial b

  20. Estrogen inhibits corticotropin-releasing hormone production in primary human placental cells

    Institute of Scientific and Technical Information of China (English)

    唐晓露; 倪鑫; 由振东; 何平; 惠宁; 顾清; 孙刚

    2003-01-01

    Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete ER antagonist, and Tamoxifen, an ERα-mixed agonist/antagonist and ERβ antagonist for 24 h. The supernatant was havested for the radioimmunoassay of CRH. Results: 17β-estradiol inhibited the secretion of corticotropin-releasing hormone in human placental (P<0.05). ICI182, 780 stimulated the secretion of corticotropin-releasing hormone in human placental (P<0.05). Conclusion: Estrogen represses the synthesis and secretion of corticotropin-releasing hormone in human placental, which is possibly mediated by ERα.

  1. Both pituitary and placental growth hormone transcripts are expressed in human peripheral blood mononuclear cells (PBMC)

    NARCIS (Netherlands)

    Melen, L; Hennen, G; Dullaart, RPF; Igout, A

    1997-01-01

    The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered to be exclusively expressed in human placenta, where it replaces maternal circulating hGH-N at t

  2. Direct and in vitro observation of growth hormone receptor molecules in A549 human lung epithelial cells by nanodiamond labeling

    Science.gov (United States)

    Cheng, C.-Y.; Perevedentseva, E.; Tu, J.-S.; Chung, P.-H.; Cheng, C.-L.; Liu, K.-K.; Chao, J.-I.; Chen, P.-H.; Chang, C.-C.

    2007-04-01

    This letter presents direct observation of growth hormone receptor in one single cancer cell using nanodiamond-growth hormone complex as a specific probe. The interaction of surface growth hormone receptor of A549 human lung epithelial cells with growth hormone was observed using nanodiamond's unique spectroscopic signal via confocal Raman mapping. The growth hormone molecules were covalent conjugated to 100nm diameter carboxylated nanodiamonds, which can be recognized specifically by the growth hormone receptors of A549 cell. The Raman spectroscopic signal of diamond provides direct and in vitro observation of growth hormone receptors in physiology condition in a single cell level.

  3. Thyroid hormone disorders and sepsis.

    Science.gov (United States)

    Luo, Bin; Yu, Zhui; Li, Yinping

    2017-01-01

    Sepsis is a systemic inflammatory response syndrome with high mortality, which results from severe infection and can lead to secondary organ dysfunction. It is one of the most common cause of death in intensive care unit. Clinical reports have shown that sepsis was often accompanied by thyroid dysfunction, which is called "low triiodothyronine (T3)" syndrome and characterized by decreased blood total T3 and free T3, and by normal or decreased thyroxine (T4) and thyroid stimulating hormone (TSH). This syndrome may greatly affect the prognosis of patients with sepsis. The main purpose of this review is to illustrate the role of thyroid hormone disorder in the development and prognosis of sepsis.

  4. Optimization of production of recombinant human growth hormone in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Marzieh Rezaei

    2012-01-01

    Full Text Available Background: Human growth hormone (hGH is a single-chain polypeptide that participates in a wide range of biological functions such as metabolism of proteins, carbohydrates and lipids as well as in growth, development and immunity. Growth hormone deficiency in human occurs both in children and adults. The routine treatment for this condition is administration of recombinant human growth hormone (rhGH made by prokaryotes. Since nonglycosylated human growth hormone is a biologically active protein, prokaryotic expression systems are preferred for its production. Materials and Methods: Different strains of E.coli were transformed by plasmid containing human growth hormone gene and cultured in different conditions. After induction by IPTG, recombinant human growth hormone production was assessed using ELISA, dot blotting and western blotting techniques. Results: High levels of rhGH were produced using E.coli prokaryotic protein production system. Conclusion: This simple and cost effective production process could be recruited for large scale production of rhGH.

  5. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    Science.gov (United States)

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  6. Is human hepatocellular carcinoma a hormone-responsive tumor?

    Institute of Scientific and Technical Information of China (English)

    Massimo Di Maio; Bruno Daniele; Sandra Pignata; Ciro Gallo; Ermelinda De Maio; Alessandro Morabito; Maria Carmela Piccirillo; Francesco Perrone

    2008-01-01

    Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Sex hormones receptors are expressed in a significant proportion of HCC samples. Following preclinical and epidemiological studies supporting a relationship between sex hormones and HCC tumorigenesis, several randomized controlled trials (RCTs) tested the efficacy of the anti-estrogen tamoxifen as systemic treatment. Largest among these trials showed no survival advantage from the administration of tamoxifen, and the recent Cochrane systematic review produced a completely negative result. This questions the relevance of estrogen receptor-mediated pathways in HCC. However, a possible explanation for these disappointing results is the lack of proper patients selection according to sex hormones receptors expression, but unfortunately the interaction between this expression and efficacy of tamoxifen has not been studied adequately. It has been also proposed that negative results might be explained if tamoxifen acts in HCC via an estrogen receptor-independent pathway, that requires higher doses than those usually administered, but an Asian RCT conducted to assess dose-response effect was completely negative. Interesting, preliminaryresults have been obtained when hormonal treatment (tamoxifen or megestrol) has been selected according to the presence of wild-type or variant estrogen receptors respectively, but no large RCTs are available to support this strategy. Negative results have been obtained also with anti-androgen therapy. In conclusion, there is no robust evidence to consider HCC a hormone-responsive tumor. Hormonal treatments should not be part of the current management of HCC.

  7. Survival function Of Realization process for Hemodynamic and hormonal effects of human GH in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Geetha.T

    2014-12-01

    Full Text Available Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin or placebo and vice versa 1–2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH. The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure without a significant change in heart rate .In summary, human ghrelin elicited a potent, long lasting GH release and had beneficial hemodynamic effects via reducing cardiac after load and increasing cardiac output without an increase in heart rate. Thus, the purpose of this study was to investigate hemodynamic and hormonal effects of intravenous ghrelin in healthy volunteers. This paper discussed the constant stress level of healthy volunteers with times to damage of stress effect and recoveries

  8. Short-term effect of recombinant human growth hormone in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Becker, U; Grønbaek, M;

    1994-01-01

    As growth hormone possesses anabolic properties that are active on protein metabolism, and thus of potential benefit to patients with chronic liver disease, we determined the metabolic effects of recombinant human growth hormone on insulin-like growth factor-I (IGF-I) its specific binding proteins......, and liver function. Twenty consecutive patients with cirrhosis were randomized to recombinant human growth hormone (Norditropin, 4 I.U. twice daily) subcutaneously for 6 weeks (n = 10) or conventional medical treatment (n = 10). The serum concentrations of insulin-like growth factor-I in the recombinant...... human growth hormone group increased after 3 (p growth factor-I during the treatment period was expressed as area under the curve (AUC). The AUCIGF-I was significantly larger...

  9. Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors

    Directory of Open Access Journals (Sweden)

    Thomas L. Shaak

    2013-01-01

    Full Text Available DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine the relative androgenicity, estrogenicity, and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR, only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors and their biological effects.

  10. Physiological Study on the Relation of Heart Rate Variability in Ageing and Thyroid Hormone Disorder

    Directory of Open Access Journals (Sweden)

    Elsayed A. M. Shokr

    2016-04-01

    Full Text Available The present study aimed to investigate whether cardiac autonomic dysfunction in aging human might be related to an underlying thyroid disturbance. ageing has been associated with hypothyroidism and cardiac autonomic dysfunction. On the basis of body mass index (BMI, 150 patients were grouped into three groups (n = 50 48 years ± 2, 55 years ± 2 and 63 years ± 2. Electrocardiogram was recorded using PowerLab system and the time and frequency domain measures of heart rate variability (HRV were calculated. Fasting blood samples were drawn for measurement of serum thyroid stimulating hormone (TSH, total thyroxin (T4 and total triiodothyronine (T3 concentrations. The levels of TSH, T4 and T3 were not significantly different between the groups. The frequency domain HRV parameter reflecting parasympathetic tone (high-frequency normalized units, HFnu was significantly reduced in aging third groups group. The parameters which reflect sympathetic activation (Heart rate, low-frequency normalized units; LFnu and the LF/HF ratio were significantly increased in the aging group. HFnu was significantly and negatively correlated with age, whereas LFnu and LF/HF ratio were significantly and positively correlated with the above mentioned parameters. No significant relationships were noted between the HRV parameters and the levels of TSH or thyroid hormones. Cardiac autonomic dysfunction in aging human is not linked with underlying thyroid disturbance.

  11. Position stand on androgen and human growth hormone use.

    Science.gov (United States)

    Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

    2009-08-01

    Hoffman, JR, Kraemer, WJ, Bhasin, S, Storer, T, Ratamess, NA, Haff, GG, Willoughby, DS, and Rogol, AD. Position stand on Androgen and human growth hormone use. J Strength Cond Res 23(5): S1-S59, 2009-Perceived yet often misunderstood demands of a sport, overt benefits of anabolic drugs, and the inability to be offered any effective alternatives has fueled anabolic drug abuse despite any consequences. Motivational interactions with many situational demands including the desire for improved body image, sport performance, physical function, and body size influence and fuel such negative decisions. Positive countermeasures to deter the abuse of anabolic drugs are complex and yet unclear. Furthermore, anabolic drugs work and the optimized training and nutritional programs needed to cut into the magnitude of improvement mediated by drug abuse require more work, dedication, and preparation on the part of both athletes and coaches alike. Few shortcuts are available to the athlete who desires to train naturally. Historically, the NSCA has placed an emphasis on education to help athletes, coaches, and strength and conditioning professionals become more knowledgeable, highly skilled, and technically trained in their approach to exercise program design and implementation. Optimizing nutritional strategies are a vital interface to help cope with exercise and sport demands (). In addition, research-based supplements will also have to be acknowledged as a strategic set of tools (e.g., protein supplements before and after resistance exercise workout) that can be used in conjunction with optimized nutrition to allow more effective adaptation and recovery from exercise. Resistance exercise is the most effective anabolic form of exercise, and over the past 20 years, the research base for resistance exercise has just started to develop to a significant volume of work to help in the decision-making process in program design (). The interface with nutritional strategies has been less

  12. Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology-Like Setting.

    Directory of Open Access Journals (Sweden)

    Linda W M van Kerkhof

    Full Text Available Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time-point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. When diurnal variation is larger than the inter-individual variation, time of day should be taken into account. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food.The aim of the present study was to determine whether a set of often used biomarkers shows diurnal variation in a setting resembling large molecular epidemiology studies, i.e., non-fasted and limited control possibilities for other environmental influences.We show that markers for which diurnal variation is not an issue are adrenocorticotropic hormone, follicle stimulating hormone, estradiol and high-density lipoprotein. For all other tested markers diurnal variation was observed in at least one gender (cholesterol, cortisol, dehydroepiandrosterone sulfate, free fatty acids, low-density lipoprotein, luteinizing hormone, prolactin, progesterone, testosterone, triglycerides, total triiodothyronine and thyroid-stimulating hormone or could not reliably be detected (human growth hormone.Thus, studies investigating these markers should take diurnal variation into account, for which we provide some options. Furthermore, our study indicates the need for investigating diurnal variation (in literature or experimentally before setting up studies measuring markers in routine and controlled settings, especially since time-of-day likely matters for many more

  13. Protein Hormones and Immunity‡

    Science.gov (United States)

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  14. Thyroid hormone transporters and deiodinases in the developing human hypothalamus

    NARCIS (Netherlands)

    Friesema, E.C.; Visser, T.J.; Borgers, A.J.F.; Kalsbeek, A.; Swaab, D.F.; Fliers, E.; Alkemade, A.

    2012-01-01

    OBJECTIVE: Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monocarboxylate

  15. Thyroid hormone transporters and deiodinases in the developing human hypothalamus

    NARCIS (Netherlands)

    E.C.H. Friesema (Edith); T.J. Visser (Theo); A.J. Borgers (Anke); A. Kalsbeek (Andries); D.F. Swaab (Dick); E. Fliers (Eric); A. Alkemade (Anneke)

    2012-01-01

    textabstractObjective: Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monoc

  16. Thyroid hormone transporters and deiodinases in the developing human hypothalamus

    NARCIS (Netherlands)

    Friesema, E.C.; Visser, T.J.; Borgers, A.J.F.; Kalsbeek, A.; Swaab, D.F.; Fliers, E.; Alkemade, A.

    2012-01-01

    OBJECTIVE: Thyroid hormone (TH) signaling in brain cells is dependent on transport of TH across the plasma membrane followed by intracellular deiodination and binding to the nuclear TH receptors. The aim of this study is to investigate the expression of the specific TH transporters monocarboxylate t

  17. Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones

    NARCIS (Netherlands)

    Bao, A.-M.; Swaab, D.F.

    2007-01-01

    Previous studies have shown that the total number of corticotropin-releasing hormone (CRH)-stained neurons in the human hypothalamic paraventricular nucleus (PVN) increases with age. To determine whether this age-related change depends on gender and whether circulating sex hormones play a role, we

  18. Influence of glucocorticoids and growth hormone on insulin sensitivity in humans.

    Science.gov (United States)

    Yuen, K C J; Chong, L E; Riddle, M C

    2013-06-01

    The seminal concept proposed by Sir Harold Himsworth more than 75 years ago that a large number of patients with diabetes were 'insulin insensitive', now termed insulin resistance, has now expanded to include several endocrine syndromes, namely those of glucocorticoid excess, and growth hormone excess and deficiency. Synthetic glucocorticoids are increasingly used to treat a wide variety of chronic diseases, whereas the beneficial effects of recombinant growth hormone replacement therapy in children and adults with growth hormone deficiency have now been well-recognized for over 25 years. However, clinical and experimental studies have established that increased circulating levels of glucocorticoids and growth hormone can also lead to worsening of insulin resistance, glucose intolerance, overt diabetes mellitus and cardiovascular disease. Improved understanding of the physiological 24-h rhythmicity of glucocorticoid and growth hormone secretion and its influence on the dawn phenomenon and the Staub-Trauggot effect has therefore led to renewed interest in studies on the mechanisms of insulin resistance induced by exogenous administration of glucocorticoids and growth hormone in humans. In this review, we describe the physiological events that result from the presence of resistance to insulin action at the level of skeletal muscle, adipose tissue, and liver, describe the known mechanisms of glucocorticoid- and growth hormone-mediated insulin resistance, and provide an update of the contributions of glucocorticoids and growth hormone to understanding the pathophysiology of insulin resistance and its effects on several endocrine syndromes. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  19. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    Science.gov (United States)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  20. Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development.

    Science.gov (United States)

    Goodman, Julie E; Kerper, Laura E; Boyce, Catherine Petito; Prueitt, Robyn L; Rhomberg, Lorenz R

    2010-10-01

    Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case-control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Long-term effects of human growth hormone-releasing hormone and photoperiod on hormone release and puberty in dairy heifers.

    Science.gov (United States)

    Ringuet, H; Pelletier, G; Brazeau, P; Gaudreau, P; Guilbault, L A; Morisset, J; Couture, Y; Petitclerc, D

    1994-10-01

    Forty-eight Holstein dairy heifers (98.9 kg BW; 3 mo old) were subjected for 246 d to twice-daily s.c. injections of saline (CTL) or human growth hormone-releasing hormone (GRH; 5 micrograms/kg BW) and to photoperiods of 8 h of light (L): 16 h of dark (D) or 16L:8D according to a 2 x 2 factorial arrangement of treatments. Jugular blood samples were collected from 16 heifers at 3, 4, 8, and 11 mo of age to monitor prolactin, growth hormone, and estradiol-17 beta. Plasma progesterone concentrations were monitored weekly in all heifers as an index of puberty (> 1 ng/mL). Growth hormone release was induced by GRH (P GRH heifers. However, GRH-induced GH response was less (P GRH, photoperiod, and days of treatment on GRH-induced GH response; AUC was greater in GRH-16L:8D than in GRH-8L:16D heifers at 3 mo but less at 8 mo of age. The PRL concentrations were similar for both photoperiods at 3 mo (36.4 vs 41.7 ng/mL) and 8 mo (16.2 vs 12.8 ng/mL) of age but were greater in 16L:8D vs 8L:16D heifers at 4 mo (18.4 vs 39.3 ng/mL) and 11 mo (26.3 vs 44.1 ng/mL) of age (photoperiod x day interaction, P GRH-treated heifers (271 vs 284 kg BW; GRH x photoperiod interaction, P = .10). In conclusion, GH response is maintained throughout 8 mo of GRH treatment, and a 16L:8D photoperiod will reduce age and weight at puberty in heifers. Furthermore, refractoriness to photoperiod-induced PRL changes was detected.

  2. Short-term effect of recombinant human growth hormone in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Becker, U; Grønbaek, M;

    1994-01-01

    As growth hormone possesses anabolic properties that are active on protein metabolism, and thus of potential benefit to patients with chronic liver disease, we determined the metabolic effects of recombinant human growth hormone on insulin-like growth factor-I (IGF-I) its specific binding proteins...... an increase in very low levels of insulin-like growth factor-I, even in patients with cirrhosis with advanced disease, but the clinical benefits remain to be demonstrated....

  3. Advances on human milk hormones and protection against obesity.

    Science.gov (United States)

    Savino, F; Benetti, S; Liguori, S A; Sorrenti, M; Cordero Di Montezemolo, L

    2013-11-03

    Extensive research shows that breast milk could have positive health effects not limited to infancy, but extend into childhood and adulthood. Recently many studies have provided new evidence on the long—term positive effects of breastfeeding, in particular protection against obesity and type 2 diabetes, suggesting that breast milk may have a role in the programming of later metabolic diseases. The mechanism throughout breastfeeding that exerts these effects has been a major focus of interest for researchers and it is still not completely known. There are some hints for biological plausibility of beneficial effects of breastfeeding including macronutrient intake, hormonal and behavioural mechanisms related to breast milk composition. Breast milk biochemical components, such as protein quantity and quality, polyunsaturated fatty acids, oligosaccharides, cytokines and hormones, in particular leptin, adiponectin and resistin together with the breastfeeding practice itself can influence infants feeding behaviour and regulation of growth and appetite control later in life. Further research is needed to confirm the possibility that hormones present in breast milk exert a metabolic and beneficial effects.

  4. Human rhabdomyosarcoma cells express functional pituitary and gonadal sex hormone receptors: Therapeutic implications

    Science.gov (United States)

    PONIEWIERSKA-BARAN, AGATA; SCHNEIDER, GABRIELA; SUN, WENYUE; ABDELBASET-ISMAIL, AHMED; BARR, FREDERIC G.; RATAJCZAK, MARIUSZ Z.

    2016-01-01

    Evidence has accumulated that sex hormones play an important role in several types of cancer. Because they are also involved in skeletal muscle development and regeneration, we were therefore interested in their potential involvement in the pathogenesis of human rhabdomyosarcoma (RMS), a skeletal muscle tumor. In the present study, we employed eight RMS cell lines (three fusion positive and five fusion negative RMS cell lines) and mRNA samples obtained from RMS patients. The expression of sex hormone receptors was evaluated by RT-PCR and their functionality by chemotaxis, adhesion and direct cell proliferation assays. We report here for the first time that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptors are expressed in established human RMS cell lines as well as in primary tumor samples isolated from RMS patients. We also report that human RMS cell lines responded both to pituitary and gonadal sex hormone stimulation by enhanced proliferation, chemotaxis, cell adhesion and phosphorylation of MAPKp42/44 and AKT. In summary, our results indicate that sex hormones are involved in the pathogenesis and progression of RMS, and therefore, their therapeutic application should be avoided in patients that have been diagnosed with RMS. PMID:26983595

  5. The relationship of appetitive, reproductive and posterior pituitary hormones to alcoholism and craving in humans.

    Science.gov (United States)

    Kenna, George A; Swift, Robert M; Hillemacher, Thomas; Leggio, Lorenzo

    2012-09-01

    A significant challenge for understanding alcoholism lies in discovering why some, but not other individuals, become dependent on alcohol. Genetic, environmental, cultural, developmental, and neurobiological influences are recognized as essential factors underlying a person's risk for becoming alcohol dependent (AD); however, the neurobiological processes that trigger this vulnerability are still poorly understood. Hormones are important in the regulation of many functions and several hormones are strongly associated with alcohol use. While medical consequences are important, the primary focus of this review is on the underlying confluence of appetitive/feeding, reproductive and posterior pituitary hormones associated with distinct phases of alcoholism or assessed by alcohol craving in humans. While these hormones are of diverse origin, the involvement with alcoholism by these hormone systems is unmistakable, and demonstrates the complexity of interactions with alcohol and the difficulty of successfully pursuing effective treatments. Whether alcohol associated changes in the activity of certain hormones are the result of alcohol use or are the result of an underlying predisposition for alcoholism, or a combination of both, is currently of great scientific interest. The evidence we present in this review suggests that appetitive hormones may be markers as they appear involved in alcohol dependence and craving, that reproductive hormones provide an example of the consequences of drinking and are affected by alcohol, and that posterior pituitary hormones have potential for being targets for treatment. A better understanding of the nature of these associations may contribute to diagnosing and more comprehensively treating alcoholism. Pharmacotherapies that take advantage of our new understanding of hormones, their receptors, or their potential relationship to craving may shed light on the treatment of this disorder.

  6. BINDING OF GONADOTROPHIN-RELEASING HORMONE WITH ITS RECEPTORS ON HUMAN PLACENTAL MEMBRANES

    Institute of Scientific and Technical Information of China (English)

    QIUXiu-Di; WANGHan-Zheng; GONGYue-Ting

    1989-01-01

    Theeffects of gonadotrophin--relensing hormone (GnRH) onthe bindingof125I-labelled GnRH agonist to human placental membranes were studied. The GnRH binding sites of human plaoenta had a high specificity but low affinity. The natural GnRH had a slightly

  7. Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study

    DEFF Research Database (Denmark)

    Andersen, O; Haugaard, S B; Flyvbjerg, A

    2004-01-01

    BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than ...

  8. Translational mixed-effects PKPD modelling of recombinant human growth hormone - from hypophysectomized rat to patients

    DEFF Research Database (Denmark)

    Thorsted, A; Thygesen, P; Agersø, H;

    2016-01-01

    BACKGROUND AND PURPOSE: We aimed to develop a mechanistic mixed-effects pharmacokinetic (PK)-pharmacodynamic (PD) (PKPD) model for recombinant human growth hormone (rhGH) in hypophysectomized rats and to predict the human PKPD relationship. EXPERIMENTAL APPROACH: A non-linear mixed-effects model...

  9. Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and biogenesis in human hair follicles.

    Science.gov (United States)

    Vidali, Silvia; Knuever, Jana; Lerchner, Johannes; Giesen, Melanie; Bíró, Tamás; Klinger, Matthias; Kofler, Barbara; Funk, Wolfgang; Poeggeler, Burkhard; Paus, Ralf

    2014-01-01

    Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary-thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30 nM), TSH (10 mU ml(-1)), thyroxine (T4) (100 nM), and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable.

  10. Gastroenteric hormone responses to hedonic eating in healthy humans.

    Science.gov (United States)

    Monteleone, Palmiero; Scognamiglio, Pasquale; Monteleone, Alessio Maria; Perillo, Donato; Canestrelli, Benedetta; Maj, Mario

    2013-08-01

    Hedonic eating differentiates from homeostatic eating on two main aspects: the first one is that eating occurs when there is no need for calorie ingestion and the second one is that the food is consumed exclusively for its gustatory and rewarding properties. Gastroeneteric hormones such as ghrelin, colecystokinin-33 (CCK) and peptide YY3-36 (PYY3-36) are known to play a pivotal role in the homeostatic control of food intake. To the contrary, their role in hedonic eating has been never investigated. Here we report peripheral responses of CCK, PYY3-36 and ghrelin to the consumption of food for pleasure in well-nourished satiated healthy subjects. Plasma levels of CCK, PYY3-36 and ghrelin were measured in 7 satiated healthy subjects before and after ad libitum consumption of both a highly pleasurable food (hedonic eating) and an isoenergetic non-pleasurable food (non-hedonic eating). The consumption of food for pleasure was associated to a significantly increased production of the hunger hormone ghrelin and a significantly decreased secretion of the satiety hormone CCK. No significant changes in plasma PYY3-36 levels occurred in the two eating conditions. These preliminary data demonstrate that in hedonic eating the peripheral hunger signal represented by ghrelin secretion is enhanced while the satiety signal of CCK production is decreased. This could be responsible for the persistence of peripheral cues allowing a continued eating as well as for the activation of endogenous reward mechanisms, which can drive food consumption in spite of no energy need, only for reward. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Assessing gonadal hormone contributions to affective psychopathologies across humans and animal models.

    Science.gov (United States)

    Mueller, S C; Grissom, E M; Dohanich, G P

    2014-08-01

    Despite increasing acknowledgement of hormonal contributions to mood and anxiety disorders, the underlying mechanisms by which gonadal hormones influence psychopathology-related behaviours remain unknown. This review focuses on recent research that examines the influence of gonadal steroid hormones, including androgens, oestrogens, and progesterone, on mood and anxiety-related behaviours in human health and disease. To this aim, the literature was surveyed for studies that assess conditions with suspected underlying hormonal imbalances in otherwise healthy participants (e.g., premenstrual dysphoric disorder, postmenopausal depression) as well as conditions linked to congenital endocrine abnormalities (e.g., Turner Syndrome, Klinefelter Syndrome, polycystic ovary syndrome, congenital adrenal hyperplasia, familial male precocious puberty, androgen insensitivity syndrome). Furthermore, to better inform clinical work and to create a translational bridge, a second goal was to set human psychopathologies and animal models of these conditions side-by-side. In the second part of the review, based on consistencies revealed in the existing literature across conditions, a new model for the impact of gonadal hormones on anxious and depressed behavioural states is proposed. Finally, we conclude by proposing directions for future research, including the development of specific tasks suitable for cross-species comparisons to increase our knowledge of the role of gonadal hormones in mood and anxiety.

  12. Association of hormonal responses and performance of student pilots during acceleration training on the human centrifuge

    Science.gov (United States)

    Wirth, D.; Rohleder, N.; Welsch, H.

    2005-08-01

    Prediction of student pilots' +Gz tolerance by stress hormone levels would be a useful tool in aviation medicine. The aim of the present study was to analyze the relationship between neuroendocrine parameters with performance during acceleration training on the human centrifuge (HC).We investigated 21 student pilots during self-controlled acceleration training on the HC. Adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine were measured after individual training sessions and at rest. Performance was defined by several characteristics including maximum tolerated acceleration. ACTH and cortisol, were significantly higher 20 minutes after acceleration training compared to the resting condition. Subjects tolerated a maximal acceleration of +6.69 Gz. HPA hormone levels and responses were associated with maximum tolerated acceleration +Gz. These findings support the expectation that acceleration- induced increases in stress hormones may enable the organism to tolerate a higher acceleration and could therefore be used as predictors for acceleration tolerance.

  13. Ovine prolactin and human growth hormone derivatives. Specific modification of their alpha-amino groups.

    Science.gov (United States)

    Caridad, J J; Nowicki, C; Santomé, J A; Wolfenstein-Todel, C

    1988-06-01

    The alpha-amino group of ovine prolactin (oPRL) and human growth hormone (hGH) was selectively modified by transamination with glyoxylic acid. No difference was found in the binding capacity of transaminated oPRL to rat liver lactogenic receptors with respect to its control, although both samples showed a decrease in its binding capacity with reference to the native hormone. This decrease was due to conformational changes caused by the reaction conditions and not by the transamination itself, as shown by the circular dichroism spectra. Transaminated hGH retained the full binding capacity of the hormone. These results suggest that the alpha-amino group is not relevant for the binding to lactogenic liver receptors in both lactogenic hormones.

  14. (-) Arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β.

    Science.gov (United States)

    Ogungbe, Ifedayo Victor; Crouch, Rebecca A; Demeritte, Teresa

    2014-11-24

    Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (-) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor.

  15. (−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

    Science.gov (United States)

    2015-01-01

    Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

  16. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    Energy Technology Data Exchange (ETDEWEB)

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-02-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

  17. A statistical model of diurnal variation in human growth hormone

    Science.gov (United States)

    Klerman, Elizabeth B.; Adler, Gail K.; Jin, Moonsoo; Maliszewski, Anne M.; Brown, Emery N.

    2003-01-01

    The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

  18. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

    Science.gov (United States)

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

  19. Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1987-03-01

    A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical.

  20. The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

    Science.gov (United States)

    Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

    2014-09-01

    Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Surface plasmon resonance and electrochemical imunosensors for human growth hormone and antibodies against human growth hormone detection

    OpenAIRE

    Rukšnaitė, Justina

    2014-01-01

    Šioje daktaro disertacijoje buvo nagrinėjami paviršiaus plazmonų rezonanso (PPR) ir elektrocheminiai imuniniai jutikliai žmogaus augimo hormonui (ŽAH) ir antikūnams prieš žmogaus augimo hormoną (anti-ŽAH) nustatyti bei pritaikyti juos realių mėginių analizei. Šiame darbe buvo nagrinėjami nekryptingas ir kryptingas antikūnų imobilizavimo būdai PPR jutiklio lusto paviršiuje ir tirtas antikūno-antigeno komplekso formavimasis. Buvo nustatyta, kad tinkamiausias iš tirtų anti-ŽAH imobilizavimo P...

  2. Clastogenic effects of biosynthetic human growth hormone in Snell dwarf mice and CHO cells in vitro

    NARCIS (Netherlands)

    Buul, P.P.W. van; Buul-Offers, S. van

    1984-01-01

    Treatment of Snell dwarf mice with high concentrations of human growth hormone from pituitaries as well as of bacterial origin, significantly increased the frequencies of chromosomal aberrations in bone-marrow cells, as measured by the micronucleus test. In vitro treatment of Chinese hamster ovary

  3. Clastogenic effects of biosynthetic human growth hormone in Snell dwarf mice and CHO cells in vitro

    NARCIS (Netherlands)

    Buul, P.P.W. van; Buul-Offers, S. van

    1984-01-01

    Treatment of Snell dwarf mice with high concentrations of human growth hormone from pituitaries as well as of bacterial origin, significantly increased the frequencies of chromosomal aberrations in bone-marrow cells, as measured by the micronucleus test. In vitro treatment of Chinese hamster ovary (

  4. Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

    NARCIS (Netherlands)

    E.A. Croes (Esther); G. Roks (Gerwin); G.H. Jansen; P.C. Nijssen; C.M. van Duijn (Cock)

    2002-01-01

    textabstractA 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic

  5. PSYCHOSOCIAL EFFECTS OF 2 YEARS OF HUMAN GROWTH-HORMONE TREATMENT IN TURNER SYNDROME

    NARCIS (Netherlands)

    SLIJPER, FME; SINNEMA, G; AKKERHUIS, GW; BRUGMANBOEZEMAN, A; FEENSTRA, J; DENHARTOG, L; HEUVEL, F

    1993-01-01

    Thirty-eight girls with Turner syndrome were treated for 2 years with human growth hormone. Both parents and patients carried out assessments of the effects of treatment on various aspects of psychosocial functioning. The children used the Piers-Harris Self-Concept Scale and the Social Anxiety Scale

  6. PSYCHOSOCIAL EFFECTS OF 2 YEARS OF HUMAN GROWTH-HORMONE TREATMENT IN TURNER SYNDROME

    NARCIS (Netherlands)

    SLIJPER, FME; SINNEMA, G; AKKERHUIS, GW; BRUGMANBOEZEMAN, A; FEENSTRA, J; DENHARTOG, L; HEUVEL, F

    1993-01-01

    Thirty-eight girls with Turner syndrome were treated for 2 years with human growth hormone. Both parents and patients carried out assessments of the effects of treatment on various aspects of psychosocial functioning. The children used the Piers-Harris Self-Concept Scale and the Social Anxiety Scale

  7. Effects of growth hormone on glucose and fat metabolism in human subjects

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Møller, Louise; Krag, Morten Brøgger

    2007-01-01

    This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover...

  8. Pattern of hormone receptors and human epidermal growth factor ...

    African Journals Online (AJOL)

    2015-02-05

    Feb 5, 2015 ... Key words: Breast cancer, human epidermal growth factor receptor 2/neu, immunohistochemistry, ... therapy.[6‑8] Of all these prognostic and predictive factors, ... one of the biggest private medical laboratories in Nigeria.

  9. Translational mixed-effects PKPD modelling of recombinant human growth hormone - from hypophysectomized rat to patients

    DEFF Research Database (Denmark)

    Thorsted, Anders; Thygesen, Peter; Agersø, Henrik

    2016-01-01

    BACKGROUND AND PURPOSE: We aimed to develop a mechanistic mixed-effects pharmacokinetic (PK)-pharmacodynamic (PD) (PKPD) model for recombinant human growth hormone (rhGH) in hypophysectomized rats and to predict the human PKPD relationship. EXPERIMENTAL APPROACH: A non-linear mixed-effects model...... was developed from experimental PKPD studies of rhGH and effects of long-term treatment as measured by insulin-like growth factor 1 (IGF-1) and bodyweight gain in rats. Modelled parameter values were scaled to human values using the allometric approach with fixed exponents for PKs and unscaled for PDs...... a clinically relevant biomarker, IGF-1, to a primary clinical end-point, growth/bodyweight gain. Scaling of the model parameters provided robust predictions of the human PKPD in growth hormone-deficient patients including variability....

  10. cDNA microarray reveals signaling pathways involved in hormones expression of human pituitary.

    Science.gov (United States)

    Ma, Yue-Yun; Qi, Xiao-Fei; Song, Shao-Jun; Zhao, Zhan-Yong; Zhu, Zhi-Dong; Qi, Jia; Zhang, Xin; Xiao, Hua-Sheng; Teng, Yun; Han, Ze-Guang

    2005-09-01

    Pituitary, a master gland of neuroendocrine system, secretes hormones that orchestrate many physiological processes, under the regulation of multiple signaling pathways. To investigate the genes involved in hormones expression of human pituitary, homemade cDNA microarray containing 14,800 human genes/ESTs were used to profile the gene expression in both fetal and adult pituitaries. Seven hundred and twelve known genes changed over 2-fold between the both tissues. Of which, 23 genes were changed with hormones expression in aging were confirmed by RT-PCR, not only the known regulators such as Pit1, GATA4, ESRRA, GABA-A, and EMK, but also LOC55884, DUSP3, PNN, and RCL, which had not been reported to be involved in the hormones expression. Correspondingly, the mRNAs of GH, PRL, POMC, TSH-beta, FSH-beta, and LH-beta, was increased as much as 6- to 20-fold in adult pituitary than those in fetal pituitary, by real-time quantitative RT-PCR assay. In addition, the mRNAs of signaling pathways, such as cAMP-PKA-CREB, PI3K-Akt, and PKA-ERK were further investigated. Of them, it was only cAMP-PKA-CREB pathway, but not PI3K-Akt and PKA-ERK have the same expressing pattern as hormones. It suggested that cDNA microarray is highly advantages to profile the differential expressed genes that were involved in hormones expression of human pituitary, but it might ignore some responding proteins regulated posttranscriptionally.

  11. Gastrointestinal hormones and motility of the human sphincter of Oddi.

    Science.gov (United States)

    Ono, K; Suzuki, H; Hada, R; Sasaki, M; Endoh, M

    1985-07-01

    We investigated the mechanism of humoral control of bile discharge into the duodenum. The actions of the GB, SO and duodenum were monitered by cinecholecystocholangiogrphy combined with manometry of the SO area using a hydraulic-capillary infusion system or MIKRO-TIP, and these were correlated with the plasma concentrations of GI hormones. We concluded that one of the most significant roles of the sphincter of Oddi is to limit bile flow. This postulation was favored by the observation of so-called 'spasm' of the SO where 8 to 10 contractions per min., in contrast to 'normal' contraction of 2 to 4 per min., were seen. On this special occasion, no discharge of the contrast material into the duodenum was noticed. Exogenous or endogenous CCK causes a coordinated action of the GB contraction, the SO relaxation and relaxation of the adjacent segment of the duodenum, resulting in an effective discharge of bile into the duodenum. The effect of Pancreozymin on bile discharge revealed by endoscopic cinematography was that Pancreozymin first made the orifice of the papilla of Vater widely open with a profuse bile flow and following this, caused a repeated shuttering action of the orifice with minimal discharge of bile. This observation opposes the opinion that active SO contractile activity is necessary to bile flow into the duodenum. Caerulein or CCK-33 caused no 'post-inhibition' enhancement of the SO activity that was seen in case of Pancreozymin administration. Motilin, calcium or other substances contained in Pancreozymin (Boots) might be causative for this enhancement.

  12. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  13. Discrimination of Recombinant from Natural Human Growth Hormone Using DNA Aptamers

    OpenAIRE

    2011-01-01

    Detection of athletes who use synthetic human growth hormone (hGH; or somatotropin) to enhance physical strength and obtain an advantage in competitive sports is a formidable problem, as rhGH is virtually identical to the natural pituitary hormone. However, some post-translational and other modifications have been documented by chromatographic separation and mass spectrometry (MS) in a small percentage of rhGH. In the present work, development of DNA aptamers against research-grade rhGH and n...

  14. Pancreatic hormones are expressed on the surfaces of human and rat islet cells through exocytotic sites

    DEFF Research Database (Denmark)

    Larsson, L I; Hutton, J C; Madsen, O D

    1989-01-01

    . Electron microscopy reveals the labeling to occur at sites of exocytotic granule release, involving the surfaces of extruded granule cores. The surfaces of islet cells were labeled both by polyclonal and monoclonal antibodies, excluding that receptor-interacting, anti-idiotypic hormone antibodies were...... responsible for the staining. Human insulin cells were surface-labeled by monoclonal antibodies recognizing the mature secretory products, insulin and C-peptide but not with monoclonal antibodies specific for proinsulin. Thus, routing of unprocessed preproinsulin to the cell surface may not account...... for these results. It is concluded that the staining reflects interactions between the appropriate antibodies and exocytotic sites of hormone release....

  15. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    Science.gov (United States)

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  16. Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM).

    Science.gov (United States)

    Smyth, Hugh D C; Becket, Gordon; Mehta, Samir

    2002-05-01

    A 2 x 2 factorial design was performed to determine the effect of a permeation enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination of the two treatments on the permeation enhancement of a model peptide, LHRH (luteinizing hormone releasing hormone), through human epidermal membrane (HEM). In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and sucrose (an electroosmotic flow marker) were also investigated. Structural changes in the HEM were monitored via conductance measurements, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times passive permeability, P), was greater than during iontophoresis alone (I; 14.3) and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E, indicating the mechanisms of action of the individual enhancement strategies were likely to be located at different sites in the skin. Also, no synergistic enhancement was observed with I + E for either TEAB or sucrose. For TEAB, permeability enhancement due to I (approximately 1400) was much higher than that due to E (14.9), and no additive effect could be detected. For sucrose, E had no effect on either passive or iontophoretic permeability, eliminating the possibility that electroosmosis could explain increases in LHRH permeability. Evidence of synergy between E and I was found, with conductance measurements indicating that I + E synergistically increased the membrane permeability to conducting ions (Na+ and Cl-). It appears these pathways were not available for transport for the solutes used in the current study. DSC and IR investigations showed significant changes in stratum corneum lipid structure following E treatment but not following I. These findings probably arise from the localized action of iontophoresis compared with the bulk action of enhancer. In summary, increased LHRH delivery through HEM in

  17. The stress hormone cortisol blocks perceptual learning in humans.

    Science.gov (United States)

    Dinse, Hubert R; Kattenstroth, J C; Lenz, M; Tegenthoff, M; Wolf, O T

    2017-03-01

    Cortisol, the primary glucocorticoid (GC) in humans, influences neuronal excitability and plasticity by acting on mineralocorticoid and glucocorticoid receptors. Cellular studies demonstrated that elevated GC levels affect neuronal plasticity, for example through a reduction of hippocampal long-term potentiation (LTP). At the behavioural level, after treatment with GCs, numerous studies have reported impaired hippocampal function, such as impaired memory retrieval. In contrast, relatively little is known about the impact of GCs on cortical plasticity and perceptual learning in adult humans. Therefore, in this study, we explored the impact of elevated GC levels on human perceptual learning. To this aim, we used a training-independent learning approach, where lasting changes in human perception can be induced by applying passive repetitive sensory stimulation (rss), the timing of which was determined from cellular LTP studies. In our placebo-controlled double-blind study, we used tactile LTP-like stimulation to induce improvements in tactile acuity (spatial two-point discrimination). Our results show that a single administration of hydrocortisone (30mg) completely blocked rss-induced changes in two-point discrimination. In contrast, the placebo group showed the expected rss-induced increase in two-point discrimination of over 14%. Our data demonstrate that high GC levels inhibit rss-induced perceptual learning. We suggest that the suppression of LTP, as previously reported in cellular studies, may explain the perceptual learning impairments observed here.

  18. In vitro effects of sex hormones in human meibomian gland epithelial cells.

    Science.gov (United States)

    Schröder, Antje; Abrar, Daniel B; Hampel, Ulrike; Schicht, Martin; Paulsen, Friedrich; Garreis, Fabian

    2016-10-01

    Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (β-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -β (ERα, ERβ) and progesterone receptor (PR) in HMGEC. PR, ERα and ERβ expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERβ. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model.

  19. Degradation and Stabilization of Peptide Hormones in Human Blood Specimens.

    Directory of Open Access Journals (Sweden)

    Jizu Yi

    Full Text Available Plasma hormone peptides, including GLP-1, GIP, Glucagon, and OXM, possess multiple physiological roles and potential therapeutic and diagnostic utility as biomarkers in the research of metabolic disorders. These peptides are subject to proteolytic degradation causing preanalytical variations. Stabilization for accurate quantitation of these active peptides in ex vivo blood specimens is essential for drug and biomarker development. We investigated the protease-driven instability of these peptides in conventional serum, plasma, anticoagulated whole blood, as well as whole blood and plasma stabilized with protease inhibitors. The peptide was monitored by both time-course Matrix-Assisted Laser Desorption Ionization Time-to-Flight Mass Spectrometry (MALDI -TOF MS and Ab-based assay (ELISA or RIA. MS enabled the identification of proteolytic fragments. In non-stabilized blood samples, the results clearly indicated that dipeptidyl peptidase-IV (DPP-IV removed the N-terminal two amino acid residues from GLP-1, GIP and OXM(1-37 and not-yet identified peptidase(s cleave(s the full-length OXM(1-37 and its fragments. DPP-IV also continued to remove two additional N-terminal residues of processed OXM(3-37 to yield OXM(5-37. Importantly, both DPP-IV and other peptidase(s activities were inhibited efficiently by the protease inhibitors included in the BD P800* tube. There was preservation of GLP-1, GIP, OXM and glucagon in the P800 plasma samples with half-lives > 96, 96, 72, and 45 hours at room temperature (RT, respectively. In the BD P700* plasma samples, the stabilization of GLP-1 was also achieved with half-life > 96 hours at RT. The stabilization of these variable peptides increased their utility in drug and/or biomarker development. While stability results of GLP-1 obtained with Ab-based assay were consistent with those obtained by MS analysis, the Ab-based results of GIP, Glucagon, and OXM did not reflect the time-dependent degradations revealed by MS

  20. Central stimulation of hormone release and the proliferative response of lymphocytes in humans.

    Science.gov (United States)

    Juránková, E; Jezová, D; Vigas, M

    1995-01-01

    The central nervous system (CNS) may communicate with the immune system by direct innervation of lymphoid organs and/or by neurotransmitters and changes in neuroendocrine functioning and hormone release. The consequences of selective transient changes in circulating hormones on immune functioning in humans have not yet been studied. To address this problem, the authors evaluated the lymphoproliferative responses to optimal and suboptimal concentrations of phytohemagglutinin (PHA) and pokeweek mitogen (PWM) under selective enhancement of circulating growth hormone, prolactin, or norepinephrine. The authors failed to demonstrate any effect of elevated growth hormone levels after clonidine challenge on the lymphoproliferative response to mitogens. Similarly, the results did not show any effect of elevated prolactin concentrations induced by domperidone administration on the immune test. Exposure of volunteers to cold resulted in elevation of plasma norepinephrine levels without changes in growth hormone, epinephrine, or cortisol secretion. Cold exposure induced elevation of plasma norepinephrine and reduction of the lymphoproliferative response to the suboptimal dosage of PHA. The reduction was significant 180 and 240 min after exposure. These results are indicative of a relationship between norepinephrine and immunity.

  1. Mathematical Model for Hemodynamicand Hormonal Effects of Human Ghrelin in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Geetha.T

    2014-11-01

    Full Text Available Hemodynamicand hormonal effects of human ghrelin in healthy volunteers.To investigate hemodynamic and hormonaleffects of ghrelin, a novel growth hormone (GH-releasing peptide, we gave six healthy men an intravenousbolus of human ghrelin or placebo and vice versa1–2 wk apart in a randomized fashion. Ghrelin elicited amarked increase in circulating GH . The elevation ofGH lasted longer than 60 min after the bolus injection.Injection of ghrelin significantly decreased mean arterialpressure without a significant changein heart rate .In summary, human ghrelin elicited a potent, longlastingGH release and had beneficial hemodynamic effectsvia reducing cardiac afterload and increasing cardiac outputwithout an increase in heart rate. Thus, the purpose of thisstudy was to investigate hemodynamic and hormonaleffects of intravenous ghrelin in healthy volunteers. This paper discussed the constant stress level of healthy volunteers with times to damage of stress effect andrecoveries

  2. Effects of polybrominated diphenyl ethers on thyroid hormone, neurodevelopment and fertility in rodents and humans

    Directory of Open Access Journals (Sweden)

    Marta Czerska

    2013-08-01

    Full Text Available Polybrominated diphenyl ethers (PBDEs are used as flame retardants. Due to their widespread use in many consumer products, PBDEs can be found in food as well as in the environment. Their presence has also been found in the human serum, human adipose tissue and human breast milk. Results of experimental studies suggest that the presence of PBDE in the environment is not neutral to our health. In rats and mice exposed to PBDE disturbances in thyroid hormone homeostasis and reproductive system such as changes in reproductive organs weight and disorders in sperm motility and motion were found. In rodents, pre- and postnatal exposure to PBDE can cause neurobehavioral effects. Also in humans disturbances in thyroid hormone system, weight of reproductive organs and concentrations of sex hormones associated with PBDEs serum concentrations were found. Exposure to PBDEs during pregnancy may lead to slower mental and psychomotor development in infants. In this paper the results of previous animal a nd human studies are reviewed.

  3. Organon OD 14 (tibolone) and menopausal dynamic hormone profiles.

    Science.gov (United States)

    Abdalla, H I; Hart, D M; Lindsay, R; Beastall, G H

    1986-03-01

    Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.

  4. [Concentration of thyroid stimulating hormone and activity of N-acetyl-beta-D-hexosaminidase and its isoenzymes, in serum of patients with thyroid cancer].

    Science.gov (United States)

    Zwierz, Piotr; Szajda, Sławomir D; Snarska, Jadwiga; Supronowicz, Zbigniew B; Zawadzki, Paweł; Zwierz, Krzysztof; Kamińsk, Fabian

    2006-11-01

    Thyroid cancer consists 1% of all malignant neoplasms. It is not known interrelationship between concentration of TSH in blood serum and condition of thyroid cancer. Thyroid cancer is difficult for diagnosis and differentiation. Therefore it is necessary to search for biochemical markers helpful in diagnostics of thyroid cancer. Significant increase in activity of N-acetyl-beta-D-hexosaminidase and its isoenzymes A and B in serum of patients with neoplasms of kidney and pancreas suggest approporiateness of evaluation of HEX and its isoenzymes in diagnostics of thyroid cancer. of the study--evaluation of TSH concentration and activity of HEX and its isoenzymes A and B, in serum of patients with thyroid cancer. Blood was taken from 7 patients with thyroid cancer (6 men and 1 woman). Control consisted of 7 healthy men. In blood serum concentration of TSH was determined with immunoenzymatic method on analyzer Axsym of Abbott and expressed in microU/mL. The activity of HEX and its isoenzymes A and B was determined by method of Chatterjee et al., as modified by Zwierz et.al. Determination of HEX was performed on microplate reader ELX800 BIO-TEK. Activity of HEX, HEX A and B was expressed in pKat/mL, and specific activity in pKat/mg protein). Protein was determined by biuret method and results were expressed in mg/mL. Concentration of HEX A activity in serum of thyroid cancer patients is significantly higherin comparison to healthymen (p = 0.0191). Also specific activity of HEX A in serum of thyroid cancer patients is significantly higher in comparison to healthy men (p = 0.0393). 1. Determination of TSH concentration in serum of thyroid cancer before the operation may confirm euthyreosis. 2. Determination of HEX A activity in serum may be helpful in diagnostics of thyroid cancer.

  5. Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease.

    Science.gov (United States)

    Choi, Hoon Sung; Yoo, Won Sang

    2017-06-01

    Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole. We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups. The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness. In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

  6. Hormonal regulation of c-KIT receptor and its ligand: implications for human infertility?

    Science.gov (United States)

    Figueira, Marília I; Cardoso, Henrique J; Correia, Sara; Maia, Cláudio J; Socorro, Sílvia

    2014-09-01

    The c-KIT, a tyrosine kinase receptor, and its ligand the stem cell factor (SCF) play an important role in the production of male and female gametes. The interaction of SCF with c-KIT is required for germ cell survival and growth, and abnormalities in the activity of the SCF/c-KIT system have been associated with human infertility. Recently, it was demonstrated that gonadotropic and sex steroid hormones, among others, regulate the expression of SCF and c-KIT in testicular and ovarian cells. Therefore, the hormonal (de)regulation of SCF/c-KIT system in the testis and ovary may be a cause underpinning infertility. In the present review, we will discuss the effects of hormones modulating the expression levels of SCF and c-KIT in the human gonads. In addition, the implications of hormonal regulation of SCF/c-KIT system for germ cell development and fertility will be highlighted. Copyright © 2014. Published by Elsevier GmbH.

  7. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease.

    Science.gov (United States)

    Maia, Ana Luiza; Goemann, Iuri Martin; Meyer, Erika L Souza; Wajner, Simone Magagnin

    2011-06-01

    Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T(4)) molecule, thus producing either the active form triiodothyronine (T(3); activation) or inactive metabolites (reverse T(3); inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T(3) production contributes to a portion of plasma T(3) in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T(3) concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

  8. Growth hormone and the kidney: the use of recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal insufficiency.

    Science.gov (United States)

    Fine, R N

    1991-04-01

    Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.

  9. Pregnancy-associated plasma protein A in human ovarian follicles and its association with intrafollicular hormone levels

    DEFF Research Database (Denmark)

    Bøtkjær, Jane Alrø; Jeppesen, Janni Vikkelsø; Wissing, Marie Louise

    2015-01-01

    To evaluate follicular fluid (FF) levels of pregnancy-associated plasma protein A (PAPP-A) in relation to levels of intrafollicular hormones. Furthermore, immunostaining of human follicles of varying diameters was studied for PAPP-A, antimüllerian hormone (AMH), and aromatase, and the biological ...

  10. Comparison of the effects of human and chicken ghrelin on chicken ovarian hormone release.

    Science.gov (United States)

    Sirotkin, Alexander V; Harrath, Abdel Halim; Grossmann, Roland

    2016-11-01

    The aim of the present experiments was to examine the species-specific and cell-specific effects of ghrelin on chicken ovarian hormone release. For this purpose, we compared the effects of chicken and human ghrelin on the release of estradiol (E), testosterone (T), progesterone (P) and arginine-vasotocin (AVT) by cultured fragments of chicken ovarian follicles and on the release of T and AVT by cultured ovarian granulosa cells. In cultured chicken ovarian fragments, both human and chicken ghrelin promoted E release. T output was stimulated by chicken ghrelin but not by human ghrelin. No effect of either human or chicken ghrelin on P release was observed. Human ghrelin promoted but chicken ghrelin suppressed AVT release by chicken ovarian fragments. In cultured ovarian granulosa cells, human ghrelin inhibited while chicken ghrelin stimulated T release. Both human and chicken ghrelin suppressed AVT output by chicken granulosa cells. These data confirm the involvement of ghrelin in the control of ovarian secretory activity and demonstrate that the effect of ghrelin is species-specific. The similarity of avian ghrelin on avian ovarian granulosa cells and ovarian fragments (containing both granulosa and theca cells) suggests that ghrelin can influence chicken ovarian hormones primarily by acting on granulosa cells.

  11. Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro.

    Science.gov (United States)

    Lammel Lindemann, Jan A; Angajala, Anusha; Engler, David A; Webb, Paul; Ayers, Stephen D

    2014-05-05

    Thyroid hormone (TH) modulates serum cholesterol by acting on TH receptor β1 (TRβ1) in liver to regulate metabolic gene sets. In rodents, one important TH regulated step involves induction of Cyp7a1, an enzyme in the cytochrome P450 family, which enhances cholesterol to bile acid conversion and plays a crucial role in regulation of serum cholesterol levels. Current models suggest, however, that Cyp7a1 has lost the capacity to respond to THs in humans. We were prompted to re-examine TH effects on cholesterol metabolic genes in human liver cells by a recent study of a synthetic TH mimetic which showed that serum cholesterol reductions were accompanied by increases in a marker for bile acid synthesis in humans. Here, we show that TH effects upon cholesterol metabolic genes are almost identical in mouse liver, mouse and human liver primary cells and human hepatocyte cell lines. Moreover, Cyp7a1 is a direct TR target gene that responds to physiologic TR levels through a set of distinct response elements in its promoter. These findings suggest that THs regulate cholesterol to bile acid conversion in similar ways in humans and rodent experimental models and that manipulation of hormone signaling pathways could provide a strategy to enhance Cyp7a1 activity in human patients.

  12. Free Access to Running Wheels Abolishes Hyperphagia in Human Growth Hormone Transgenic Rats

    OpenAIRE

    KOMATSUDA, Mugiko; Yamanouchi, Keitaro; Matsuwaki, Takashi; Nishihara, Masugi

    2014-01-01

    ABSTRACT Obesity is a major health problem, and increased food intake and decreased physical activity are considered as two major factors causing obesity. Previous studies show that voluntary exercise in a running wheel decreases not only body weight but also food intake of rats. We previously produced human growth hormone transgenic (TG) rats, which are characterized by severe hyperphagia and obesity. To gain more insight into the effects on physical activity to food consumption and obesity,...

  13. An insulin-induced DNA-binding protein for the human growth hormone gene.

    OpenAIRE

    Prager, D; Gebremedhin, S; Melmed, S

    1990-01-01

    The control of gene transcription is usually mediated by transacting transcriptional factors that bind to upstream regulatory elements. As insulin regulates transcription of the growth hormone (GH) gene, we tested nuclear extracts from unstimulated and insulin-stimulated Chinese hamster ovarian (CHO) cells for binding to four human GH (hGH) gene promoter oligonucleotide fragments identified as target-binding sequences by DNAse I footprinting. Using a mobility shift assay, an insulin-induced D...

  14. Subcutaneous absorption kinetics of two highly concentrated preparations of recombinant human growth hormone

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Susgaard, Søren;

    1993-01-01

    Abstract OBJECTIVE: The relative bioavailability of two highly concentrated (12 IU/ml) formulations of biosynthetic human growth hormone (GH) administered subcutaneously was compared. DESIGN: A randomized, crossover study. Conventional GH therapy was withdrawn 72 hours before each study period. T....... CONCLUSIONS: There is no significant difference between the absorption kinetics and short-term metabolic effects of these two highly concentrated formulations of biosynthetic GH. The two formulations are bioequivalent....

  15. Specific carbon-13 labelling of leucine residues in human growth hormone

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, T.; Jensen, E.B.; Junker, F.; Dalboege, H. (Novo Nordisk A/S, Bagsvaerd (Denmark)); Abildgaard, F.; Led, J.J. (Department of Chemistry, University of Copenhagen, The H.C. Oersted Institute (Denmark))

    1992-01-01

    Biosynthetic human growth hormone specifically {sup 13}C-labelled in the carbonyl positions of all 26 leucine residues has been obtained by recombiant DNA techniques using {sup 13}C-labelled leucine and an E. coli strain that requires leucine. It is shown that, on the whole, the labelling is specific with no significant mislabelling as would have been the case had the {sup 13}C-labelled leucine been metabolized. (au).

  16. A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology.

    Science.gov (United States)

    Ezcurra, Diego; Humaidan, Peter

    2014-10-03

    Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prion proteins. The actual amount of molecular LH in hMG preparations varies considerably due to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a different role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant gonadotropins (r-hFSH and r-hLH) have become available for ART therapies. Recombinant LH contains only LH molecules. In the field of reproduction there has been controversy in recent years over whether r-hLH or hCG should be used for ART. This review examines the existing evidence for molecular and functional differences between LH and hCG and assesses the clinical implications of hCG-supplemented urinary therapy compared with recombinant therapies used for ART.

  17. The influence of sex hormones on seizures in dogs and humans.

    Science.gov (United States)

    Van Meervenne, Sofie A E; Volk, Holger A; Matiasek, Kaspar; Van Ham, Luc M L

    2014-07-01

    Epilepsy is the most common chronic neurological disorder in both humans and dogs. The effect of sex hormones on seizures is well documented in human medicine. Catamenial epilepsy is defined as an increase in frequency and severity of seizures during certain periods of the menstrual cycle. Oestradiol increases seizure activity and progesterone is believed to exhibit a protective effect. The role of androgens is controversial and there is a lack of research focusing on androgens and epilepsy. Indeed, little is known about the influence of sex hormones on epilepsy in dogs. Sterilisation is believed to improve seizure control, but no systematic research has been conducted in this field. This review provides an overview of the current literature on the influence of sex hormones on seizures in humans. The literature on idiopathic epilepsy in dogs was assessed to identify potential risk factors related to sex and sterilisation status. In general, there appears to be an over-representation of male dogs with idiopathic epilepsy but no explanation for this difference in prevalence between sexes has been reported. In addition, no reliable conclusions can be drawn on the effect of sterilisation due to the lack of focused research and robust scientific evidence.

  18. Optimizing conditions for production of high levels of soluble recombinant human growth hormone using Taguchi method.

    Science.gov (United States)

    Savari, Marzieh; Zarkesh Esfahani, Sayyed Hamid; Edalati, Masoud; Biria, Davoud

    2015-10-01

    Human growth hormone (hGH) is synthesized and stored by somatotroph cells of the anterior pituitary gland and can effect on body metabolism. This protein can be used to treat hGH deficiency, Prader-Willi syndrome and Turner syndrome. The limitations in current technology for soluble recombinant protein production, such as inclusion body formation, decrease its usage for therapeutic purposes. To achieve high levels of soluble form of recombinant human growth hormone (rhGH) we used suitable host strain, appropriate induction temperature, induction time and culture media composition. For this purpose, 32 experiments were designed using Taguchi method and the levels of produced proteins in all 32 experiments were evaluated primarily by ELISA and dot blotting and finally the purified rhGH protein products assessed by SDS-PAGE and Western blotting techniques. Our results indicate that media, bacterial strains, temperature and induction time have significant effects on the production of rhGH. The low cultivation temperature of 25°C, TB media (with 3% ethanol and 0.6M glycerol), Origami strain and a 10-h induction time increased the solubility of human growth hormone.

  19. Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones.

    Science.gov (United States)

    Berenbaum, Sheri A; Beltz, Adriene M

    2011-04-01

    A key question concerns the extent to which sexual differentiation of human behavior is influenced by sex hormones present during sensitive periods of development (organizational effects), as occurs in other mammalian species. The most important sensitive period has been considered to be prenatal, but there is increasing attention to puberty as another organizational period, with the possibility of decreasing sensitivity to sex hormones across the pubertal transition. In this paper, we review evidence that sex hormones present during the prenatal and pubertal periods produce permanent changes to behavior. There is good evidence that exposure to high levels of androgens during prenatal development results in masculinization of activity and occupational interests, sexual orientation, and some spatial abilities; prenatal androgens have a smaller effect on gender identity, and there is insufficient information about androgen effects on sex-linked behavior problems. There is little good evidence regarding long-lasting behavioral effects of pubertal hormones, but there is some suggestion that they influence gender identity and perhaps some sex-linked forms of psychopathology, and there are many opportunities to study this issue.

  20. Low-dose growth hormone and human immunodeficiency virus-associated lipodystrophy syndrome: a pilot study

    DEFF Research Database (Denmark)

    Andersen, Ove; Haugaard, Steen B; Flyvbjerg, A

    2004-01-01

    BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than......' treatment of lipodystrophic HIV-infected patients with hGH, 0.7 mg day(-1), increased total and free IGF-I twofold and appeared safe and tolerable. The potential of low-dose hGH in the treatment of HIV-lipodystrophy awaits examination by placebo-controlled, randomized trials....

  1. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

    OpenAIRE

    Loubière, L S; Vasilopoulou, E.; Bulmer, J N; Taylor, P. M.; Stieger, B.; Verrey, F.; McCabe, C. J.; Franklyn, J.A.; Kilby, M. D.; Chan, S-Y

    2010-01-01

    Thyroid hormones (TH) are important for the development of the human fetus and placenta from very early gestation. The transplacental passage of TH from mother to fetus and the supply of TH into trophoblasts require the expression of placental TH plasma membrane transporters. We describe the ontogeny of the TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 in a large series (n = 110) of normal human placentae across gestation and describe their expression changes with intrauterine ...

  2. Comparison of the Influence on the Liver Function Between Thyroid Hormone Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well-Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yeon-Hee; Lim, Seok Tae; Yun, Kuk-No; Yim, Sung Kyun; Kim, Dong Wook; Jeong, Hwan-Jeong; Sohn, Myung-Hee [Chonbuk National Univ. Medical School and Hospital, Jeonju (Korea, Republic of)

    2012-06-15

    An elevated thyroid stimulating hormone level (TSH) is essential to stimulate the uptake of radioiodine into thyroid remnants and metastases and metastases of thyroid cancer when a patient under-goes high-dose radioiodine therapy. Nowadays, recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used instead of the classic method of thyroid hormone withdrawal (THW). However, beyond the therapeutic effects, clinical differences between the two methods have not yet been clearly demonstrated. The aim of this work was to investigate the effects of the two methods, especially on liver function. We identified 143 evaluable patients who were further divided into two groups: THW and rh-TSH. We first reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. We called these liver enzyme levels 'base AST' and 'base ALT.' We also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for high-dose radioiodine therapy. We called these liver enzyme levels 'follow-up AST'and 'follow-up ALT.' We compared the changes in base and follow-up liver enzyme levels and the other chemistry profiles between the two groups. The base AST and base ALT levels of the two groups were within normal range, and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up AST and ALT levels than did the rh-TSH group. Patients in the THW group. Patients in the THW group also had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However there were no statistically significant differences in ALP, total bilirubin, and triglyceride levels between the two groups. In this retrospective analysis of liver

  3. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age

    DEFF Research Database (Denmark)

    Main, Katharina M; Mortensen, Gerda Krog; Kaleva, Marko M

    2006-01-01

    Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.......Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis....

  4. Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans.

    OpenAIRE

    Fong, Y; M. Rosenbaum; Tracey, K J; Raman, G.; Hesse, D G; Matthews, D. E.; Leibel, R. L.; Gertner, J M; Fischman, D. A.; Lowry, S F

    1989-01-01

    A potentially lethal complication of trauma, malignancy, and infection is a progressive erosion of muscle protein mass that is not readily reversed by nutritional support. Growth hormone is capable of improving total body nitrogen balance, but its role in myofibrillar protein synthesis in humans is unknown. The acute, in situ muscle protein response to an infusion of methionyl human growth hormone was investigated in the limbs of nutritionally depleted subjects during a period of intravenous ...

  5. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    Science.gov (United States)

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  6. Differential action of glycoprotein hormones: significance in cancer progression.

    Science.gov (United States)

    Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

    2014-02-01

    Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

  7. [Endocrine disruptors: hormone-active chemicals from the environment: a risk to humans?].

    Science.gov (United States)

    Klingmüller, Dietrich; Alléra, A

    2011-05-01

    Many substances from the technical and natural environment can cause damage to the endocrine system. Animal tests show that so-called endocrine disruptors (ED), such as pesticides, fungicides, plasticizers (phthalates), bisphenol A (BPA), and organotin compounds can interfere with the endocrine system. In humans, it is difficult to attribute such changes to specific ED. Nevertheless, in vitro studies with human cells and tissues clearly show that ED are able to interfere with endogenous hormones, i. e. affecting the steroid hormone metabolism and intracellular signaling. Several clinical studies show that humans are also affected, including reproductive disorders like reduction of spermatogenesis, decreased testosterone production or malformation of the genitals or induction of tumors like mammary carcinoma. Facing the body of reports documenting the effects of ED, the European Union supported--inter alia--COMPRENDO, a project addressing risk assessment of particular ED in human and wildlife species, while the FDA supports the industry's actions to stop producing BPA-containing baby bottles and infant feeding cups. Some ED show an u-shaped dose response curve and specific ED have effects at levels dramatically lower than thought relevant to traditional toxicology, a phenomenon termed "Low Dose Impact". Further research is needed to clarify whether the observed findings represent associations or causal results.

  8. A proposed unified mechanism for the reduction of human breast cancer risk by the hormones of pregnancy.

    Science.gov (United States)

    Jacobson, Herbert I; Lemanski, Nicole; Agarwal, Anu; Narendran, Amithi; Turner, Kelvin E; Bennett, James A; Andersen, Thomas T

    2010-02-01

    Parity in women is associated with reduced lifetime risk of breast cancer, and hormones of pregnancy [estrogen (E), progesterone (P), human chorionic gonadotropin (hCG)] are implicated. Parity also reduces mammary cancer risk in carcinogen-exposed rats, and administering pregnancy hormones to these animals is similarly effective. Because pregnancy hormones are also able to stimulate cancer growth, we proposed to resolve this dichotomy by determining whether administered pregnancy hormones elicit the cancer-inhibiting agent alpha-fetoprotein (AFP) from the liver, which would implicate AFP as a proximal effector of hormonal anticancer activity. Accordingly, we treated groups of nitrosomethylurea-exposed rats with saline, E(3), E(2) + P, E(3) + P, hCG, or allowed them to experience pregnancy, and then monitored mammary cancer incidence and serum levels of AFP over time. Each hormone treatment reduced mammary cancer incidence and elevated serum AFP levels. To challenge human tissues, human HepG2 liver cells in culture were treated with the same hormonal agents. Each hormone regimen increased the levels of AFP in the culture medium. Medium containing AFP elicited by hCG inhibited the E(2)-stimulated proliferation of cultured human MCF7 breast cancer cells, whereas hCG alone did not inhibit their growth. Furthermore, antibodies to AFP neutralized the growth-inhibiting effect of AFP-containing HepG2 medium. We conclude that in the treatment of carcinogen-exposed rats with the hormones of pregnancy, and by inference in women who have experienced pregnancy, that AFP is a proximal agent that inhibits mammary gland cancer.

  9. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma.

    OpenAIRE

    Frohman, L A; Downs, T. R.; Heimer, E P; Felix, A M

    1989-01-01

    The plasma enzyme responsible for primary proteolytic cleavage of growth hormone-releasing hormone (GRH) at the 2-3 amino acid bond was characterized. Native GRH[GRH(1-44)-NH2 and GRH(1-40)-OH], and COOH-terminally shortened fragments [GRH(1-32)-NH2 and GRH(1-29)-NH2] were rapidly cleaved, while GRH(2-32)-NH2 was not degraded at this site. Moreover, degradation to GRH(3-44)-NH2 was unaffected by an aminopeptidase inhibitor, indicating that this metabolite was generated from a single step clea...

  10. Hormonal and Metabolic Disorders of Human Immunodeficiency Virus Infection and Substance Abuse

    Directory of Open Access Journals (Sweden)

    Jag H. Khalsa

    2006-01-01

    Full Text Available There are an estimated 200 million users of an illicit drug in the world today. In addition, an estimated 40 million people are infected with the human immunodeficiency virus (HIV and an estimated 180 million people are infected with the hepatitis C virus (HCV. Both the use of an illicit drug and the co-occurrence of infections are associated with a multitude of medical and health consequences including hormonal and metabolic disorders. Thus, the National Institute on Drug Abuse (NIDA, a part of the National Institutes of Health (NIH hosted a workshop on hormonal and metabolic disorders of HIV among substance abusers. A number of clinicians and scientists participated and discussed a wide range of issues concerning hormones, nutrition and metabolic complications in HIV and substance abuse. Their observations and the recommendations they made for future research are presented in these proceedings. The readers are encouraged to contact the NIH staff (JK, FV for technical guidance and programmatic priorities on the subject and directly contact the individual authors for collaborations.

  11. Sex hormone influence on human infants' sound characteristics: melody in spontaneous crying.

    Science.gov (United States)

    Wermke, Kathleen; Hain, Johannes; Oehler, Klaus; Wermke, Peter; Hesse, Volker

    2014-05-01

    The specific impact of sex hormones on brain development and acoustic communication is known from animal models. Sex steroid hormones secreted during early development play an essential role in hemispheric organization and the functional lateralization of the brain, e.g. language. In animals, these hormones are well-known regulators of vocal motor behaviour. Here, the association between melody properties of infants' sounds and serum concentrations of sex steroids was investigated. Spontaneous crying was sampled in 18 healthy infants, averaging two samples taken at four and eight weeks, respectively. Blood samples were taken within a day of the crying samples. The fundamental frequency contour (melody) was analysed quantitatively and the infants' frequency modulation skills expressed by a melody complexity index (MCI). These skills provide prosodic primitives for later language. A hierarchical, multiple regression approach revealed a significant, robust relationship between the individual MCIs and the unbound, bioactive fraction of oestradiol at four weeks as well as with the four-to-eight-week difference in androstenedione. No robust relationship was found between the MCI and testosterone. Our findings suggest that oestradiol may have effects on the development and function of the auditory-vocal system in human infants that are as powerful as those in vocal-learning animals.

  12. Thyroid-stimulating immunoglobulins as measured in a reporter bioassay are not detected in patients with Hashimoto's thyroiditis and ophthalmopathy or isolated upper eyelid retraction.

    Science.gov (United States)

    Wall, Jack R; Lahooti, Hooshang; El Kochairi, Ilhem; Lytton, Simon D; Champion, Bernard

    2014-01-01

    Although ophthalmopathy is mainly associated with Graves' hyperthyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ thyroid-stimulating immunoglobulin (TSI) reporter bioassay, in patients with euthyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.

  13. The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves' disease identifies a group at markedly increased risk of ophthalmopathy.

    Science.gov (United States)

    Khoo, D H; Ho, S C; Seah, L L; Fong, K S; Tai, E S; Chee, S P; Eng, P H; Aw, S E; Fok, A C

    1999-12-01

    Among Graves' Disease (GD) patients, we have observed an unexpectedly high prevalence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) negativity in those with severe ophthalmopathy. To study the possible role of thyroid autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO), TPOAb, TgAb, thyroid-stimulating immunoglobulin (TSI), and thyrotropin-binding inhibitory immunoglobulin (TBII) levels were measured, and the presence or absence of GO was assessed by a single observer in 100 consecutive patients with newly diagnosed, untreated GD who were nonsmokers. Ophthalmopathy was present in 43 patients. TSI levels (p = 0.001), and the prevalence of TPOAb-negativity (p = 0.002) were significantly higher in patients with ophthalmopathy compared to those without. Logistic regression analysis showed that TSI levels (p = 0.005) and the absence of TPOAb (p = 0.0025) were independent predictors of GO. No correlation between TBII or TgAb and eye disease was found. The prevalence of GO increased with each quartile of TSI levels. The prevalence was 20%, 36%, 52%, and 64% in the first, second, third and fourth quartiles of TSI, respectively. The odds ratio of GO (with 95% confidence intervals) when TSI levels were above the median level (1640%) was 3.6 (1.5-8.0), when TPOAb was negative it was 5.0 (1.7-14.4), and with both risk factors it was 36.6 (4.3-313.5). The prevalence of ophthalmopathy in this last group was 92.9%. The combination of negative TPOAb and high TSI levels appears to be associated with a markedly increased risk of clinically evident ophthalmopathy.

  14. Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines.

    Science.gov (United States)

    Papageorgiou, Ioannis; Grepper, Susan; Unadkat, Jashvant D

    2013-02-01

    CYP3A activity is induced by approximately 2-fold during the third trimester of human pregnancy. Placental growth hormone (PGH), estrogens (primarily 17β-estradiol), cortisol, and progesterone have the potential to modulate CYP3A activity. Therefore, we determined whether the elevated plasma concentrations of these hormones during pregnancy induce hepatic CYP3A expression. We incubated sandwich-cultured human hepatocytes (SCHH) from premenopausal female donors (n = 2) with the physiologic (unbound, 1× total) and the 10× total third trimester hormone plasma concentrations (individually and in combination) and determined their effect on CYP3A activity and the transcripts of CYP3A4, CYP3A5, and the respective hormone receptors (growth hormone receptor, glucocorticoid receptor, and estrogen receptor alpha). Of all the hormones, cortisol was the most potent inducer of CYP3A activity and CYP3A4, CYP3A5 mRNA expression. The combination of PGH/growth hormone and cortisol induced CYP3A activity and expression significantly more than did cortisol alone. When incubated with the unbound or total plasma concentration of all the hormones, CYP3A activity in SCHH was induced to an extent comparable to that observed in vivo during the third trimester. These hormones had only a modest effect on the mRNA expression of the hormone receptors. The pattern of induction observed in SCHH was reproduced in HepaRG cells but not in HuH7/HepG2 cells. SCHH or HepaRG cells could be used to determine the mechanistic basis of CYP3A induction during pregnancy and to predict the magnitude of induction likely to be observed during the first and second trimesters, when phenotyping studies to measure in vivo CYP3A activity are logistically difficult to perform.

  15. Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

    Directory of Open Access Journals (Sweden)

    Nanthakumar eThirunarayanan

    2012-10-01

    Full Text Available Taltirelin (TAL is a thyrotropin-releasing hormone (TRH analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating CNS effects in humans compared to TRH.

  16. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

    Science.gov (United States)

    Turco, Margherita Y; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G E; Brosens, Jan J; Critchley, Hilary O; Simons, Benjamin D; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J

    2017-05-01

    In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

  17. Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats.

    Science.gov (United States)

    Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

    2013-05-01

    Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method.

  18. FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans

    DEFF Research Database (Denmark)

    Søberg, Susanna; Sandholt, Camilla Helene; Z. Jespersen, Naja

    2017-01-01

    The liking and selective ingestion of palatable foods—including sweets—is biologically controlled, and dysfunction of this regulation may promote unhealthy eating, obesity, and disease. The hepatokine fibroblast growth factor 21 (FGF21) reduces sweet consumption in rodents and primates, whereas...... knockout of Fgf21 increases sugar consumption in mice. To investigate the relevance of these findings in humans, we genotyped variants in the FGF21 locus in participants from the Danish Inter99 cohort (n = 6,514) and examined their relationship with a detailed range of food and ingestive behaviors...... elevated in fasted sweet-disliking individuals. These data suggest the liver may secrete hormones that influence eating behavior...

  19. Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids.

    Science.gov (United States)

    Rhodin, A; von Ehren, M; Skottheim, B; Grönbladh, A; Ortiz-Nieto, F; Raininko, R; Gordh, T; Nyberg, F

    2014-07-01

    During recent decades, the increasing use of opioids for chronic non-cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH-deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61-year-old man presented with severe cognitive dysfunction after long-term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone-arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resonance imaging, and the ratios of the major metabolites were calculated using proton magnetic resonance spectroscopy. Cognitive testing revealed significant improvements in visuospatial cognitive function after rhGH. The hippocampal volume remained unchanged. In the right hippocampus, the N-acetylaspartate/creatine ratio (reflecting nerve cell function) was initially low but increased significantly during rhGH treatment, as did subjective cognitive, physical and emotional functioning. This case report indicates that rhGH replacement therapy could improve cognitive behaviour and well-being, as well as hippocampal metabolism and functioning in opioid-treated patients with chronic pain. The idea that GH could affect brain function and repair disabilities induced by long-term exposure to opioid analgesia is supported.

  20. Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination.

    Science.gov (United States)

    Köhrle, Josef

    2007-06-01

    Thyroid hormone metabolism by the three deiodinase selenoproteins -- DIO1, DIO2, and DIO3 -- regulates the local availability of various iodothyronine metabolites and thus mediates their effects on gene expression, thermoregulation, energy metabolism, and many key reactions during the development and maintenance of an adult organism. Circulating serum levels of thyroid hormone and thyroid-stimulating hormone, used as a combined indicator of thyroid hormone status, reflect a composite picture of: thyroid secretion; tissue-specific production of T(3) by DIO1 and DIO2 activity, which both contribute to circulating levels of T(3); and degradation of the prohormone T4, of the thyromimetically active T(3), of the inactive rT(3), of other iodothyronines metabolites with a lower iodine content and of thyroid hormone conjugates. Degradation reactions are catalyzed by either DIO1 or DIO3. Aberrant expression of individual deiodinases in disease, single nucleotide polymorphisms in their genes, and novel regulators of DIO gene expression (such as bile acids) provide a more complex picture of the fine tuning and the adaptation of systemic and local bioavailability of thyroid hormones.

  1. FAT AND CARBOHYDRATE METABOLISM IN HUMANS-A Study of Nutritional and Hormonal Effects.

    Science.gov (United States)

    Brown, J

    1960-09-01

    As an index to the rate of fat utilization in human subjects, the recovery of all radioactive carbon dioxide in the expired air was measured for one hour following intravenous injection of palmitate-1-C(14). In the normal fasted subject, about 10 per cent of the injected dose was recovered, and the proportion was lowered to about 5 per cent by administration of glucose. With prolonged fasting, the recovery of radioactive carbon dioxide did not change, despite a rising concentration of fatty acids in the serum. This was interpreted as due to the development of a balance between increasing mobilization and oxidation and was thought to indicate increasing fatty acid oxidation. In chronic undernutrition and diabetes mellitus there was increased fatty acid oxidation due presumably to adaptation to a chronic increase in fat utilization for energy. Administration of human growth hormone did not increase fat oxidation but prevented the usual inhibition produced by glucose. This was interpreted to mean that growth hormone increases fat utilization only indirectly by inhibiting the usual preferential utilization of glucose over fat.

  2. Differential sensitivity of hormone-responsive and unresponsive human prostate cancer cells (LNCaP) to tumor necrosis factor

    NARCIS (Netherlands)

    X. Zhao (X.); G.J. van Steenbrugge (Gert Jan); F.H. Schröder (Fritz)

    1992-01-01

    textabstractTwo sublines, the hormone-sensitive LNCaP-FGC and the insensitive LNCaP-r (resistant) carcinoma cell lines, originating from the parental human prostatic carcinoma cell line LNCaP were tested for sensitivity to human tumor necrosis factor-α (TNF) using the MTT assay. Irrespective of the

  3. H9c2 cardiomyoblasts produce thyroid hormone.

    Science.gov (United States)

    Meischl, Christof; Buermans, Henk P; Hazes, Thierry; Zuidwijk, Marian J; Musters, René J P; Boer, Christa; van Lingen, Arthur; Simonides, Warner S; Blankenstein, Marinus A; Dupuy, Corrine; Paulus, Walter J; Hack, C Erik; Ris-Stalpers, Carrie; Roos, Dirk; Niessen, Hans W M

    2008-05-01

    Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125 I, we found that 125 I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125 I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.

  4. Thyroid-stimulating immunoglobulins as measured in a reporter bioassay are not detected in patients with Hashimoto’s thyroiditis and ophthalmopathy or isolated upper eyelid retraction

    Directory of Open Access Journals (Sweden)

    Wall JR

    2014-10-01

    Full Text Available Jack R Wall,1 Hooshang Lahooti,1 Ilhem El Kochairi,1 Simon D Lytton,2 Bernard Champion1 1Department of Medicine, the University of Sydney, Penrith, NSW, Australia; 2SeraDiaLogistics, Munich, Germany Abstract: Although ophthalmopathy is mainly associated with Graves’ hyperthyroidism, milder eye changes are also found in about 25% of patients with Hashimoto’s thyroiditis (HT. The recent finding of negative thyrotropin receptor (TSHR antibodies, as measured in the ­Thyretain™ thyroid-stimulating immunoglobulin (TSI reporter bioassay, in patients with euthyroid Graves’ disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves’ ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves

  5. A novel pathway regulates thyroid hormone availability in rat and human hypothalamic neurosecretory neurons.

    Directory of Open Access Journals (Sweden)

    Imre Kalló

    Full Text Available Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in their axons. Intense D3-immunoreactivity was observed in axon varicosities in the external zone of the rat median eminence and the neurohaemal zone of the human infundibulum containing axon terminals of hypophysiotropic parvocellular neurons. Immuno-electronmicroscopy localized D3 to dense-core vesicles in hypophysiotropic axon varicosities. N-STORM-superresolution-microscopy detected the active center containing C-terminus of D3 at the outer surface of these organelles. Double-labeling immunofluorescent confocal microscopy revealed that D3 is present in the majority of GnRH, CRH and GHRH axons but only in a minority of TRH axons, while absent from somatostatin-containing neurons. Bimolecular-Fluorescence-Complementation identified D3 homodimers, a prerequisite for D3 activity, in processes of GT1-7 cells. Furthermore, T3-inducible D3 catalytic activity was detected in the rat median eminence. Triple-labeling immunofluorescence and immuno-electronmicroscopy revealed the presence of MCT8 on the surface of the vast majority of all types of hypophysiotropic terminals. The presence of MCT8 was also demonstrated on the axon terminals in the neurohaemal zone of the human infundibulum. The unexpected role of hypophysiotropic axons in fine-tuned regulation of T3 availability in these cells via MCT8-mediated transport and D3-catalyzed inactivation may represent a novel regulatory core mechanism for metabolism, growth, stress and reproduction in rodents and humans.

  6. Hormonal responses to training and its tapering off in competitive swimmers: relationships with performance.

    Science.gov (United States)

    Mujika, I; Chatard, J C; Padilla, S; Guezennec, C Y; Geyssant, A

    1996-01-01

    During a winter training season, the effects of 12 weeks of intense training and 4 weeks of tapering off (taper) on plasma hormone concentrations and competition performance were investigated in a group of highly trained swimmers (n = 8). Blood samples were collected and the swimmers performed their speciality in competition at weeks 10 (mid-season), 22 (pre-taper) and 26 (post-taper). No statistically significant changes were observed in the concentrations of total testosterone (TT), non-sex hormone binding globulin-bound-testosterone (NSBT), cortisol (C), luteinising hormone, thyroid stimulating hormone, triiodothyronine, thyroxine plasma catecholamines, creatine kinase and ammonia during training and taper. Mid-season NSBT: C ratio and the amount of training were statistically related (r = 0.82, P swimmers' performance capacities throughout the training season.

  7. Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies.

    Science.gov (United States)

    Stanley, Takara L; Grinspoon, Steven K

    2015-04-01

    Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone-sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH-releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding the long-term efficacy and safety of this treatment modality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Radioimmunoassay of bovine, ovine and porcine luteinizing hormone with a monoclonal antibody and a human tracer

    Energy Technology Data Exchange (ETDEWEB)

    Fosberg, M.; Tagle, R.; Madej, A.; Molina, J.R.; Carlsson, M.-A.

    1993-01-01

    A radioimmunoassay for bovine (bLH), ovine (oLH) and porcine (pLH) luteinizing hormone was developed using a human [sup 125]ILH tracer from a commercial kit and a monoclonal antibody (518B7) specific for LH but with low species specificity. Standard curves demonstrated similar binding kinetics when bLH, oLH and pLH were incubated with tracer and antibody for 2 h at room temperature. A 30-min delay in the addition of the tracer gave sufficient sensitivity when analysing pLH. Separation of antibody-bound LH from free hormone was achieved by using second antibody-coated micro Sepharose beads. The assay was validated and the performance compared with that of an RIA currently in use for determination of bLH (coefficient of correlation: 0.99 and 0.98). Regardless of the standards used, intra-assay coefficients of variation were <10% for LH concentrations exceeding 1 [mu]g/L. The inter-assay coefficients of variation were <15%. The assay was used for clinical evaluation demonstrating the pre-ovulatory LH surge in two cyclic cows, LH pulsatility in an oophorectomized ewe and LH response to GnRH injection in a boar. (au) (7 refs.).

  9. Ten years' clinical experience with biosimilar human growth hormone: a review of efficacy data.

    Science.gov (United States)

    López-Siguero, Juan Pedro; Pfäffle, Roland; Chanson, Philippe; Szalecki, Mieczyslaw; Höbel, Nadja; Zabransky, Markus

    2017-01-01

    In 2006, the European Medicines Agency (EMA) approved Omnitrope(®) as a biosimilar recombinant human growth hormone (rhGH), on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin(®), Pfizer). Data continue to be collected on the long-term efficacy of biosimilar rhGH from several on-going postapproval studies. Particular topics of interest include efficacy in indications granted on the basis of extrapolation, and whether efficacy of growth hormone treatment is affected when patients are changed to biosimilar rhGH from other rhGH products. Data from clinical development studies and 10 years of postapproval experience affirm the clinical efficacy and effectiveness of biosimilar rhGH across all approved indications. In addition, the decade of experience with biosimilar rhGH since it was approved in Europe confirms the scientific validity of the biosimilar pathway and the approval process. Concerns about clinical effect in extrapolated indications, and also about the impact of changing from other rhGH preparations, have been alleviated. Biosimilar rhGH is an effective treatment option for children who require therapy with rhGH.

  10. On the possible role of mammary-derived growth hormone in human breast cancer.

    Science.gov (United States)

    Thijssen, Jos H H

    2009-12-01

    The incidence of breast cancer has risen worldwide, especially in countries where it used to be low, very probably as a result of economic prosperity and changes in life-style. In women, the available data have resulted in the concept of progression from normal breast development to cancer through precursor lesions sensitive to hormones and growth factors that can be produced locally in the mammary gland, acting as paracrine or autocrine stimulating agents. The local endocrine environment in the breast can be different from the situation in the circulation. In the dog, growth hormone (GH) can be produced locally in the mammary glands and its production can be stimulated by progestins. This GH probably plays a paracrine role in the progesterone-induced proliferation and differentiation of mammary epithelium. There is increasing evidence that the local mammary progestin/GH-axis is operational not only in dogs but also in human breast cancer. No data are yet available on the production of mammary-derived GH in women.

  11. Structure-activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor.

    Science.gov (United States)

    Ren, Xiao-Min; Zhang, Yin-Feng; Guo, Liang-Hong; Qin, Zhan-Fen; Lv, Qi-Yan; Zhang, Lian-Ying

    2015-02-01

    Perfluoroalkyl compounds (PFCs) have been shown to disrupt thyroid functions through thyroid hormone receptor (TR)-mediated pathways, but direct binding of PFCs with TR has not been demonstrated. We investigated the binding interactions of 16 structurally diverse PFCs with human TR, their activities on TR in cells, and the activity of perfluorooctane sulfonate (PFOS) in vivo. In fluorescence competitive binding assays, most of the 16 PFCs were found to bind to TR with relative binding potency in the range of 0.0003-0.05 compared with triiodothyronine (T3). A structure-binding relationship for PFCs was observed, where fluorinated alkyl chain length longer than ten, and an acid end group were optimal for TR binding. In thyroid hormone (TH)-responsive cell proliferation assays, PFOS, perfluorohexadecanoic acid, and perfluorooctadecanoic acid exhibited agonistic activity by promoting cell growth. Furthermore, similar to T3, PFOS exposure promoted expression of three TH upregulated genes and inhibited three TH downregulated genes in amphibians. Molecular docking analysis revealed that most of the tested PFCs efficiently fit into the T3-binding pocket in TR and formed a hydrogen bond with arginine 228 in a manner similar to T3. The combined in vitro, in vivo, and computational data strongly suggest that some PFCs disrupt the normal activity of TR pathways by directly binding to TR.

  12. Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Shui-xian SHEN; Li-hua ZHU; En-bi WANG; Zeng-can YE; Jun LIN; Li-he GUO; Fei-hong LUO; Xi-hong LIU; Xin FANG

    2004-01-01

    AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A,C182S, de1186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean±SD)values for the mutants for inhibiting 125I-hGH binding to rabbit growth hormone receptor were (65±10) ng for hGHA1, (27±5.6) ng for hGHA2, and (10±0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.

  13. Thyroid Hormone Regulation of Metabolism

    Science.gov (United States)

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

  14. Anabolic processes in human skeletal muscle: restoring the identities of growth hormone and testosterone.

    Science.gov (United States)

    West, Daniel W D; Phillips, Stuart M

    2010-10-01

    that we believe are more important for stimulating hypertrophy in human skeletal muscle. Clarifying both the role of hormones in regulating muscle mass as well as the underlying basis for adaptation of skeletal muscle to resistance exercise will hopefully enhance and support the prescription of resistance exercise as an integral component of a healthy lifestyle.

  15. Effective Cellular Uptake and Efflux of Thyroid Hormone by Human Monocarboxylate Transporter 10

    Science.gov (United States)

    Friesema, Edith C. H.; Jansen, Jurgen; Jachtenberg, Jan-willem; Visser, W. Edward; Kester, Monique H. A.; Visser, Theo J.

    2008-01-01

    Cellular entry of thyroid hormone is mediated by plasma membrane transporters, among others a T-type (aromatic) amino acid transporter. Monocarboxylate transporter 10 (MCT10) has been reported to transport aromatic amino acids but not iodothyronines. Within the MCT family, MCT10 is most homologous to MCT8, which is a very important iodothyronine transporter but does not transport amino acids. In view of this paradox, we decided to reinvestigate the possible transport of thyroid hormone by human (h) MCT10 in comparison with hMCT8. Transfection of COS1 cells with hMCT10 cDNA resulted in 1) the production of an approximately 55 kDa protein located to the plasma membrane as shown by immunoblotting and confocal microscopy, 2) a strong increase in the affinity labeling of intracellular type I deiodinase by N-bromoacetyl-[125I]T3, 3) a marked stimulation of cellular T4 and, particularly, T3 uptake, 4) a significant inhibition of T3 uptake by phenylalanine, tyrosine, and tryptophan of 12.5%, 22.2%, and 51.4%, respectively, and 5) a marked increase in the intracellular deiodination of T4 and T3 by different deiodinases. Cotransfection studies using the cytosolic thyroid hormone-binding protein μ-crystallin (CRYM) indicated that hMCT10 facilitates both cellular uptake and efflux of T4 and T3. In the absence of CRYM, hMCT10 and hMCT8 increased T3 uptake after 5 min incubation up to 4.0- and 1.9-fold, and in the presence of CRYM up to 6.9- and 5.8-fold, respectively. hMCT10 was less active toward T4 than hMCT8. These findings establish that hMCT10 is at least as active a thyroid hormone transporter as hMCT8, and that both transporters facilitate iodothyronine uptake as well as efflux. PMID:18337592

  16. Disruption of thyroid hormone (TH) levels and TH-regulated gene expression by polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and hydroxylated PCBs in e-waste recycling workers.

    Science.gov (United States)

    Zheng, Jing; He, Chun-Tao; Chen, She-Jun; Yan, Xiao; Guo, Mi-Na; Wang, Mei-Huan; Yu, Yun-Jiang; Yang, Zhong-Yi; Mai, Bi-Xian

    2017-02-25

    Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are the primary toxicants released by electronic waste (e-waste) recycling, but their adverse effects on people working in e-waste recycling or living near e-waste sites have not been studied well. In the present study, the serum concentrations of PBDEs, PCBs, and hydroxylated PCBs, the circulating levels of thyroid hormones (THs), and the mRNA levels of seven TH-regulated genes in peripheral blood leukocytes of e-waste recycling workers were analyzed. The associations of the hormone levels and gene expression with the exposure to these contaminants were examined using multiple linear regression models. There were nearly no associations of the TH levels with PCBs and hydroxylated PCBs, whereas elevated hormone (T4 and T3) levels were associated with certain lower-brominated BDEs. While not statistically significant, we did observe a negative association between highly brominated PBDE congeners and thyroid-stimulating hormone (TSH) levels in the e-waste workers. The TH-regulated gene expression was more significantly associated with the organohalogen compounds (OHCs) than the TH levels in these workers. The TH-regulated gene expression was significantly associated with certain PCB and hydroxylated PCB congeners. However, the expression of most target genes was suppressed by PBDEs (mostly highly brominated congeners). This is the first evidence of alterations in TH-regulated gene expression in humans exposed to OHCs. Our findings indicated that OHCs may interfere with TH signaling and/or exert TH-like effects, leading to alterations in related gene expression in humans. Further research is needed to investigate the mechanisms of action and associated biological consequences of the gene expression disruption by OHCs.

  17. Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Carina Lund

    2016-08-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders.

  18. Thyrotropin-releasing hormone (TRH promotes wound re-epithelialisation in frog and human skin.

    Directory of Open Access Journals (Sweden)

    Natalia T Meier

    Full Text Available There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression. Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.

  19. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  20. Optimization of a recombinant human growth hormone purification process using quality by design.

    Science.gov (United States)

    Ortiz-Enriquez, Carolina; Romero-Díaz, Alexis de Jesús; Hernández-Moreno, Ana V; Cueto-Rojas, Hugo F; Miranda-Hernández, Mariana P; López-Morales, Carlos A; Pérez, Néstor O; Salazar-Ceballos, Rodolfo; Cruz-García, Norberto; Flores-Ortiz, Luis F; Medina-Rivero, Emilio

    2016-11-16

    This work describes a strategy to optimize a downstream processing of a recombinant human growth hormone (rhGH) by incorporating a quality by design approach toward meeting higher quality specifications. The optimized process minimized the presence of impurities and degradation by-products during manufacturing by the establishment of in-process controls. Capillary zone electrophoresis, reverse phase, and size-exclusion chromatographies were used as analytical techniques to establish new critical process parameters for the solubilization, capture, and intermediate purification steps aiming to maintain rhGH quality by complying with pharmacopeial specifications. The results indicated that the implemented improvements in the process allowed the optimization of the specific recovery and purification of rhGH without compromising its quality. In addition, this optimization facilitated the stringent removal of the remaining impurities in further polishing stages, as demonstrated by the analysis of the obtained active pharmaceutical ingredient.

  1. Construction of the plasmid-free strain for human growth hormone production.

    Science.gov (United States)

    Schulga, A A; Mechev, P V; Kirpichnikov, M P; Skryabin, K G; Deyev, S M

    2016-01-01

    The E. coli strain, overproducing human growth hormone (hGH) was made by integration of the hGH gene under the control of T7 promoter into the chromosomal LacZ gene of BL21(DE3) via lambda Red recombineering. The strain gave higher productivity (50 mg·L(-1)·OD550(-1)) and better growth characteristics than the corresponding strain in which the same hGH expression cassette was placed in a plasmid. The protein produced by the plasmid-free strain was purified and characterized to be hGH. The results demonstrates that a plasmid-free recombinant strain having a single-copy gene expression cassette in the chromosome could provide better gene activity regulation, higher productivity, superior growth characteristics, as well as more stringent control of the gene sequence invariance than a plasmid-based strain.

  2. Height Outcome of Recombinant Human Growth Hormone Treatment in Achondroplasia Children: A Meta-Analysis.

    Science.gov (United States)

    Miccoli, Mario; Bertelloni, Silvano; Massart, Francesco

    2016-01-01

    Although recombinant human growth hormone (rhGH) is not approved to treat short stature of achondroplasia (ACH), some studies suggested growth improvement during short-term rhGH treatment. A meta-analysis of rhGH therapy efficacy in ACH children was performed. From 12 English-language studies, 558 (54.0% males) rhGH-treated ACH children were enrolled. Administration of rhGH (median dosage 0.21 mg/kg/ week; range 0.16-0.42 mg/kg/week) improved height (Ht) from baseline [-5.069 standard deviation score (SDS; 95% CI -5.109 to -5.029); p treatment increased Ht from -5.0 to -4.0 SDS during 5 years, but insufficient data are available on both the adult Ht and the changes of body proportions. © 2016 S. Karger AG, Basel.

  3. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P growth.

  4. Subcutaneous absorption kinetics of two highly concentrated preparations of recombinant human growth hormone

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Susgaard, Søren

    1993-01-01

    of signs of endogenous GH secretion. INTERVENTIONS: At the start of each study period, GH 3 IU/m2 was injected subcutaneously. The two formulations, PenFill and PenSet, differ in the buffers used and in the relative content of mannitol and glycine. Serum profiles of GH were monitored frequently for 24......Abstract OBJECTIVE: The relative bioavailability of two highly concentrated (12 IU/ml) formulations of biosynthetic human growth hormone (GH) administered subcutaneously was compared. DESIGN: A randomized, crossover study. Conventional GH therapy was withdrawn 72 hours before each study period...... not significantly differ from 1 (p = 0.13). Neither Cmax (p = 0.74) nor Tmax (p = 0.58) of the two formulations was significantly different. Injection of the two formulations induced similar increments in serum IFG-I (p = 0.48). Serum insulin and blood glucose concentrations were not significantly different...

  5. Exogenous recombinant human growth hormone effects during suboptimal energy and zinc intake

    Directory of Open Access Journals (Sweden)

    Duro Debora

    2005-04-01

    Full Text Available Abstract Background Energy and Zinc (Zn deficiencies have been associated with nutritional related growth retardation as well as growth hormone (GH resistance. In this study, the relationship between suboptimal energy and/or Zn intake and growth in rats and their response to immunoreactive exogenous recombinant human GH (GHi, was determined. Results Rats treated with GHi and fed ad-libitum energy and Zn (100/100 had increased IGFBP-3 (p Conclusion These results suggest that GHi enhances weight gain in rats with suboptimal energy and Zn intake but does not modify energy expenditure or physical activity index. Suboptimal Zn intake did not exacerbate the reduced growth or decrease in energy expenditure observed with energy restriction.

  6. Integration and Expression of Human Growth Hormone Gene in Caladium bicolor

    Institute of Scientific and Technical Information of China (English)

    李宝健; 王金发; 徐增富; 许友卿; 余慕贞; 何新; 沈玉

    1994-01-01

    Human growth hormone (hGH) gene has been inserted into the plasmid pLGV1103 to give the recombinant plasmid pLB-9. It has been introduced into the agrobacterium containing plasmid pGV3850. The recombinant Ti plasmid pGL198(hGH) has been obtained by homologous recombination. The monocotyledon Caladium bicolor has been transferred with pGL198 (hGH) with the leaf-disk co-cultivation method, and transgenic plants have been regenerated. The results of nopaline analysis, NPT II detection Southern blot and Western blot show that the hGH gene was integrated into the genome of Caladium bicolor, and a 22-kD protein was synthesized in the transgenic plants.

  7. Progressive pituitary hormone deficiency following radiation therapy in adults; Deficiencia progressiva dos hormonios adeno-hipofisarios apos radioterapia em adultos

    Energy Technology Data Exchange (ETDEWEB)

    Loureiro, Rafaela A.; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia]. E-mail: rafaela_loureiro@hotmail.com

    2004-10-01

    Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

  8. Discrimination of recombinant from natural human growth hormone using DNA aptamers.

    Science.gov (United States)

    Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Edge, Allison

    2011-04-01

    Detection of athletes who use synthetic human growth hormone (hGH; or somatotropin) to enhance physical strength and obtain an advantage in competitive sports is a formidable problem, as rhGH is virtually identical to the natural pituitary hormone. However, some post-translational and other modifications have been documented by chromatographic separation and mass spectrometry (MS) in a small percentage of rhGH. In the present work, development of DNA aptamers against research-grade rhGH and natural hGH with adsorption of the rhGH aptamers against natural hGH was shown to produce a small family of aptamer sequences that bound consistently with greater affinity to rhGH over a low nanogram-to-microgram range in ELISA-like microplate assays. This collection of rhGH discriminatory aptamer sequences shared some short sequence segments and secondary structural features. The top rhGH discriminatory aptamers also appeared to cross-react with human myoglobin and BSA but not with bone collagen peptides and an unrelated viral envelope peptide. The cross-reactivity results suggested several strings of up to five consecutive amino acids that might serve as common epitopes for aptamer binding. SDS-PAGE revealed that the rhGH existed largely as a 45-kDa dimer, and the natural hGH was almost exclusively monomeric. The existence of the rhGH dimer suggests that a discontinuous "bridge" epitope may exist on the rhGH, which spans the subunits, thereby accounting somewhat for the difference in detection. Overall, these results suggest that aptamers might be useful for routine, presumptive laboratory screening to identify athletes who are potentially cheating by administration of rhGH.

  9. Product wastage from modern human growth hormone administration devices: a laboratory and computer simulation analysis

    Directory of Open Access Journals (Sweden)

    Pollock RF

    2013-08-01

    Full Text Available Richard F Pollock,1 Yujun Qian,2 Tami Wisniewski,3 Lisa Seitz,4 Anne-Marie Kappelgaard2 1Ossian Health Economics and Communications GmbH, Basel, Switzerland; 2Novo Nordisk AS, Bagsværd, Denmark; 3Novo Nordisk Inc, Princeton, NJ, USA; 4Novo Nordisk Pharma GmbH, Mainz, Germany Background: Treatment of growth hormone disorders typically involves daily injections of human growth hormone (GH over many years, incurring substantial costs. We assessed the extent of undesired GH loss due to leakage in the course of pen preparation prior to injection, and differences between the prescribed dose, based on patient weight, and the actual delivered dose based on pen dosing increments in five GH administration devices. Methods: Norditropin® prefilled FlexPro®, NordiFlex®, NordiLet®, and durable NordiPen®/SimpleXx® 5 mg pens (Novo Nordisk A/S, Bagsværd, Denmark and durable Omnitrope® Pen-5 devices (Sandoz, Holzkirchen, Germany were tested (n = 40 for each device type. Product wastage was measured in accordance with validated protocols in an ISO (International Organization for Standardization 11608-1 and Good Manufacturing Practice compliant laboratory. The average mass of wasted GH from each device type was measured in simulations of dripping with the needle attached prior to injection and while setting a dose. Statistical significance (P < 0.05 was confirmed by Student's t-test, and a model was constructed to estimate mean annual GH wastage per patient in cohorts of pediatric patients with GH disorders. Results: Mean GH mass wasted with the needle on prior to injection was 0.0 µg with Norditropin pens, relative to 98 µg with Omnitrope Pen-5. During dose dialing, 0.0–2.3 µg of GH was lost with Norditropin pens versus 0.8 µg with Omnitrope Pen-5. All Norditropin and Omnitrope device comparisons were statistically significant. Modeling GH wastage in a US cohort showed 5.5 mg of annual GH wastage per patient with FlexPro versus 43.6 mg with

  10. Mineral, amino acid, and hormonal composition of chicken eggshell powder and the evaluation of its use in human nutrition

    NARCIS (Netherlands)

    Schaafsma, A; Pakan, [No Value; Hofstede, GJH; Muskiet, FAJ; Van Der Veer, E; De Vries, PJF

    2000-01-01

    Chicken eggshell powder (ESP) might be an attractive source of Ca for human nutrition. To study its nutritional value, we analyzed minerals, amino acids, and hormones in commercially available Slovakian ESP. The mineral composition was compared with three Dutch ESP samples that differed in feed and

  11. Mineral, amino acid, and hormonal composition of chicken eggshell powder and the evaluation of its use in human nutrition

    NARCIS (Netherlands)

    Schaafsma, A; Pakan, [No Value; Hofstede, GJH; Muskiet, FAJ; Van Der Veer, E; De Vries, PJF

    2000-01-01

    Chicken eggshell powder (ESP) might be an attractive source of Ca for human nutrition. To study its nutritional value, we analyzed minerals, amino acids, and hormones in commercially available Slovakian ESP. The mineral composition was compared with three Dutch ESP samples that differed in feed and

  12. Expression of thyrotropin and thyroid hormone receptors in adipose tissue of patients with morbid obesity and/or type 2 diabetes: effects of weight loss.

    Science.gov (United States)

    Nannipieri, M; Cecchetti, F; Anselmino, M; Camastra, S; Niccolini, P; Lamacchia, M; Rossi, M; Iervasi, G; Ferrannini, E

    2009-09-01

    Increased thyroid-stimulating hormone (TSH) and FT(3) levels are often found in clinically euthyroid obese individuals. Information on thyroid gene expression in human adipose tissue is scarce. The objective of this study was to measure the expression of the TSH receptor (TSHR) and the thyroid hormone receptor (TRalpha1) genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese individuals and to test the effect of weight loss on these genes. This study is a prospective study involving 107 obese (body mass index (BMI)=46+/-8 kg m(-2), 52 with type 2 diabetes or impaired glucose tolerance) and 12 lean nondiabetic participants. A total of 27 obese patients were restudied 1 year after gastric bypass surgery. Total RNA was extracted from SAT and VAT obtained at baseline from all participants, and from SAT in obese patients post surgery. Circulating TSH and FT(3) levels were 170 and 36%, respectively, higher in obese patients than in controls. In SAT, TSHR and TRalpha1 were reduced in the obese by 67 and 33%, respectively, regardless of glucose tolerance. A similar trend was found in VAT. Post surgery, a BMI decrease of 33% was associated with a decrease in TSH and FT(3) levels and with a 150 and 70% increase in SAT of TSHR and TRalpha1, respectively. In both subcutaneous and visceral fat, the thyroid gene expression (especially TSHR) is reduced in obesity. The reversal of these changes with major weight loss and the reciprocal changes in plasma TSH and FT(3) levels suggest a role for adipocytes in the regulation of TSH and thyroid hormones.

  13. INDUKSI MATURASI BELUT SAWAH (Monopterus albus DENGAN HORMON HUMAN CHORIONIC GONADOTROPIN DAN ANTIDOPAMIN

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    Wiwin Kusuma Atmaja Putra

    2013-08-01

    Full Text Available Penelitian maturasi belut sawah (Monopterus albus dengan Hormone human Chorionic Gonadotropin dan antidopamin dilakukan di Kolam Percobaan Babakan, Institut Pertanian Bogor. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh hormon hCG dan kombinasinya terhadap maturasi belut sawah. Penelitian ini dilakukan dengan metode ekperimental secara Rancangan Acak Lengkap (RAL dengan perlakuan kontrol (NaCl, hCG (dosis 20 IU/kg, antidopamin (AD (dosis 0,01 mg/kg, dan hCG+AD (dosis 20 IU+0,01 mg/kg dengan tujuh ulangan individu. Data dianalisis secara deskriptif dan ANOVA. Parameter uji pada penelitian ini di antaranya adalah konsentrasi estradiol-17β, gonado somatik index (GSI, hepatosomatik index (HSI, histologi gonad, tingkat kematangan gonad, diameter telur, tingkat kebuntingan, dan kualitas air (oksigen terlarut (DO, pH, amoniak, dan suhu. Hasil terbaik pada akhir penelitian ini adalah perlakuan hCG+AD dengan nilai konsentrasi estradiol-17β (13,63-95,49 pg/mL, GSI (1,25%, HSI (1,53%, TKG (IV, diameter telur (0,88 mm, dan tingkat kebuntingan (85,71%. Perlakuan kontrol dan antidopamin tidak berpengaruh dan hanya mampu mencapai tingkat kematangan gonad I. Hasil analisis parameter kualitas air adalah berkisar DO (5,32-5,58 mg/L, amoniak (0,558-0,978 mg/L, pH (6,06-6,36, dan suhu (27,80oC-27,94oC. Hasil ini menunjukkan bahwa hCG dapat menginduksi pematangan gonad belut sawah.

  14. The raman spectrum of biosynthetic human growth hormone. Its deconvolution, bandfitting, and interpretation

    Science.gov (United States)

    Tensmeyer, Lowell G.

    1988-05-01

    The Raman spectrum of amorphous biosynthetic human growth hormone, somatotropin, has been measured at high signal-to-noise ratios, using a CW argon ion laser and single channel detection. The rms signal-to-noise ratio varies from 1800:1 in the Amide I region near 1650 cm -1 region, to 500:1 in the disulfide stretch region near 500 cm -1. Component Raman bands have been extracted from the entire spectral envelope from 1800-400 cm -1, by an interactive process involving both partial deconvolution and band-fitting. Interconsistency of all bands has been achieved by multiple overlapping of adjacent regions that had been isolated for the band-fitting programs. The resulting areas of the Raman component bands have been interpreted to show the ratios of peptide conformations in the hormone: 64% α-helix, 24% β-sheet, 8% β-turns and 4% γ-turns. Analysis of the tyrosine region, usually described as a Fermi resonance doublet near ˜830-850 cm -1, shows four bands, at 825, 833, 853, and 859 cm -1 in this macromolecule. Integrated intensities of these bands (2:2:2:2) are interpreted to show that only half of the eight tyrosine residues function as hydrogen-bond bridges via the acceptance of protons. Both disulfide bridges fall within the frequency ranges for normal, unstressed SS bonds: The 511 and 529 cm -1 bands are indicative of the gauche-gauche-gauche and trans-gauche-gauche conformations, respectively.

  15. Preparation of soluble isotopically labeled human growth hormone produced in Escherichia coli.

    Science.gov (United States)

    Lee, Jin-Hee; Jeong, Ji-Seon; Kim, Sook-Kyung; Song, Jimyeong; Lee, Ji Youn; Baek, Soyun; Choi, Jun-Hyuk

    2016-11-01

    Isotopically labeled proteins have been used as internal standards for mass spectrometry (MS)-based absolute protein quantification. Although this approach can provide highly accurate analyses of proteins of interest within a complex mixture, one of the major limitations of this method is the difficulty in preparing uniformly labeled standards. Human growth hormone (hGH) is one of the most important hormones that circulate throughout the body, and its measurement is primarily of interest in the diagnosis and treatment of growth disorders. In order to provide a useful internal standard for MS-based hGH measurement, we describe an efficient strategy to produce a potentially valuable, stable isotope-labeled hGH with high purity and yield. The strategy involves the following steps: solubilization of hGH under labeling conditions, detection of stable isotope incorporation, large-scale purification, analysis of the labeled protein, and assessment of the labeling efficiency. We show that the yield of soluble hGH under selective isotopic labeling conditions can be greatly increased by optimizing protein expression and extraction. Our efficient method for generating isotopically labeled hGH does not influence the structural integrity of hGH. Finally, we assessed the efficiency of stable isotope labeling at the intact protein level, and the result was further verified by amino acid analysis. These results clearly indicate that our labeling approach allows an almost complete incorporation of (13)C6(15)N4-arginine into the hGH expressed in E.coli without detectable isotope scrambling.

  16. Purification of recombinant human growth hormone by isoelectric focusing in a multicompartment electrolyzer with Immobiline membranes.

    Science.gov (United States)

    Ettori, C; Righetti, P G; Chiesa, C; Frigerio, F; Galli, G; Grandi, G

    1992-09-01

    Recombinant human growth hormone (r-hGH) expressed in Escherichia coli, was 70-80% purified by a combination of ion-exchange chromatography and metal ion affinity chromatography. For the last purification step, a multicompartment electrolyzer was used, containing three compartments delimited by isoelectric membranes and two additional anodic and cathodic chambers. The central compartment was situated between two membranes having isoelectric points (pI) of 5.08 (anodic) and of 5.16 (cathodic), i.e. equidistant from the pI value of hGH (pI 5.12). r-hGH was isoelectric between these two membranes and could not leave the central chamber, while more acidic and more cathodic impurities collected in the two lateral chambers under the influence of the electric field. The r-hGH, thus purified, exhibited a single band by isoelectric focusing (IEF) in immobilized pH gradients (IPG) and gave recoveries greater than 90%. The problem of isoelectric precipitation in a practically ion-free environment was alleviated by focusing in 30% glycerol added with 1% neutral detergent (Nonidet-P40). The latter was eliminated by passage through a Q-Sepharose column after collecting the pI 5.12 band from the electrolyzer. Also the pre-hormone (pre-hGH) can be purified in a similar manner (30% glycerol, 1% Nonidet P-40) between two membranes having pIs 4.77 (anodic) and 4.87 (cathodic) (pre-hGH pI 4.82). This paper demonstrates the possibility of purifying by a focusing process also poorly soluble proteins at the pI.

  17. Application of human growth hormone to patients with polycystic ovary syndrome during in vitro fertilization

    Institute of Scientific and Technical Information of China (English)

    An Jin-xia; Liu Zhen

    2011-01-01

    Objective:To observe the effect of applying human growth hormone during in vitro fertilization to patients with polycystic ovary syndrome (PCOS)Methods:One hundred and twenty-one cycles of in vitro fertilization and embryo transfer in PCOS patients with anovulation from Dec.2008 to Nov.2010 were studied retrospectively.Of these 121 cycles,48 were with treatment of growth hormone (GH group),73 without GH treatment (control group).The dose of gonadotropin (Gn),the number of retrieved oocytes,good-quality embryo rate,implantation rate,frozen embryo rate,and pregnancy rate were compared.Results:The dosage of Gn was slightly higher in GH group than that in control group (29.18±8.33 vs.23.43±8.68 ampoullas,4U/ampoulla) and the number of retrieved oocytes in GH group were slightly less than that in control group (10.73±6.0vs.14.0±8.57),but there were no significant differences (P>0.05).The good-quality embryo rate (59.1% vs.33.3%),frozen embryo rate (87.5% vs.58.9%),pregnancy rate (56.5% vs.35.3 % ) and implantation rate (35.3 % vs.20.4 % ) in GH group were all significantly higher than those in control group (P<0.05).Conclusion:Early usage of GH in the ovarian hyperstimulation in PCOS patients could significantly improve good-quality embryo rate,implantation rate and pregnancy rate.

  18. [Recombinant human growth hormone treatment in short children with renal disease--our first experience].

    Science.gov (United States)

    Spasojević-Dimitrijeva, Brankica; Kostić, Mirjana; Peco-Antić, Amira; Kruscić, Divna; Cvetković, Mirjana; Milosevski-Lomić, Gordana; Paripović, Dusan

    2010-01-01

    Growth retardation is a hallmark of chronic illnesses such as chronic kidney disease in children, and it is associated with increased morbidity and mortality. The growth hormone (GH) resistance observed in uraemia can be overcome by supraphysiological doses of exogenous GH. We would like to present our first results of recombinant human growth hormone (rhGH) treatment, mainly in children on haemodialysis. Sixteen children, aged 4.5-17.1 years (mean age 11.25 +/- 3.57) with height below -2.0 standard deviation score (SDS) for age or height velocity below -2.0 SDS for age, were selected to receive rhGH therapy at our Nephrology and Haemodialysis Department. Most of them were on haemodialysis (14 children) with mean spent time 2.88 +/- 2.68 years (0-9 years) before the initiation of rhGH therapy. One half of patients were prepubertal (8 children) and the second half were in early puberty (testicular volume between 4 and 8 ml for boys and breast development B2 or B3 in girls). All patients received 28-30 IU/m2 rhGH per week by daily subcutaneous injection. The year before rhGH therapy served as a control period. During the first year of treatment, mean height velocity in haemodialysis patients increased from 2.25 cm/year to 6.59 cm/year (p first year of rhGH treatment (from -3.01 SDS to -2.77 SDS, p = 0.063). Neither weight nor the body mass index varied compared with the pretreatment period. Two patients developed worsened secondary hyperparathyroidism and were excluded from the study, but the relationship with rhGH remains uncertain. Mean height velocity significantly improved during rhGH therapy in haemodialysis patients. No significant side-effects were observed in children during three-year treatment with GH.

  19. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction.

    Science.gov (United States)

    Loubière, L S; Vasilopoulou, E; Bulmer, J N; Taylor, P M; Stieger, B; Verrey, F; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S-Y

    2010-04-01

    Thyroid hormones (TH) are important for the development of the human fetus and placenta from very early gestation. The transplacental passage of TH from mother to fetus and the supply of TH into trophoblasts require the expression of placental TH plasma membrane transporters. We describe the ontogeny of the TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 in a large series (n = 110) of normal human placentae across gestation and describe their expression changes with intrauterine fetal growth restriction (IUGR n = 22). Quantitative RT-PCR revealed that all the mRNAs encoding TH transporters are expressed in human placenta from 6 weeks gestation and throughout pregnancy. MCT8, MCT10, OATP1A2 and LAT1 mRNA expression increased with gestation. OATP4A1 and CD98 (LATs obligatory associated protein) mRNA expression reached a nadir in mid-gestation before increasing towards term. LAT2 mRNA expression did not alter throughout gestation. Immunohistochemistry localised MCT10 and OATP1A2 to villous cytotrophoblasts and syncytiotrophoblasts, and extravillous trophoblasts while OATP4A1 was preferentially expressed in the villous syncytiotrophoblasts. Whilst MCT8 protein expression was increased, MCT10 mRNA expression was decreased in placentae from IUGR pregnancies delivered in the early 3rd trimester compared to age matched appropriately grown for gestational age controls. No significant change was found in the mRNA expression of the other transporters with IUGR. In conclusion, several TH transporters are present in the human placenta from early 1st trimester with varying patterns of expression throughout gestation. Their coordinated effects may regulate both transplacental TH passage and TH supply to trophoblasts, which are critical for the normal development of the fetus and placenta. Increased MCT8 and decreased MCT10 expression within placentae of pregnancies complicated by IUGR may contribute to aberrant development of the fetoplacental unit.

  20. ELISA for Determination of Human Growth Hormone: Recognition of Helix 4 Epitopes

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    Moura Juliana F.

    2004-01-01

    Full Text Available Human growth hormone (hGH signal transduction initiates with a receptor dimerization in which one molecule binds to the receptor through sites 1 and 2. A sandwich enzyme-linked immunosorbent assay was developed for quantifying hGH molecules that present helix 4 from binding site 1. For this, horse anti-rhGH antibodies were eluted by an immunoaffinity column constituted by sepharose-rhGH. These antibodies were purified through a second column with synthetic peptide correspondent to hGH helix 4, immobilized to sepharose, and used as capture antibodies. Those that did not recognize synthetic peptide were used as a marker antibody. The working range was of 1.95 to 31.25 ng/mL of hGH. The intra-assay coefficient of variation (CV was between 4.53% and 6.33%, while the interassay CV was between 6.00% and 8.27%. The recovery range was between 96.0% to 103.8%. There was no cross-reactivity with human prolactin. These features show that our assay is an efficient method for the determination of hGH.

  1. High level expression of bioactive recombinant human growth hormone in the milk of a cloned transgenic cow.

    Science.gov (United States)

    Salamone, Daniel; Barañao, Lino; Santos, Claudio; Bussmann, Leonardo; Artuso, Jorge; Werning, Carlos; Prync, Aida; Carbonetto, Cesar; Dabsys, Susana; Munar, Carlos; Salaberry, Roberto; Berra, Guillermo; Berra, Ignacio; Fernández, Nahuel; Papouchado, Mariana; Foti, Marcelo; Judewicz, Norberto; Mujica, Ignacio; Muñoz, Luciana; Alvarez, Silvina Fenández; González, Eliseo; Zimmermann, Juan; Criscuolo, Marcelo; Melo, Carlos

    2006-07-13

    Transgenic farm animals have been proposed as an alternative to current bioreactors for large scale production of biopharmaceuticals. However, the efficiency of both methods in the production of the same protein has not yet been established. Here we report the production of recombinant human growth hormone (hGH) in the milk of a cloned transgenic cow at levels of up to 5 g l(-1). The hormone is identical to that currently produced by expression in E. coli. In addition, the hematological and somatometric parameters of the cloned transgenic cow are within the normal range for the breed and it is fertile and capable of producing normal offspring. These results demonstrate that transgenic cattle can be used as a cost-effective alternative for the production of this hormone.

  2. Testicular function in boys previously treated with recombinant-human growth hormone for non-growth hormone-deficient short stature.

    Science.gov (United States)

    Radicioni, A F; Paris, E; De Marco, E; Anzuini, A; Gandini, L; Lenzi, A

    2007-12-01

    Data on the effects of recombinant human GH (hGH) therapy during male puberty on future testis function are still inconclusive. The aim of this study was to investigate the long-term effects of recombinant hGH treatment on reproductive function in non-GH-deficient short stature boys. Eight boys with non-GH-deficient short stature, affected by constitutional delay of puberty or idiopathic short stature, were retrospectively studied after recombinant-hGH treatment to verify gonadal development, hormone production and semen quality. Auxological data, endocrinological/ andrological parameters and laboratory evaluation (GH, IGF-I, FSH, LH, testosterone, inhibin B) were assessed before treatment; after completion of pubertal development, the same parameters plus SHBG levels were evaluated and a seminal fluid examination was conducted (ejaculate volume, pH, sperm concentration, total sperm count, forward and total motility, morphology). All patients showed normal testicular volume at the final pubertal stage, with regular androgenization. Hormonal levels were within the normal adult range in all boys. Considering the immature reproductive system of these patients in comparison with adults, semen parameters (sperm count, motility, and morphology) were within almost normal limits, except in one patient. Although patients showed the wide fluctuation of semen values frequently observed at the end of puberty, the hypophysis-gonadal axis hormones were in the normal range in all adolescents. Pathological measurements of some seminal parameters were found in one patient only. This study suggests that recombinant hGH treatment has no detrimental effects on the development and maturation of male gonadal function in non- GH deficient short stature young patients.

  3. Follicle-stimulating hormone potentiates the steroidogenic activity of chorionic gonadotropin and the anti-apoptotic activity of luteinizing hormone in human granulosa-lutein cells in vitro.

    Science.gov (United States)

    Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Nicoli, Alessia; Tagliavini, Simonetta; Trenti, Tommaso; La Sala, Giovanni Battista; Simoni, Manuela

    2016-02-15

    Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy, respectively. Since these molecules act on the same receptor (LHCGR), they were traditionally assumed as equivalent in assisted reproduction techniques (ART), although differences between LH and hCG were demonstrated at molecular and physiological level. In this study, we demonstrated for the first time that co-treatment with a follicle-stimulating hormone (FSH) dose in the ART therapeutic range potentiates different LH- and hCG-dependent responses in vitro, measured in terms of cAMP, phospho-CREB, -ERK1/2 and -AKT activation, gene expression, progesterone and estradiol production in human granulosa-lutein cells (hGLC). We show that in the presence of FSH, hCG biopotency is about 5-fold increased, in the presence of FSH, in terms of cAMP activation. Accordingly, CREB phosphorylation and steroid production is increased under hCG and FSH co-treatment. LH effects, evaluated as steroidogenic cAMP/PKA pathway activation, do not change in the presence of FSH, which, however, increases LH-dependent ERK1/2 and AKT, but not CREB phosphorylation, resulting in anti-apoptotic effects. The different modulatory activity of FSH on LH and hCG action in vitro corresponds to their different physiological functions, reflecting proliferative effects exerted by LH during the follicular phase and before trophoblast development, and the high steroidogenic potential of hCG requested to sustain pregnancy from the luteal phase onwards.

  4. Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dao-Ming Liang; Jia-Yong Chen; Yi Zhang; Ping Gan; Jie Lin; An-Bao Chen

    2006-01-01

    AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo.METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model wasestablished successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method.RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%,58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P <0.05), whereas there were no significant differences (P >0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group.CONCLUSION: rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

  5. The effect of calcium phosphate nanoparticles on hormone production and apoptosis in human granulosa cells

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    Gao Li

    2010-04-01

    Full Text Available Abstract Objectives Although many nanomaterials are being used in academia, industry and daily life, there is little understanding about the effects of nanoparticles on the reproductive health of vertebral animals, including human beings. An experimental study was therefore performed here to explore the effect of calcium phosphate nanoparticles on both steroid hormone production and apoptosis in human ovarian granulosa cells. Methods Calcium phosphate nanoparticles uptaking was evaluated by transmission electron microscopy (TEM. The cell cycle was assessed with propidium iodide-stained cells (distribution of cells in G0/G1, S, and G2/M phases by flow cytometry. The pattern of cell death (necrosis and apoptosis was analyzed by flow cytometry with annexin V-FITC/PI staining. The expression of mRNAs encoding P450scc, P450arom and StAR were determined by RT-PCR. Progesterone and estradiol levels were measured by radioimmunoassay. Results TEM results confirmed that calcium phosphate nanoparticles could enter into granulosa cells, and distributed in the membranate compartments, including lysosome and mitochondria and intracellular vesicles. The increased percentage of cells in S phase when cultured with nanoparticles indicated that there was an arrest at the checkpoint from phase S-to-G2/M (from 6.28 +/- 1.55% to 11.18 +/- 1.73%, p Conclusion Calcium phosphate nanoparticles interfered with cell cycle of cultured human ovarian granulosa cells thus increasing cell apoptosis. This pilot study suggested that effects of nanoparticles on ovarian function should be extensively investigated.

  6. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Ewa Cristine Siljevik Ellis

    2006-01-01

    AIM: It is known that thyroid hormones alter the bile acid metabolism in humans, however the effect on individual enzymes has been difficult to elucidate.This is mainly due to the lack of human liver cell lines producing bile acids. We used cultures of primary human hepatocytes to study the effects of triiodothyronine (T3) on bile acid synthesis.METHODS: Primary hepatocytes were isolated from liver tissue obtained from three different patients undergoing liver resection due to underlying malignancy. The hepatocytes were cultured under serum-free conditions and treated from d 1 to d 5 with culture containing 0.1-1000 nmol/L of T3. Bile acid formation and mRNA levels of key enzymes were analysed.RESULTS: The lowest concentration of T3 decreased cholic acid (CA) formation to 43%-53% of controls and chenodeoxycholic acid (CDCA) to 52%-75% of controls on d 5. The highest dose further decreased CA formation to 16%-48% of controls while CDCA formation remained at 50%-117% of controls. Expression of mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) dose-dependently decreased.Sterol 27-hydroxylase (CYP27A1) levels also decreased,but not to the same extent.CONCLUSION: T3 dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1. CA formation is inhibited to a higher degree than CDCA, resulting in a marked decrease in the CA/CDCA ratio.

  7. Comparative Analysis of Human Growth Hormone in Serum Using SPRi, Nano-SPRi and ELISA Assays.

    Science.gov (United States)

    Vance, Stephen; Zeidan, Effat; Henrich, Vincent C; Sandros, Marinella G

    2016-01-07

    Sensitive and selective methods for the detection of human growth hormone (hGH) over a wide range of concentrations (high levels of 50-100 ng ml(-) (1) and minimum levels of 0.03 ng ml(-) (1)) in circulating blood are essential as variable levels may indicate altered physiology. For example, growth disorders occurring in childhood can be diagnosed by measuring levels of hGH in blood. Also, the misuse of recombinant hGH in sports not only poses an ethical issue it also presents serious health threats to the abuser. One popular strategy for measuring hGH misuse, relies on the detection of the ratio of 22 kDa hGH to total hGH, as non-22 kDa endogenous levels drop after exogenous recombinant hGH (rhGH) administration. Surface plasmon resonance imaging (SPRi) is an analytical tool that allows direct (label-free) monitoring and visualization of biomolecular interactions by recording changes of the refractive index adjacent to the sensor surface in real time. In contrast, the most frequently used colorimetric method, enzyme-linked immunosorbent assay (ELISA) uses enzyme labeled detection antibodies to indirectly measure analyte concentration after the addition of a substrate that induces a color change. To increase detection sensitivity, amplified SPRi uses a sandwich assay format and near infrared quantum dots (QDs) to increase signal strength. After direct SPRi detection of recombinant rhGH in spiked human serum, the SPRi signal is amplified by the sequential injection of detection antibody coated with near-infrared QDs (Nano-SPRi). In this study, the diagnostic potential of direct and amplified SPRi was assessed for measuring rhGH spiked in human serum and compared directly with the capabilities of a commercially available ELISA kit.

  8. Pituitary gland and sella turcica in human trisomy 18 fetuses.

    Science.gov (United States)

    Kjaer, I; Keeling, J W; Reintoft, I; Hjalgrim, H; Nolting, D; Fischer Hansen, B

    1998-02-26

    The purpose of this study was to elucidate the phenotypic conditions in the sella turcica/pituitary gland complex in human trisomy 18 fetuses. Fourteen human fetuses with gestational ages from 12 to 39 weeks were included in the study. Normal fetuses at corresponding ages were used as controls. Whole body and special radiographic examination was undertaken before the midsagittal cranial base block, including the pituitary gland, was excised and analyzed histologically and immunohistochemically (keratin wide spectrum [KWS], thyroid-stimulating hormone [TSH], and neurophysin [Nph]). In all trisomy 18 fetuses, TSH-positive adenopituitary tissue was present in the sella and in greater or lesser amounts pharyngeally. The neurohypophysis was Nph-positive and located normally in the sella turcica. The adenohypophyseal tissue reacted either KWS-faint or KWS-negative, whereas KWS-positive reaction occurs in normal fetuses. This circumstance might suggest an altered cytoskeletal structure of the surface ectoderm in the pituitary placode in trisomy 18. The sella turcica was malformed in all the fetuses. Very broad craniopharyngeal canals were observed in some of the fetuses. Because endocrine disorders occur in many congenital malformations, it is essential in future studies to chart the sella turcica/pituitary gland region systematically in different genotypes.

  9. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  10. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH Peptide

    Directory of Open Access Journals (Sweden)

    Pooria Mansoori

    2011-07-01

    Full Text Available Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

  11. Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS.

    Science.gov (United States)

    Knoop, Andre; Thomas, Andreas; Fichant, Eric; Delahaut, Philippe; Schänzer, Wilhelm; Thevis, Mario

    2016-05-01

    The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). The aim of the present study was to develop a method for the simultaneous detection of four different GHRHs and respective metabolites from human plasma by means of immunoaffinity purification and subsequent nano-ultrahigh performance liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The target analytes included Geref (Sermorelin), CJC-1293, CJC-1295, and Egrifta (Tesamorelin) as well as two metabolites of Geref and CJC-1293, which were captured from plasma samples using a polyclonal GHRH antibody in concert with protein A/G monolithic MSIA™ D.A.R.T.'S® (Disposable Automation Research Tips) prior to separation and detection. The method was fully validated and found to be fit for purpose considering the parameters specificity, linearity, recovery (19-37%), lower limit of detection (sports drug testing samples. Further studies are however required and warranted to account for potential species-related differences in metabolism and elimination of the target analytes.

  12. 2,4,6-Tribromophenol Interferes with the Thyroid Hormone System by Regulating Thyroid Hormones and the Responsible Genes in Mice.

    Science.gov (United States)

    Lee, Dongoh; Ahn, Changhwan; Hong, Eui-Ju; An, Beum-Soo; Hyun, Sang-Hwan; Choi, Kyung-Chul; Jeung, Eui-Bae

    2016-07-12

    2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems.

  13. Mammary tumors and serum hormones in the bitch treated with medroxyprogesterone acetate or progesterone for four years

    Energy Technology Data Exchange (ETDEWEB)

    Frank, D.W.; Kirton, K.T.; Murchison, T.E.; Quinlan, W.J.; Coleman, M.E.; Gilbertson, T.J.; Feenstra, E.S.; Kimball, F.A.

    1978-01-01

    After four years of a long term contraceptive steroid safety study, the incidence and the histologic type of mammary dysplasia produced is similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17..beta..-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose related manner in both treatment groups. Triiodothyronine, cortisol, and estradiol-17..beta.. (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary--gonadal hormone interaction in the pathogenesis of mammary neoplasia of the dog is discussed. Prolonged treatment of the beagle with massive doses of progesterone or medroxyprogesterone results in a dose related incidence of mammary modules.

  14. The Relationship of Appetitive, Reproductive and Posterior Pituitary Hormones to Alcoholism and Craving in Humans

    OpenAIRE

    2012-01-01

    A significant challenge for understanding alcoholism lies in discovering why some, but not other individuals, become dependent on alcohol. Genetic, environmental, cultural, developmental, and neurobiological influences are recognized as essential factors underlying a person's risk for becoming alcohol dependent (AD); however, the neurobiological processes that trigger this vulnerability are still poorly understood. Hormones are important in the regulation of many functions and several hormone...

  15. Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization

    NARCIS (Netherlands)

    P.J.D. Delhanty (Patric); A. Kerkwijk (Anke); M. Huisman (Martijn); B. van de Zande (Bedette); M. Verhoef-Post (Miriam); C. Gauna (Carlotta); L.J. Hofland (Leo); A.P.N. Themmen (Axel); A-J. van der Lely (Aart-Jan)

    2010-01-01

    textabstractThe composition of the plasma membrane affects the responsiveness of cells to metabolically important hormones such as insulin and vasoactive intestinal peptide. Ghrelin is a metabolically regulated hormone that activates the G protein-coupled receptor GH secretagogue receptor type 1a (G

  16. Hormonal regulation of lipoprotein lipase in adipose tissue (studies in the rat and in humans)

    NARCIS (Netherlands)

    M.G.A. Baggen (Marinus)

    1988-01-01

    textabstractCurrent data strongly suggest the most important role for insulin in the hormonal regulation of adipose tissue LPL activity. It is not clear from the literature what the role is of glucocorticoids in the regulation of the enzyme. Stress hormones as ACTH and adrenalin for example seem to

  17. Hormonal regulation of lipoprotein lipase in adipose tissue (studies in the rat and in humans)

    NARCIS (Netherlands)

    M.G.A. Baggen (Marinus)

    1988-01-01

    textabstractCurrent data strongly suggest the most important role for insulin in the hormonal regulation of adipose tissue LPL activity. It is not clear from the literature what the role is of glucocorticoids in the regulation of the enzyme. Stress hormones as ACTH and adrenalin for example seem to

  18. Screening of pharmaceuticals and hormones at the regional scale, in surface and groundwaters intended to human consumption

    Energy Technology Data Exchange (ETDEWEB)

    Vulliet, Emmanuelle, E-mail: e.vulliet@sca.cnrs.fr [Institut des Sciences Analytiques - UMR5280, Departement Service Central d' Analyse, Echangeur de Solaize, Chemin du Canal, F-69360 Solaize (France); Cren-Olive, Cecile [Institut des Sciences Analytiques - UMR5280, Departement Service Central d' Analyse, Echangeur de Solaize, Chemin du Canal, F-69360 Solaize (France)

    2011-10-15

    As part of a regional screening to evaluate the risk, for the health of populations, to certain classes of emerging substances, several families of pharmaceuticals and hormones were looked for in waters intended to drinking. Thus, 52 substances were investigated in 71 surface waters and 70 groundwaters. Results indicate that no water was free of pollutants, regardless of its origin (surface or groundwater) and the season of collect. The pharmaceuticals most frequently detected and with the highest concentration levels were salicylic acid, carbamazepine and acetaminophen. Among hormones, testosterone, androstenedione and progesterone were detected in almost all the samples. Globally the groundwaters were less contaminated than surface waters in regards pharmaceuticals frequencies and levels. On the other side, androgens and progestagens were present with comparable frequencies and levels in both compartments. The risk linked to the presence of these substances on human health is discussed. - Highlights: > Traces of 52 substances investigated in 71 surface waters and 70 groundwaters. > No water was free of pollutants, whatever its origin and the season of collect. > Globally groundwaters were less contaminated than surface waters in regards pharmaceuticals. > Hormones were present with comparable frequencies and levels in two compartments. - 52 pharmaceuticals and hormones investigated in 71 surface waters and 70 groundwaters intended to human consumption.

  19. Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

    1989-05-01

    Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and thus releasing free fatty acids, but also by increasing intrahepatic ketogenesis. Thyroid hormone availability was associated with lipolysis and ketogenesis. Ketone body concentrations after an overnight fast were only modestly elevated in hyperthyroidism resulting from increased peripheral ketone body clearance. There was a significant correlation between serum triiodothyronine levels and the ketone body metabolic clearance rate. Thus, ketone body homeostasis in human subjects resulted from the interaction of hormones such as insulin, catecholamines, and thyroid hormones regulating lipolysis, intrahepatic ketogenesis, and peripheral ketone body utilization. 58 references.

  20. Body segments and growth hormone.

    OpenAIRE

    Bundak, R; Hindmarsh, P C; Brook, C. G.

    1988-01-01

    The effects of human growth hormone treatment for five years on sitting height and subischial leg length of 35 prepubertal children with isolated growth hormone deficiency were investigated. Body segments reacted equally to treatment with human growth hormone; this is important when comparing the effect of growth hormone on the growth of children with skeletal dysplasias or after spinal irradiation.

  1. Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane

    Science.gov (United States)

    Kim, Eung-Sam; Jang, Do Soo; Yang, Seung Yun; Lee, Mi Nam; Jin, Kyeong Sik; Cha, Hyung Jin; Kim, Jin Kon; Sung, Young Chul; Choi, Kwan Yong

    2013-05-01

    Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and

  2. The impact of growth hormone on proteomic profiles: a review of mouse and adult human studies.

    Science.gov (United States)

    Duran-Ortiz, Silvana; Brittain, Alison L; Kopchick, John J

    2017-01-01

    Growth hormone (GH) is a protein that is known to stimulate postnatal growth, counter regulate insulin's action and induce expression of insulin-like growth factor-1. GH exerts anabolic or catabolic effects depending upon on the targeted tissue. For instance, GH increases skeletal muscle and decreases adipose tissue mass. Our laboratory has spent the past two decades studying these effects, including the effects of GH excess and depletion, on the proteome of several mouse and human tissues. This review first discusses proteomic techniques that are commonly used for these types of studies. We then examine the proteomic differences found in mice with excess circulating GH (bGH mice) or mice with disruption of the GH receptor gene (GHR(-/-)). We also describe the effects of increased and decreased GH action on the proteome of adult patients with either acromegaly, GH deficiency or patients after short-term GH treatment. Finally, we explain how these proteomic studies resulted in the discovery of potential biomarkers for GH action, particularly those related with the effects of GH on aging, glucose metabolism and body composition.

  3. In Vivo Bioassay of Recombinant Human Growth Hormone Synthesized in B. mori Pupae

    Directory of Open Access Journals (Sweden)

    Hanglian Lan

    2010-01-01

    Full Text Available The human growth hormone (hGH has been expressed in prokaryotic expression system with low bioactivity previously. Then the effective B. mori baculovirus system was employed to express hGH identical to mature hGH successfully in larvae, but the expression level was still limited. In this work, the hGH was expressed in B. mori pupae by baculovirus system. Quantification of recombinant hGH protein (BmrhGH showed that the expression of BmrhGH reached the level of approximately 890 μg/mL pupae supernatant solution, which was five times more than the level using larvae. Furthermore, Animals were gavaged with BmrhGH at the dose of 4.5 mg/rat.day, and the body weight gain (BWG of treated group had a significant difference (P<.01 compared with the control group. The other two parameters of liver weight and epiphyseal width were also found to be different between the two groups (P<.05. The results suggested that BmrhGH might be used as a protein drug by oral administration.

  4. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    Science.gov (United States)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  5. Stimulation tests of human growth hormone secretion by insulin, lysine vasopressin, pyrogen and glucagon

    Directory of Open Access Journals (Sweden)

    Ogawa,Norio

    1974-06-01

    Full Text Available Firstly, comparisons have been made of the secretion of human growth hormone (HGH that was induced by insulin, lysine vasopressin and pyrogen injections in order to study whether these substances can be utilized as a rapid test of HGH secretion. In insulin test, a fall of the fasting blood glucose level by 28.6% or more seemed to be sufficient to provoke adequate HGH elevation, and 9.4 ng/ml or higher HGH increment was recognized as being normal, because lysine vasopressin and pyrogen produce varying degrees of side-effects and are less specific and unpredictable in the release of HGH. Secondly, the pharmacologic effects and mechanism of action of exogenous glucagon upon the HGH secretion were studied. In normal subjects after one mg sc glucagon, there was a mean peak blood glucose level of 142. 4±3.l mg/lOO ml at 30 min, HGH levels reached a mean peak level of 22. 6±4. 8 ng/ml at 150 min, and no false negative response was noted. In patients with hypopituitarism, there was no positive response in plasma HGH levels after the sc glucagon. The present study revealed that the rise and subsequent fall of blood glucose are not the sole mechanism responsible for the effct of glucagon on HGH secretion, and that the HGH secretion in response to the sc glucagon was not triggered by cathecholamine via the stimulation of the adrenal medulla.

  6. Complete solubilization and purification of recombinant human growth hormone produced in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Min-Ji Kim

    Full Text Available High-level expression of recombinant human growth hormone (hGH in Escherichia coli (E. coli leads to the formation of insoluble aggregates as inclusion bodies devoid of biological activity. Until recently, significant efforts have been made to improve the recovery of active hGH from inclusion bodies. Here, we developed an efficient procedure for the production of completely soluble hGH by minimizing the formation of inclusion bodies and optimizing protein purification conditions. Under the newly established conditions we were able to obtain most of the total hGH in the soluble fraction. We show that the soluble protein can be efficiently purified in high yield by a series of chromatographic procedures. We analyzed the resulting hGH using various analytical techniques such as reversed-phase high-performance liquid chromatography (RP-HPLC, size-exclusion chromatography (SEC, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF mass spectrometry, and circular dichroism (CD. These multiple analyses support the conclusion that we obtained highly pure hGH with the expected molecular mass and intact secondary structure. The biological activity of purified hGH was also confirmed by evaluating its growth-promoting effect using a cell proliferation assay. Taken together, we describe a straightforward strategy for the production of completely soluble and biologically active hGH in E. coli.

  7. Twin arginine translocation system in secretory expression of recombinant human growth hormone

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Bagherinejad

    2016-01-01

    Full Text Available Recombinant protein production in E. coli has several advantages over other expression systems. Misfolding, inclusion body formation, and lack of eukaryotic post translational modification are the most disadvantages of this system. Exporting of correctly folded proteins to the outside of reductive cytoplasmic environment through twin-arginine system could help to pass these limiting steps. Two signal sequences, TorA and SufI are used at N-terminal of human growth hormone (hGH bearing DsbA gene sequence at C-terminal to enhance folding. The synthetic cassettes including the signal sequence, hGH and DsbA were transformed into E. coli BL21 (DE3 to study the effect of signal sequence and DsbA chaperone on translocation and folding of the protein. The results confirmed using signal sequence at N-terminal of targeted protein and coexpression with DsbA could transport proteins to the periplasmic space and culture media compared to control groups. Although there is no protein band of somatropin in SDS-Page of culture media samples when using SufI as signaling sequence, the study demonstrated TorA signal sequence could transport the target protein to the culture media. However, there was a considerable amount of hGH in periplasmic space when using SufI compared to control.

  8. In vivo bioassay of recombinant human growth hormone synthesized in B. mori pupae.

    Science.gov (United States)

    Lan, Hanglian; Nie, Zuoming; Liu, Yue; Lv, Zhengbing; Liu, Yingshuo; Quan, Yanping; Chen, Jianqing; Zhen, Qingliang; Chen, Qin; Wang, Dan; Sheng, Qing; Yu, Wei; Chen, Jian; Wu, Xiangfu; Zhang, Yaozhou

    2010-01-01

    The human growth hormone (hGH) has been expressed in prokaryotic expression system with low bioactivity previously. Then the effective B. mori baculovirus system was employed to express hGH identical to mature hGH successfully in larvae, but the expression level was still limited. In this work, the hGH was expressed in B. mori pupae by baculovirus system. Quantification of recombinant hGH protein (BmrhGH) showed that the expression of BmrhGH reached the level of approximately 890 microg/mL pupae supernatant solution, which was five times more than the level using larvae. Furthermore, Animals were gavaged with BmrhGH at the dose of 4.5 mg/rat.day, and the body weight gain (BWG) of treated group had a significant difference (P < .01) compared with the control group. The other two parameters of liver weight and epiphyseal width were also found to be different between the two groups (P < .05). The results suggested that BmrhGH might be used as a protein drug by oral administration.

  9. Rational Design of Potent Antagonists to the Human Growth Hormone Receptor

    Science.gov (United States)

    Fuh, Germaine; Cunningham, Brian C.; Fukunaga, Rikiro; Nagata, Shigekazu; Goeddel, David V.; Wells, James A.

    1992-06-01

    A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially-a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.

  10. Modeling of protein-anion exchange resin interaction for the human growth hormone charge variants.

    Science.gov (United States)

    Lapelosa, Mauro; Patapoff, Thomas W; Zarraga, Isidro E

    2015-12-01

    Modeling ion exchange chromatography (IEC) behavior has generated significant interest because of the wide use of IEC as an analytical technique as well as a preparative protein purification process; indeed there is a need for better understanding of what drives the unique behavior of protein charge variants. We hypothesize that a complex protein molecule, which contains both hydrophobic and charged moieties, would interact strongly with an in silico designed resin through charged electrostatic patches on the surface of the protein. In the present work, variants of recombinant human growth hormone that mimic naturally-occurring deamidation products were produced and characterized in silico. The study included these four variants: rhGH, N149D, N152D, and N149D/N152D. Poisson-Boltzmann calculations were used to determine surface electrostatic potential. Metropolis Monte Carlo simulations were carried out with the resulting variants to simulate IEC systems, examining the free energy of the interaction of the protein with an in silico anion exchange column represented by polylysine polypeptide. The results show that the charge variants have different average binding energies and the free energy of interaction can be used to predict the retention time for the different variants.

  11. Structural study of human growth hormone-releasing factor fragment (1?29) by vibrational spectroscopy

    Science.gov (United States)

    Carmona, P.; Molina, M.; Lasagabaster, A.

    1995-05-01

    The conformational structure of fragment 1-29 of human growth hormone releasing factor, hGHRF (1-29), in aqueous solution and in the solid state is investigated by infrared and Raman spectroscopy. The polypeptide backbone is found to be unordered in the solid state. However, the spectra of the peptide prepared as 5% (w/w) aqueous solutions show that approximately 28% of the peptide is involved in intermolecular β-sheet aggregation. The remainder of the peptide exists largely as disordered and β-sheet conformations with a small portion of α-helices. Tyrosine residues are found to be exposed to the solvent. The secondary structures are quantitatively examined through infrared spectroscopy, the conformational percentages being near those obtained by HONDAet al. [ Biopolymers31, 869 (1991)] using circular dichroism. The fast hydrogen/deuterium exchange in peptide groups and the absence of any NMR sign indicative of ordered structure [ G. M. CLOREet al., J. Molec. Biol.191, 553 (1986)] support that the solution conformations of the non-aggregated peptide interconvert in dynamic equilibrium. Some physiological advantages that may derive from this conformational flexibility are also discussed

  12. [Establishment of HEK293 cell lines stably expressing human parathyroid hormone receptors].

    Science.gov (United States)

    Meng, Yue; Xie, Miaomiao; Lin, Zhen; Yuan, Liang; Li, Wei; Hao, Song; Yang, Dehong

    2013-07-01

    To establish HEK293 cell lines with stable expression of human parathyroid hormone (PTH) receptors. The purified gene fragments of PTH-related peptide receptor (PTHR) and its mutant form (DSEL) were cloned separately into pcDNA3.1(+) vector after digestion with EcoR I and Not I, and the resulted pcDNA3.1(+)-PTHR and pcDNA3.1(+)-DSEL plasmids were verified by restriction enzyme digestion and DNA sequencing. HEK293 cells were transfected with these plasmids and the expression of PTHR and DSEL in the cells were examined by RT-PCR and ELSIA. Sequencing and restriction enzyme digestion analysis showed that PTHR and DSEL cDNAs were correctly cloned into pcDNA3.1(+)vector. After a 48-h transfection of HEK293 cells with the recombinant plasmids and G418 selection, the positive cell clones stably expressing the constructs were obtained, which showed expressions of PTHR and DSEL mRNAs detected by RT-PCR. These positive cells showed high levels of PLC and aAMP production in response to PTH stimulation. The HEK293 cell lines with stable expression of PTH1R or DSEL gene established in this study provide useful cell models for studying the physiological functions of PTH peptides.

  13. Effects of recombinant human growth hormone on remnant liver after hepatectomy in hepatocellular carcinoma with cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Shi-Min Luo; Li-Jian Liang; Jia-Ming Lai

    2004-01-01

    AIM: To explore the effects of recombinant human growth hormone (rhGH) on the remnant liver after hepatectomy in hepatocellular carcinoma with liver cirrhosis.METHODS: Twenty-four patients with hepatocellular carcinoma who underwent hepatectomy were randomly divided into 2groups: parenteral nutrition (PN) group (n=12) and rhGH+PN group (n=12). Liver function, blood glucose, AFP, serum prealbumin and transferrin were detected before operation,at post-operative d 1 and d 6. Albumin (ALB) mRNA in liver biopsy specimens was detected by RT-PCR at post-operative d 6. Liver Ki67 immunohistochemical staining was studied.RESULTS: On post-operative d 6, compared with PN group,the levels of blood glucose, serum prealbumin, transferrin,the expression of hepatic ALB mRNA and liver Ki67 labeling index were higher in rhGH+PN group.CONCLUSION: rhGH can improve protein synthesis and liver regeneration after hepatectomy in hepatocellular carcinoma with liver cirrhosis.

  14. Thiol-disulfide exchange in peptides derived from human growth hormone.

    Science.gov (United States)

    Chandrasekhar, Saradha; Epling, Daniel E; Sophocleous, Andreas M; Topp, Elizabeth M

    2014-04-01

    Disulfide bonds stabilize proteins by cross-linking distant regions into a compact three-dimensional structure. They can also participate in hydrolytic and oxidative pathways to form nonnative disulfide bonds and other reactive species. Such covalent modifications can contribute to protein aggregation. Here, we present experimental data for the mechanism of thiol-disulfide exchange in tryptic peptides derived from human growth hormone in aqueous solution. Reaction kinetics was monitored to investigate the effect of pH (6.0-10.0), temperature (4-50°C), oxidation suppressants [ethylenediaminetetraacetic acid (EDTA) and N2 sparging], and peptide secondary structure (amide cyclized vs. open form). The concentrations of free thiol containing peptides, scrambled disulfides, and native disulfide-linked peptides generated via thiol-disulfide exchange and oxidation reactions were determined using reverse-phase HPLC and liquid chromatography-mass spectrometry. Concentration versus time data were fitted to a mathematical model using nonlinear least squares regression analysis. At all pH values, the model was able to fit the data with R(2) ≥ 0.95. Excluding oxidation suppressants (EDTA and N2 sparging) resulted in an increase in the formation of scrambled disulfides via oxidative pathways but did not influence the intrinsic rate of thiol-disulfide exchange. In addition, peptide secondary structure was found to influence the rate of thiol-disulfide exchange.

  15. Associations between Maternal Body Composition and Appetite Hormones and Macronutrients in Human Milk

    Directory of Open Access Journals (Sweden)

    Sambavi Kugananthan

    2017-03-01

    Full Text Available Human milk (HM appetite hormones and macronutrients may mediate satiety in breastfed infants. This study investigated associations between maternal adiposity and concentrations of HM leptin, adiponectin, protein and lactose, and whether these concentrations and the relationship between body mass index and percentage fat mass (%FM in a breastfeeding population change over the first year of lactation. Lactating women (n = 59 provided milk samples (n = 283 at the 2nd, 5th, 9th and/or 12th month of lactation. Concentrations of leptin, adiponectin, total protein and lactose were measured. Maternal %FM was measured using bioimpedance spectroscopy. Higher maternal %FM was associated with higher leptin concentrations in both whole (0.006 ± 0.002 ng/mL, p = 0.008 and skim HM (0.005 ± 0.002 ng/mL, p = 0.007, and protein (0.16 ± 0.07 g/L, p = 0.028 concentrations. Adiponectin and lactose concentrations were not associated with %FM (0.01 ± 0.06 ng/mL, p = 0.81; 0.08 ± 0.11 g/L, p = 0.48, respectively. Whole milk concentrations of adiponectin and leptin did not differ significantly over the first year of lactation. These findings suggest that the level of maternal adiposity during lactation may influence the early appetite programming of breastfed infants by modulating concentrations of HM components.

  16. Zinc, copper, manganese, and selenium metabolism in patients with human growth hormone deficiency or acromegaly.

    Science.gov (United States)

    Aihara, K; Nishi, Y; Hatano, S; Kihara, M; Ohta, M; Sakoda, K; Uozumi, T; Usui, T

    1985-08-01

    This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.

  17. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

    Science.gov (United States)

    Johnson, Matthew W; MacLean, Katherine A; Caspers, Michael J; Prisinzano, Thomas E; Griffiths, Roland R

    2016-04-01

    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

  18. Associations between Maternal Body Composition and Appetite Hormones and Macronutrients in Human Milk

    Science.gov (United States)

    Kugananthan, Sambavi; Gridneva, Zoya; Lai, Ching T.; Hepworth, Anna R.; Mark, Peter J.; Kakulas, Foteini; Geddes, Donna T.

    2017-01-01

    Human milk (HM) appetite hormones and macronutrients may mediate satiety in breastfed infants. This study investigated associations between maternal adiposity and concentrations of HM leptin, adiponectin, protein and lactose, and whether these concentrations and the relationship between body mass index and percentage fat mass (%FM) in a breastfeeding population change over the first year of lactation. Lactating women (n = 59) provided milk samples (n = 283) at the 2nd, 5th, 9th and/or 12th month of lactation. Concentrations of leptin, adiponectin, total protein and lactose were measured. Maternal %FM was measured using bioimpedance spectroscopy. Higher maternal %FM was associated with higher leptin concentrations in both whole (0.006 ± 0.002 ng/mL, p = 0.008) and skim HM (0.005 ± 0.002 ng/mL, p = 0.007), and protein (0.16 ± 0.07 g/L, p = 0.028) concentrations. Adiponectin and lactose concentrations were not associated with %FM (0.01 ± 0.06 ng/mL, p = 0.81; 0.08 ± 0.11 g/L, p = 0.48, respectively). Whole milk concentrations of adiponectin and leptin did not differ significantly over the first year of lactation. These findings suggest that the level of maternal adiposity during lactation may influence the early appetite programming of breastfed infants by modulating concentrations of HM components. PMID:28282925

  19. Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

    Science.gov (United States)

    Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

    2016-11-01

    This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  20. Circulating microRNA as a biomarker of human growth hormone administration to patients.

    Science.gov (United States)

    Kelly, Brian N; Haverstick, Doris M; Lee, Jae K; Thorner, Michael O; Vance, Mary Lee; Xin, Wenjun; Bruns, David E

    2014-03-01

    Circulating microRNAs (miRNAs) in plasma are being studied for use as biomarkers of specific diseases and as markers of administration of pharmaceutical agents. Administration of recombinant human growth hormone (rhGH) is prohibited by sporting authorities, but it continues to be used by athletes attempting to gain an unfair advantage in athletic competition. Current methods for detection of rhGH use rely on immunoassay technology and are limited by a short time-frame in which detection of rhGH is possible. We hypothesized that administration of rhGH would alter expression of circulating miRNAs and that any changes could be detected. To identify potential miRNA targets, we utilized miRNA microarrays for screening. Confirmatory testing used real-time reverse-transcriptase (RT) quantitative PCR (qPCR) assays of selected miRNAs in 35 plasma samples obtained from (1) individuals with no known pituitary disorders, (2) patients with excess GH production, and (3) patients receiving therapeutic replacement doses of rhGH. We identified and confirmed four miRNAs that were differentially expressed in all individuals using therapeutic replacement doses of rhGH when compared to individuals with naturally high levels of GH and normal controls. This study further develops the hypothesis that circulating miRNAs may be used as biomarkers for detection of doping in sports.

  1. Hormonal regulation of dipeptidyl-aminopeptidase I activity in cultured human fibroblasts.

    Science.gov (United States)

    Davis, M H

    1987-05-01

    Human male fibroblasts, cell line GM2987, were grown in 10% Nu-Serum or fetal bovine serum. Dipeptidyl-aminopeptidase I (DAP-I) activity was higher in cells grown with Nu-Serum and cells grown in 10% fetal bovine serum purchased from Grand Island Biological Company (GIBCO) and lower in cells grown in 10% fetal bovine serum obtained from Sterile Systems, Inc. (Hyclone). The addition of 0.3 microM cortisol to all three types of sera resulted in cells that had similar levels of DAP-I activity (maximum of 800-900 nmol of beta-naphthylamine released from glycyl-L-phenylanine-beta-naphthylamine per hour per milligram of cellular protein). The addition of cortisol to Hyclone fetal bovine serum increased the DAP-I levels by up to threefold with a half-maximal response occurring at 30 nM cortisol. Triiodothyronine also could increase DAP-I levels, but only between 1.5- and 2.0-fold. Testosterone propionate increased DAP-I levels by 1.4-fold. These changes in growth media and hormones had little effect on other lysosomal enzymes or the growth characteristics of the cells.

  2. Characterization of growth hormone and prolactin produced by human pituitary in culture.

    Science.gov (United States)

    Skyler, J S; Rogol, A D; Lovenberg, W; Knazek, R A

    1977-02-01

    Fragments of a pituitary tumor from a patient with acromegaly were grown in tissue culture. The tumor secreted both growth hormone and prolactin,which were recovered in high concentrations. The nonpurified hormones were characterized and compared to their respective counterparts obtained by extraction from normal pituitaries obtained at autopsy. The tissue culture and pituitary extracted hormones were eluted from Sephadex G-100 with the same partition coefficients. Growth hormone from both sources showed parallel dose-response displacement curves, by logit-log transformation, in both specific immunoassay and in a specific lymphocyte binding assay. Prolactin from both sources was compared in specific immunoassay using three different antisera. Parallel logit-log displacement curves were seen with one antiserum, while the other two antisera yielded non-parallel curves, indicating structural differences between prolactin from the two sources. Quantitative polyacrylamide gel electrophoresis was performed using multiphasic buffer systems previously developed for characterization of each hormone. By the criteria of joint 95% confidence envelopes of retardation co-efficient and relative free mobility, tissue culture growth hormone and prolactin were indistinguishable from their pituitary-extracted counterparts. This study demonstrates that, prior to purification, tissue culture derived hormone can be characterized by multiple criteria and compared to a standard preparation. Structural differences can be detected, as in the case of prolactin. When the hormones are indistinguishable, as in the case of growth hormone, it becomes worthwhile to increase the scale of tissue cultured production, with the prospect that tissue culture may serve as a source of hormone for both experimental and therapeutic use.

  3. Mass spectrometric analysis of innovator, counterfeit, and follow-on recombinant human growth hormone.

    Science.gov (United States)

    Jiang, Haitao; Wu, Shiaw-Lin; Karger, Barry L; Hancock, William S

    2009-01-01

    We have performed a detailed characterization of recombinant human growth hormone that included the identification of the entire sequence with disulfide linkages as well as subtle modifications by a sensitive liquid chromatography coupled online with tandem mass spectrometry (LC-MS) approach using the accurate peptide mass (FTICR MS) and sequence assignment (MS/MS measurement). The extent of oxidation, deamidation, and chain cleavages were measured by the ratio of peak areas of the nonmodified peptide vs. the sum of peak area of the nonmodified and modified peptides in the same LC-MS analysis. The subtle but distinct differences were found in the recombinant human growth from the three manufacturers (the follow-on, counterfeit, and the original innovator products). In relative comparison, the follow-on product had the highest degree of oxidation at methionine residues, followed by the counterfeit product, and the original innovator product had the least amount of oxidation at all three sites with the similar oxidation order. In cases, the oxidation order was Met14 > Met125 > Met170. In contrast, the follow-on had the least amount of deamidation at aspargine (Asn149), and the counterfeit had the highest degree of deamidation at this site. For the chain cleavage, the follow-on product had the highest cleavage occurring at T 10 peptide (between Asn99 and Ser100), the counterfeit had the highest cleavage on T4 peptide, (between Glu30 and Phe31), and the original innovator product with the least amount of cleavages on both sites. These subtle but distinct differences are likely because of nonidentical manufacturing, formulation procedures, and storage conditions.

  4. MicroRNA expression and regulation in human ovarian carcinoma cells by luteinizing hormone.

    Directory of Open Access Journals (Sweden)

    Juan Cui

    Full Text Available BACKGROUND: MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH contributions to LH receptor (LHR-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR. METHODS: Human ovarian cancer cells (SKOV3 were chosen as negative control (LHR- and stably transfected to express functional LHR (LHR+, followed by incubation with LH (0-20 h. At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™, which profiled ∼ 100,000 transcripts with ∼ 400 non-coding microRNAs. FINDINGS: In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs. CONCLUSION: The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles.

  5. Activated effects of parathyroid hormone-related protein on human hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Fen-Fen Liang

    Full Text Available BACKGROUND & AIMS: After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1, which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC and LX-2 cell lines. METHODS: TGF-β1, alpha-smooth muscle actin (α-SMA, matrix metalloproteinase 2 (MMP-2, and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR after HSCs or LX-2 cells were treated with PTHrP(1-36 or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA of HSC cell culture media. RESULTS: In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs. CONCLUSIONS: PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.

  6. Activated effects of parathyroid hormone-related protein on human hepatic stellate cells.

    Science.gov (United States)

    Liang, Fen-Fen; Liu, Cui-Ping; Li, Li-Xuan; Xue, Min-Min; Xie, Fang; Guo, Yu; Bai, Lan

    2013-01-01

    After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP) has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1), which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC) and LX-2 cell lines. TGF-β1, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR) after HSCs or LX-2 cells were treated with PTHrP(1-36) or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA) of HSC cell culture media. In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs. PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.

  7. Specifying the neurobiological basis of human attachment: brain, hormones, and behavior in synchronous and intrusive mothers.

    Science.gov (United States)

    Atzil, Shir; Hendler, Talma; Feldman, Ruth

    2011-12-01

    The mother-infant bond provides the foundation for the infant's future mental health and adaptation and depends on the provision of species-typical maternal behaviors that are supported by neuroendocrine and motivation-affective neural systems. Animal research has demonstrated that natural variations in patterns of maternal care chart discrete profiles of maternal brain-behavior relationships that uniquely shape the infant's lifetime capacities for stress regulation and social affiliation. Such patterns of maternal care are mediated by the neuropeptide Oxytocin and by stress- and reward-related neural systems. Human studies have similarly shown that maternal synchrony--the coordination of maternal behavior with infant signals--and intrusiveness--the excessive expression of maternal behavior--describe distinct and stable maternal styles that bear long-term consequences for infant well-being. To integrate brain, hormones, and behavior in the study of maternal-infant bonding, we examined the fMRI responses of synchronous vs intrusive mothers to dynamic, ecologically valid infant videos and their correlations with plasma Oxytocin. In all, 23 mothers were videotaped at home interacting with their infants and plasma OT assayed. Sessions were micro-coded for synchrony and intrusiveness. Mothers were scanned while observing several own and standard infant-related vignettes. Synchronous mothers showed greater activations in the left nucleus accumbens (NAcc) and intrusive mothers exhibited higher activations in the right amygdala. Functional connectivity analysis revealed that among synchronous mothers, left NAcc and right amygdala were functionally correlated with emotion modulation, theory-of-mind, and empathy networks. Among intrusive mothers, left NAcc and right amygdala were functionally correlated with pro-action areas. Sorting points into neighborhood (SPIN) analysis demonstrated that in the synchronous group, left NAcc and right amygdala activations showed clearer

  8. Recombinant human growth hormone treatment in short children with renal disease: Our first experience

    Directory of Open Access Journals (Sweden)

    Spasojević-Dimitrijeva Brankica

    2010-01-01

    Full Text Available Introduction. Growth retardation is a hallmark of chronic illnesses such as chronic kidney disease in children, and it is associated with increased morbidity and mortality. The growth hormone (GH resistance observed in uraemia can be overcome by supraphysiological doses of exogenous GH. Objective. We would like to present our first results of recombinant human growth hormone (rhGH treatment, mainly in children on haemodialysis. Methods. Sixteen children, aged 4.5-17.1 years (mean age 11.25±3.57 with height below -2.0 standard deviation score (SDS for age or height velocity below -2.0 SDS for age, were selected to receive rhGH therapy at our Nephrology and Haemodialysis Department. Most of them were on haemodialysis (14 children with mean spent time 2.88±2.68 years (0-9 years before the initiation of rhGH therapy. One half of patients were prepubertal (8 children and the second half were in early puberty (testicular volume between 4 and 8 ml for boys and breast development B2 or B3 in girls. All patients received 28-30IU/m² rhGH per week by daily subcutaneous injection. The year before rhGH therapy served as a control period. Results. During the first year of treatment, mean height velocity in haemodialysis patients increased from 2.25 cm/year to 6.59 cm/year (p<0.0001 and in the second year it was 5.25 cm/ year (p=0.004. The mean height SDS in haemodialysis children did not improve significantly during the first year of rhGH treatment (from -3.01 SDS to -2.77 SDS, p=0.063. Neither weight nor the body mass index varied compared with the pretreatment period. Two patients developed worsened secondary hyperparathyroidism and were excluded from the study, but the relationship with rhGH remains uncertain. Conclusion. Mean height velocity significantly improved during rhGH therapy in haemodialysis patients. No significant side-effects were observed in children during three-year treatment with GH.

  9. Quantitative analysis of steroid hormones in human hair using a column-switching LC-APCI-MS/MS assay.

    Science.gov (United States)

    Gao, Wei; Stalder, Tobias; Foley, Paul; Rauh, Manfred; Deng, Huihua; Kirschbaum, Clemens

    2013-06-01

    The analysis of steroid hormones in hair is increasingly used in the field of stress-related research to obtain a retrospective index of integrated long-term hormone secretion. Here, most laboratories have so far relied on immunochemical assays originally developed for salivary analyses. Although these assays are fast and easy to perform, they have a reduced reliability and specificity due to cross-reactivity with other substances and are limited to the detection of one hormone at a time. Here, we report the development of a LC-MS/MS-based method for simultaneous identification of endogenous concentrations of seven steroid hormones (cortisol, cortisone, testosterone, progesterone, corticosterone, dehydroepiandrosterone (DHEA) and androstenedione) in human hair. Hair samples were washed with isopropanol and steroid hormones were extracted from 10mg whole, nonpulverized hair by methanol incubation. A column switching strategy for on-line solid phase extraction (SPE) was applied, followed by analyte detection on an AB Sciex API 5000 QTrap mass spectrometer. Results indicated linearity of the method for all steroids over ranges of 0.09-90pg/mg (0.9-900pg/mg for DHEA) with correlation coefficients ranging between 0.9995 and 0.9999. Intra- and inter-assay coefficients of variation were between 3.7 and 9.1%. The limits of quantification (LOQ) were below (or equal to) 0.1pg/mg for all steroids, except of DHEA for which the LOQ was 0.9pg/mg. An analysis of 30 natural hair samples (15 men/15 women) using this method confirmed that all steroid hormones could be quantified at endogenous levels in each individual. In addition, the use of whole hair samples and on-line SPE resulted in a significant reduction in sample throughput times, increasing the applicability of this method for research questions where a larger number of samples needs to be processed.

  10. Identification of the human P450 enzymes involved in the in vitro metabolism of the synthetic steroidal hormones Org 4060 and Org 30659

    NARCIS (Netherlands)

    Verhoeven, CHJ; Van Munster, TTM; Groothuis, GMM; Vos, RME; Rietjens, IMCM

    2002-01-01

    1. The type of human P450 enzymes involved in the in vitro metabolism of Org 4060 and Org 30659, two synthetic steroidal hormones currently under clinical development by NV Organon for use in oral contraceptive and hormone replacement therapy, was investigated. 2. Both steroids were mainly hydroxyla

  11. Model-based process development for the purification of a modified human growth hormone using multimodal chromatography.

    Science.gov (United States)

    Sejergaard, Lars; Karkov, Hanne Sophie; Krarup, Janus Kristian; Hagel, Anne Birgitte Bagge; Cramer, Steven M

    2014-01-01

    This study demonstrates how the multimodal Capto adhere resin can be used in concert with calcium chloride or arginine hydrochloride as mobile phase modifiers to create a highly selective purification process for a modified human growth hormone. Importantly, these processes are shown to result in significant clearance of product related aggregates and host cell proteins. Furthermore, the steric mass action model is shown to be capable of accurately describing the chromatographic process and the aggregate removal. Finally, justification of the selected operating ranges is evaluated using the model together with Latin hypercube sampling. The results in this article establish the utility of multimodal chromatography when used with appropriate mobile phase modifiers for the downstream bioprocessing of a modified human growth hormone and offer new approaches for bioprocess verification.

  12. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    Energy Technology Data Exchange (ETDEWEB)

    Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))

    1989-06-01

    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  13. [Thyroid hormones and cardiovascular system].

    Science.gov (United States)

    Límanová, Zdeňka; Jiskra, Jan

    Cardiovascular system is essentially affected by thyroid hormones by way of their genomic and non-genomic effects. Untreated overt thyroid dysfunction is associated with higher cardiovascular risk. Although it has been studied more than 3 decades, in subclinical thyroid dysfunction the negative effect on cardiovascular system is much more controversial. Large meta-analyses within last 10 years have shown that subclinical hyperthyroidism is associated with higher cardiovascular risk than subclinical hypothyroidism. Conversely, in patients of age > 85 years subclinical hypothyroidism was linked with lower mortality. Therefore, subclinical hyperthyroidism should be rather treated in the elderly while subclinical hypothyroidism in the younger patients and the older may be just followed. An important problem on the border of endocrinology and cardiology is amiodarone thyroid dysfunction. Effective and safe treatment is preconditioned by distinguishing of type 1 and type 2 amiodarone induced hyperthyroidism. The type 1 should be treated with methimazol, therapeutic response is prolonged, according to recent knowledge immediate discontinuation of amiodarone is not routinely recommended and patient should be usually prepared to total thyroidectomy, or rather rarely 131I radioiodine ablation may be used if there is appropriate accumulation. In the type 2 there is a promt therapeutic response on glucocorticoids (within 1-2 weeks) with permanent remission or development of hypothyroidism. If it is not used for life-threatening arrhytmias, amiodarone may be discontinuated earlier (after several weeks). Amiodarone induced hypothyroidism is treated with levothyroxine without amiodarone interruption.Key words: amiodarone induced thyroid dysfunction - atrial fibrillation - cardiovascular risk - heart failure - hyperthyroidism - hypothyroidism - thyroid stimulating hormone.

  14. Studying the Anti-aging Effect of Human Growth Hormone on Human Fibroblast Cells via Telomerase Activity

    Directory of Open Access Journals (Sweden)

    Nader Chaparzadeh

    2010-01-01

    Full Text Available Objective: In recent years, studies have focused on the telomerase for cancer treatmentby repressing telomerase in cancerous cells or prevent cell aging by activating it in theaged cells. Thus, in these studies natural and synthetic agents have been used to repressor activate telomerase. In this research, we investigated the effects of human growth hormone(hGH on aging via evaluation of telomerase activity.Materials and Methods: Primary human foreskin fibroblast cells were isolated, culturedand treated with different concentrations of hGH. BrdU and MTT cell proliferation assaysand cells number counting. Cell aging was assayed by the senescence sensitivegalactosidase staining method. Telomerase activity was measured with a telomerasePCR ELISA kit.Data were analyzed with SPSS software (one-way ANOVA and univariateANOVA.Results: Our results indicated that cells treated with a lower concentration (0.1, 1 ng/mlof hGH had more green color cells (aged cells. Furthermore, cell proliferation increasedwith increasing hGH concentrations (10 to 100 ng/ml which was significant in comparisonwith untreated control cells. TRAP assay results indicated that telomerase activityincreased with increasing hGH concentration, but there was no significant difference. Additionally,more rapid cell growth and telomerase activity was noted in the absence of H2O2when compared with the presence of H2O2, which was significantly different.Conclusion: Although increasing cell proliferation along with increasing hGH concentrationwas confirmed by all cell proliferation assays, only the cell counting test was statisticallysignificant. Thus, it is inconclusive that hGH (up to 100 ng/ml has an anti-agingeffect. Also, because there was no significant difference in the telomerase activity results(in spite of increasing progress along with increasing hGH concentration we can not certainlyconclude that hGH (up to 100 ng/ml impacts telomerase activity.

  15. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies.

    Science.gov (United States)

    Hsu, S M; Raine, L; Fanger, H

    1981-05-01

    A highly sensitive immunoenzymatic technic is presented. The method involves three sequential steps: (1) primary antibody, (2) biotin-labeled secondary antibody, and (3) avidin-biotin-peroxidase complex. Avidin, an egg white protein, has four binding sites for the low-molecular-weight vitamin biotin. Many moieties of biotin can be coupled to the peroxidase molecule. Thus, since a relatively large amount of avidin is incubated with biotin-labeled peroxidase, avidin serves as a link between biotin-peroxidase molecules; in turn, biotin-peroxidase serves as a link between avidin molecules. Consequently, this large lattice-like complex with biotin-binding capability can be attracted to the sites of biotin-labeled antibody, producing a superior staining sensitivity. Several commercially available radioimmunoassay antibodies (e.g., antiglucagon, prolactin, gastrin, growth hormone, and thyroid-stimulating hormone antibodies) were tested for immunohistochemical staining. The unlabeled antibody peroxidase-antiperoxidase method fails to stain gastrin or thyroid-stimulating secretory cells when using these antibodies, and a relatively high antibody concentration is required to produce a positive reaction for glucagon, prolactin, and growth hormone. In contrast, the avidin-biotin-peroxidase complex method successfully demonstrates polypeptide hormones even when antibodies are diluted 20 to 40 times.

  16. Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

    Science.gov (United States)

    RATIONALE: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and gluoose intolerance that are assoc...

  17. Hormonal and Dietary Characteristics in Obese Human Subjects with and without Food Addiction

    OpenAIRE

    Pardis Pedram; Guang Sun

    2014-01-01

    The concept of food addiction (FA) is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 73...

  18. Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans.

    Science.gov (United States)

    Butler, P; Kryshak, E; Rizza, R

    1991-04-01

    Growth hormone excess can cause postprandial carbohydrate intolerance. To determine the contribution of splanchnic and extrasplanchnic tissues to this process, subjects were fed an isotopically labeled mixed meal after either a 12-h infusion of saline or growth hormone (4 micrograms.kg-1.h-1 [corrected]). Growth hormone infusion resulted in higher glucose and insulin concentrations both before and after meal ingestion. Despite growth hormone-induced hyperglycemia and hyperinsulinemia, postprandial hepatic glucose release and carbon dioxide incorporation into glucose (a qualitative estimate of gluconeogenesis) were similar to those present during saline, suggesting altered hepatic regulation. This was confirmed when glucose was infused in the absence of growth hormone to achieve glucose (and insulin) concentrations comparable to those present during growth hormone infusion. Although growth hormone excess did not alter splanchnic uptake of ingested glucose, it resulted in a fivefold increase in postprandial hepatic glucose release (578 +/- 31 vs. 117 +/- 10 mg.kg-16 h-1, P less than 0.01), less suppression of carbon dioxide incorporation into glucose (-13 +/- 9 vs. -53 +/- 12 mg.kg-1. 6-h-1, P less than 0.01), and lower glucose uptake (1,130 +/- 59 vs. 1,850 +/- 150 mg.kg-1.6 h-1, P less than 0.01). The decrease in postprandial glucose uptake did not appear to be mediated by a change in substrate uptake since postprandial plasma concentrations and forearm balance of lactate, free fatty acids, and ketone bodies did not differ in the presence and absence of growth hormone excess.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Effects of human growth hormone on the catabolic state after surgical trauma.

    Science.gov (United States)

    Vara-Thorbeck, R; Ruiz-Requena, E; Guerrero-Fernández, J A

    1996-01-01

    The aims of our studies were: (1) to determine if the protein catabolic response after a major or moderate surgical trauma can be restrained by the administration of exogenous human growth hormone (hGH); (2) to determine if the administration of hGH can improve systemic host defenses, thus reducing the risk of infection, and (3) given that the postoperative fatigue syndrome (POF) is mediated by the endocrino-metabolic response to surgery we attempt to determine if the administration of hGH can prevent or reduce POF. Therefore, we performed three placebo-controlled randomized double-blind trials on 216 patients. Major gastrointestinal surgery was treated only with total parenteral nutrition (TPN; n = 20) or TPN plus 4 IU hGH (n = 18). Patients with moderate surgical trauma received either hypocaloric parenteral nutrition (HPN; n = 93) or HPN and 8 IU hGH (n = 87). In this study, we also determined the evolution of the systemic host defenses and thereby the risk of infection. In 48 patients who underwent cholecystectomy treated (n = 26) either with HPN or HPN plus 8 IU hGH, we measured the protein catabolic response, postoperative fatigue and anthropometric modifications. The treatment with hGH together with HPN or TPN (1) overcomes the protein catabolic effects of the trauma response induced by major or moderate surgery by increasing protein synthesis, (2) improves humoral and cellular systemic host defenses, thus reducing the risk of infection, (3) preserves or increases lean body mass and reduces adipose tissue and (4) minimizes POF.

  20. Response of the growth plate of uremic rats to human growth hormone and corticosteroids

    Directory of Open Access Journals (Sweden)

    A.P.F. Barbosa

    2007-08-01

    Full Text Available Children with chronic renal failure in general present growth retardation that is aggravated by corticosteroids. We describe here the effects of methylprednisolone (MP and recombinant human growth hormone (rhGH on the growth plate (GP of uremic rats. Uremia was induced by subtotal nephrectomy in 30-day-old rats, followed by 20 IU kg-1 day-1 rhGH (N = 7 or 3 mg kg-1 day-1 MP (N = 7 or 20 IU kg-1 day-1 rhGH + 3 mg kg-1 day-1 MP (N = 7 treatment for 10 days. Control rats with intact renal function were sham-operated and treated with 3 mg kg-1 day-1 MP (N = 7 or vehicle (N = 7. Uremic rats (N = 7 were used as untreated control animals. Structural alterations in the GP and the expression of anti-proliferating cell nuclear antigen (PCNA and anti-insulin-like growth factor I (IGF-I by epiphyseal chondrocytes were evaluated. Uremic MP rats displayed a reduction in the proliferative zone height (59.08 ± 4.54 vs 68.07 ± 7.5 µm, P < 0.05 and modifications in the microarchitecture of the GP. MP and uremia had an additive inhibitory effect on the proliferative activity of GP chondrocytes, lowering the expression of PCNA (19.48 ± 11.13 vs 68.64 ± 7.9% in control, P < 0.0005 and IGF-I (58.53 ± 0.96 vs 84.78 ± 2.93% in control, P < 0.0001, that was counteracted by rhGH. These findings suggest that in uremic rats rhGH therapy improves longitudinal growth by increasing IGF-I synthesis in the GP and by stimulating chondrocyte proliferation.

  1. Comparison of human growth hormone products' cost in pediatric and adult patients. A budgetary impact model.

    Science.gov (United States)

    Bazalo, Gary R; Joshi, Ashish V; Germak, John

    2007-09-01

    We assessed the economic impact to the United States payer of recombinant human growth hormone (rhGH) utilization, comparing the relative dosage efficiency of marketed pen-based and vial-based products in a pediatric and in an adult population. A budgetary impact model calculated drug costs based on product waste and cost. Waste was the difference between prescribed dose, based on patient weight, and actual delivered dose, based on dosing increments and maximum deliverable dose for pens and a fixed-percent waste as derived from the literature for vials. Annual wholesale acquisition costs were calculated based upon total milligrams delivered, using a daily dose of 0.03 mg/kg for pediatric patients and 0.016 mg/kg for adults. Total annual drug costs were compared for two scenarios: 1) a product mix based on national market share and 2) restricting use to the product with lowest waste. Based on the literature, waste for each vial product was 23 percent. Among individual pens, waste was highest for Humatrope 24 mg (19.5 percent pediatric, 14.3 percent adult) and lowest for Norditropin Nordi-Flex 5 mg (1.1 percent pediatric, 1 percent adult). Restricting use to the brand with least waste (Norditropin), compared to national product share mix, resulted in a 10.2 percent reduction in annual pediatric patient cost from $19,026 to $17,089 and an 8 percent reduction in annual adult patient cost from $24,099 to $22,161. We concluded that pen delivery systems result in less waste than vial and syringe. Considering all approved delivery systems, Norditropin resulted in the least product waste and lower annual patient cost for both pediatric and adult populations.

  2. Improved Cardiac Contractility of Human Recombinant Growth Hormone on the Congestive Heart Failure of Pig

    Institute of Scientific and Technical Information of China (English)

    Yang Ping; He Yu-quan; Zeng Hong; Ni Jin-song; Yun Qing-jun; Huang Xiao-ping; Li Shu-mei

    2005-01-01

    The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig's body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41 ) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56 ±0.18) L/min in the saline control group (P<0.05); Peripheral min) -1 in the saline control group (P<0.05); ± dp/dtmax was (2900 ±316.23) and (2280 ±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.

  3. Ten years of clinical experience with biosimilar human growth hormone: a review of safety data.

    Science.gov (United States)

    Borrás Pérez, Maria Victoria; Kriström, Berit; Romer, Tomasz; Walczak, Mieczyslaw; Höbel, Nadja; Zabransky, Markus

    2017-01-01

    Safety concerns for recombinant human growth hormone (rhGH) treatments include impact on cancer risk, impact on glucose homeostasis, and the formation of antibodies to endogenous/exogenous GH. Omnitrope(®) (biosimilar rhGH) was approved by the European Medicines Agency in 2006, with approval granted on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin(®)). Additional concerns that may exist in relation to biosimilar rhGH include safety in indications granted on the basis of extrapolation and the impact of changing to biosimilar rhGH from other rhGH treatments. A substantial data set is available to fully understand the safety profile of biosimilar rhGH, which includes data from its clinical development studies and 10 years of post-approval experience. As of June 2016, 106,941,419 patient days (292,790 patient-years) experience has been gathered for biosimilar rhGH. Based on the available data, there have been no unexpected or unique adverse events related to biosimilar rhGH treatment. There is no increased risk of cancer, adverse glucose homeostasis, or immunogenic response with biosimilar rhGH compared with the reference medicine and other rhGH products. The immunogenicity of biosimilar rhGH is also similar to that of the reference and other rhGH products. Physicians should be reassured that rhGH products have a good safety record when used for approved indications and at recommended doses, and that the safety profile of biosimilar rhGH is in keeping with that of other rhGH products.

  4. Development of a sustained-release recombinant human growth hormone formulation.

    Science.gov (United States)

    Kwak, H H; Shim, W S; Choi, M K; Son, M K; Kim, Y J; Yang, H C; Kim, T H; Lee, G I; Kim, B M; Kang, S H; Shim, C K

    2009-07-20

    Recombinant human growth hormone (rhGH) therapy for short stature must be administered as a daily injection because of its poor bioavailability and short half-life. In the present study, a sustained-release formulation of rhGH (SR-rhGH), DA-3003, was prepared using double emulsion solvent evaporation with poly(D,L-lactide-co-glycolide) (PLGA), zinc oxide and hydroxypropyl-beta-cyclodextrin (HPCD) as the release modulator, stabilizer, and aggregation-prevention agent, respectively. After a single administration of DA-3003, the elevated concentration of rhGH in plasma was sustained for 14 days in rats and 28 days in monkeys. The plasma concentration of insulin-like growth factor-1 (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), which are pharmacodynamic markers of rhGH administration, increased and remained elevated for approximately 28 days in monkeys. Monkeys administered DA-3003 did not develop antibodies to hGH, indicating safety of the SR-rhGH formulation comparable to that observed with daily rhGH injections (Growtropin II). There were no significant differences in efficacy between Growtropin II (daily dose of 5 microg/animal for 14 days) and DA-3003 (weekly dose of 35 microg/animal for 14 days with a dosing interval of a week) in hypophysectomized rats, as assessed by changes in body weight and the width of the tibial growth plate. These results show that a sustained-release rhGH formulation, DA-3003, has the potential to be used safely and efficaciously in a weekly dosing regimen.

  5. Osteopontin but not parathyroid hormone-related protein predicts prognosis in human renal cell carcinoma.

    Science.gov (United States)

    Papworth, Karin; Bergh, Anders; Grankvist, Kjell; Ljungberg, Börje; Sandlund, Johanna; Rasmuson, Torgny

    2013-01-01

    To evaluate the relationship between osteopontin (OPN) in serum and plasma and parathyroid hormone-related protein (PTHrP) in serum, plasma and tumour tissue, and to assess the prognostic impact of OPN and PTHrP in human renal cell carcinoma (RCC). The study included 269 patients with RCC. In 189 patients, immunohistochemical (IHC) PTHrP tumour tissue expression was evaluated, and OPN and PTHrP in serum were assessed. In 80 patients, plasma OPN and PTHrP were analysed. Tumour type, TNM stage, nuclear grade and RCC-specific survival were also registered. In a sub-group, IHC expression of CD 31 was assessed. The prognostic information of the factors was analysed using uni- and multivariate analyses. The median OPN level was 2.3 times higher in plasma than in serum. Serum OPN was significantly higher in patients with papillary RCC compared to clear cell RCC and chromophobe RCC. Both serum and plasma OPN levels were positively correlated to TNM stage and nuclear grade. Multivariate analysis showed that serum and plasma OPN levels were independent prognostic factors for RCC-specific survival, along with TNM stage. Immunohistochemical expression of PTHrP associated to TNM stage but not to nuclear grade or serum OPN. Furthermore, IHC expression of PTHrP was positively correlated to serum PTHrP but inversely to tumour CD31 expression. Plasma PTHrP was increased in 20% of the patients and related to TNM stage but not to nuclear grade. Plasma OPN was significantly higher in patients with increased PTHrP levels, compared to those with normal levels. Plasma OPN levels differed between RCC types, and in clear cell RCC, both serum and plasma OPN levels were independent predictors of survival. We found no evidence for prognostic value related to circulating levels or the IHC expression of PTHrP.

  6. Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans

    Energy Technology Data Exchange (ETDEWEB)

    Horber, F.F.; Marsh, H.M.; Haymond, M.W. (Mayo Clinic, Rochester, MN (USA))

    1991-01-01

    Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation {sup 14}C leucine increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment.

  7. Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.

    Science.gov (United States)

    Kim, Su Jin; Kwak, Hyun-Hee; Cho, Sung Yoon; Sohn, Young Bae; Park, Sung Won; Huh, Rimm; Kim, Jinsup; Ko, Ah-Ra; Jin, Dong-Kyu

    2015-10-05

    The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.

  8. Transgenic expression of the human growth hormone minigene promotes pancreatic β-cell proliferation.

    Science.gov (United States)

    Baan, Mieke; Kibbe, Carly R; Bushkofsky, Justin R; Harris, Ted W; Sherman, Dawn S; Davis, Dawn Belt

    2015-10-01

    Transgenic mouse models are designed to study the role of specific proteins. To increase transgene expression the human growth hormone (hGH) minigene, including introns, has been included in many transgenic constructs. Until recently, it was thought that the hGH gene was not spliced, transcribed, and translated to produce functional hGH protein. We generated a transgenic mouse with the transcription factor Forkhead box M1 (FoxM1) followed by the hGH minigene, under control of the mouse insulin promoter (MIP) to target expression specifically in the pancreatic β-cell. Expression of FoxM1 in isolated pancreatic islets in vitro stimulates β-cell proliferation. We aimed to investigate the effect of FoxM1 on β-cell mass in a mouse model for diabetes mellitus. However, we found inadvertent coexpression of hGH protein from a spliced, bicistronic mRNA. MIP-FoxM1-hGH mice had lower blood glucose and higher pancreatic insulin content, due to increased β-cell proliferation. hGH signals through the murine prolactin receptor, and expression of its downstream targets tryptophan hydroxylase-1 (Tph1), tryptophan hydroxylase-2 (Tph2), and cytokine-inducible SH2 containing protein (Cish) was increased. Conversely, transcriptional targets of FoxM1 were not upregulated. Our data suggest that the phenotype of MIP-FoxM1-hGH mice is due primarily to hGH activity and that the FoxM1 protein remains largely inactive. Over the past decades, multiple transgenic mouse strains were generated that make use of the hGH minigene to increase transgene expression. Our work suggests that each will need to be carefully screened for inadvertent hGH production and critically evaluated for the use of proper controls.

  9. Conformational origin of a difficult coupling in a human growth hormone releasing factor analog.

    Science.gov (United States)

    Deber, C M; Lutek, M K; Heimer, E P; Felix, A M

    1989-01-01

    During the solid-phase synthesis of the human growth hormone releasing factor (GRF) analog [Ala15, Leu27, Asn28] -GRF(1-32)-OH, incorporation of Boc-Gln16 was determined to be incomplete. While aggregation of growing resin-bound peptide chains with concomitant beta-sheet formation and "precipitation" has been proposed to account in general for such "difficult coupling," no feature of sequence in the Gln16 region of this GRF analog provided an immediate rationale for this result. We now report 500 MHz 1H NMR spectra of a series of resin-bound GRF segments surrounding the Gln16 position (19-32 through 14-32), swelled in dimethylsulfoxide-d6 solutions [GRF(14-32) = Leu14-Ala-Gln-Leu-Ser(Bzl)-Ala-Arg(Tos)-Lys(CIZ)-Leu- Leu-Gln-Asp(OcHex)-Ile-Leu-Asn-Arg(Tos)-Gln-Gln-Gly32-PAM resin]. While relatively sharp spectra are observed for GRF(19-32), components with resonances broadened by an order-of-magnitude appear in spectra of the 18-32 and 17-32 peptide-resin, and the entire spectrum of 16-32 is ill-resolved and highly broadened. Subsequent spectra sharpen again (15-32, 14-32). These combined synthesis/spectroscopic experimental results, in conjunction with predictive analyses using standard Chou-Fasman 2 degrees structure parameters, suggest that the completeness of the Gln16 coupling is hindered by formation of a specific, folded beta-sheet/beta-turn structure in GRF(16-32) (with the turn located at 18-21, "upstream" of the difficult coupling site), and accompanying aggregation of peptide chains. This analysis suggests that awareness of such potential beta-sheet/beta-turn sequences can guide analog choices, and/or facilitate pre-programming of synthesis steps in anticipation of problem couplings.

  10. Stability of Human Follicle-Stimulating Hormone Receptor mRNA in Stably Transfected Cells

    Institute of Scientific and Technical Information of China (English)

    朱长虹; 田红

    2001-01-01

    In order to assess the impact of mRNA degradation on steady state levels of follicle-stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene expression, the stability and half-life of FSHR mRNA were determined in transfected cells expressing recombinant FSHR. Time-dependent changes in FSHR mRNA content were determined by nuclease protection-solution hybridization assay (NPA) or by qualitative reverse transcription-competitive polymerase chain reaction (RT-PCR) in cultured hFSHR-YI cells, cell lines stably transfected with a human FSHR cDNA. FSHR mRNA content remained constant during 8 h control incubations of hFSHR-Y1 cells (NPA, 2.9±0.3 μg/mg RNA; RT-PCR, 2.7±0.3 μg/mg RNA). Actinomycin D (ActD, 5 μg/ml) inhibited mRNA synthesis, as assessed by incorporation of [3 H]uridine into total RNA, by 90 % within 1 h in hFSHR-Y1 cells. No effect of ActD on cellular morphology or viability was observed. ActD caused a time-dependent decrease in FSHR mRNA content in hFSHR-Y1 cell lines with a lag time of 1 h. There were no significant differences in the rate of FSHR mRNA degradation between the two methods of mRNA quantification. The half-life of hFSHR mRNA was 3.6±0.2 h by NPA and 3.1±0.1 h by RT-PCR. The results indicated that degradation of mRNA was an important process in maintenance of steady state expression of the FSHR gene in cells stably expressing recombinant receptor.

  11. Luteinizing Hormone Receptor Knockout (LuRKO) Mice and Transgenic Human Chorionic Gonadotropin (hCG)-Overexpressing Mice (hCG αβ+) Have Bone Phenotypes

    National Research Council Canada - National Science Library

    Yarram, S. J; Perry, M. J; Christopher, T. J; Westby, K; Brown, N. L; Lamminen, T; Rulli, S. B; Zhang, F.-P; Huhtaniemi, I; Sandy, J. R; Mansell, J. P

    2003-01-01

    Considerable attention has been paid to the role of sex steroids during periods of major skeletal turnover, but the interaction of the gonadotropic hormones, which include LH, FSH, and human chorionic gonadotropin (hCG...

  12. Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

    Energy Technology Data Exchange (ETDEWEB)

    Vickers, Alison E.M., E-mail: vickers_alison@allergan.com [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States); Heale, Jason; Sinclair, John R.; Morris, Stephen; Rowe, Josh M. [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States); Fisher, Robyn L. [Vitron Inc., Tucson, AZ (United States)

    2012-04-01

    Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ≥ 10 μM MMI. Thyroid from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (∼ 15–84 μM), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (≥ 10 μM) and PTU (100 μM). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ∼ 2-fold) and only at higher MMI concentrations (≥ 1500 μM, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ► Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ► TPO inhibition by MMI or PTU altered

  13. Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor-1, is positively associated with fetal growth in the first half of pregnancy

    DEFF Research Database (Denmark)

    Pedersen, N G; Juul, A; Christiansen, M

    2010-01-01

    To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy.......To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy....

  14. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

    Directory of Open Access Journals (Sweden)

    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  15. Earthing the human body influences physiologic processes.

    Science.gov (United States)

    Sokal, Karol; Sokal, Pawel

    2011-04-01

    This study was designed to answer the question: Does the contact of the human organism with the Earth via a copper conductor affect physiologic processes? Subjects and experiments: Five (5) experiments are presented: experiment 1-effect of earthing on calcium-phosphate homeostasis and serum concentrations of iron (N = 84 participants); experiment 2-effect of earthing on serum concentrations of electrolytes (N = 28); experiment 3-effect of earthing on thyroid function (N = 12); experiment 4-effect of earthing on glucose concentration (N = 12); experiment 5-effect of earthing on immune response to vaccine (N = 32). Subjects were divided into two groups. One (1) group of people was earthed, while the second group remained without contact with the Earth. Blood and urine samples were examined. Earthing of an electrically insulated human organism during night rest causes lowering of serum concentrations of iron, ionized calcium, inorganic phosphorus, and reduction of renal excretion of calcium and phosphorus. Earthing during night rest decreases free tri-iodothyronine and increases free thyroxine and thyroid-stimulating hormone. The continuous earthing of the human body decreases blood glucose in patients with diabetes. Earthing decreases sodium, potassium, magnesium, iron, total protein, and albumin concentrations while the levels of transferrin, ferritin, and globulins α1, α2, β, and γ increase. These results are statistically significant. Earthing the human body influences human physiologic processes. This influence is observed during night relaxation and during physical activity. Effect of the earthing on calcium-phosphate homeostasis is the opposite of that which occurs in states of weightlessness. It also increases the activity of catabolic processes. It may be the primary factor regulating endocrine and nervous systems.

  16. A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

    Science.gov (United States)

    Januszkiewicz, A; Essén, P; McNurlan, M A; Ringdén, O; Garlick, P J; Wernerman, J

    2001-11-01

    In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

  17. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel;

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP......Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim...

  18. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel;

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP......Fatty acid-induced damage in pancreatic ß-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve ß-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim...

  19. A Prospective Investigation of Graves' Disease and Selenium: Thyroid Hormones, Auto-Antibodies and Self-Rated Symptoms

    DEFF Research Database (Denmark)

    Calissendorff, Jan; Mikulski, Emil; Larsen, Erik Huusfeldt

    2015-01-01

    Background: In Graves' thyrotoxicosis tachycardia, weight loss and mental symptoms are common. Recovery takes time and varies between patients. Treatment with methimazole reduces thyroid hormone levels. According to previous research, this reduction has been faster if selenium (Se) is added....... Objective: The objective was to investigate whether supplementing the pharmacologic treatment with Se could change the immune mechanisms, hormone levels and/or depression and anxiety. Methods: We prospectively investigated 38 patients with initially untreated thyrotoxicosis by measuring the thyroid......-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid receptor antibodies and thyroid peroxidase auto-antibodies before medication and at 6, 18 and 36 weeks after commencing treatment with methimazole and levo-thyroxine, with a randomized blinded oral administration of 200 µg Se...

  20. Recombinant human TSH in differentiated thyroid cancer: a nuclear medicine perspective

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, P. [CEA, DSV, I2BM, SHFJ, LMNRB, Orsay (France); Rubello, D. [Osped S Maria Misericordia, IRCCS, IOV, Dept Nucl Med, PET Ctr, I-45100 Rovigo (Italy); Hindie, E. [Hop St Louis, Dept Nucl Med, Paris (France)

    2008-07-01

    The use of recombinant human thyroid-stimulating hormone (rhTSH) in differentiated thyroid cancer (DTC) is widely discussed in the literature with regard to the diagnostic and therapeutic aspects of the management of DTC patients. However, some controversy about the appropriate indications, advantages and potential disadvantages of the use of rhTSH may still exist within the community of nuclear medicine physicians. In our opinion, the clinical benefits of rhTSH in avoiding hypothyroidism outweigh its somewhat lesser diagnostic accuracy. However, we disagree on designating rhTSH as the 'golden standard' to obtain TSH stimulation, as suggested by some authors. Thus, the first follow-up examination after ablation, which is determinant for patients' prognostic classification, can be either done under rhTSH stimulation or after hormone withdrawal. In our practice, and for higher risk patients, we still favour performing the initial follow-up after thyroid hormone withdrawal. rhTSH also shows the ability to enhance radioiodine concentration into thyroid cells. This characteristic is obviously of great interest among the nuclear medicine community. In clinical practice, it seems preferable to perform {sup 131}I treatment for metastatic disease during hypothyroidism. rhTSH may find its utility for the treatment of specific populations of patients, i.e. those in whom hormone withdrawal is medically contraindicated or in whom adequate endogenous TSH levels cannot be obtained due to reduced pituitary reserve or continued thyroxine production by metastatic tissue. In conclusion, rhTSH has demonstrated to be a reliable alternative to hypothyroidism for the stimulation of Tg in the follow-up of thyroid cancer patients. However, its use must be more carefully chosen in the therapeutic setting. Our feeling is that rhTSH should no tbe used for remnant ablation in high-risk patients and for the treatment of metastatic disease, except for specific populations of

  1. Hormones and Antibiotics in Nature: A Laboratory Module Designed to Broaden Undergraduate Perspectives on Typically Human-Centered Topics

    Directory of Open Access Journals (Sweden)

    Carolyn F. Weber

    2014-07-01

    Full Text Available Bringing discovery-based research into undergraduate laboratory courses increases student motivation and learning gains over traditional exercises that merely teach technique or demonstrate well-documented phenomena. Laboratory experiences are further enhanced when they are designed to challenge student perspectives on topics relevant to their lives. To this end, a laboratory module on antibiotics and hormones, which are generally discussed in the context of human health, was developed for students to explore the multifaceted roles of antibiotics and hormones in nature (e.g. interspecies communication via reading primary scientific literature and performing discovery-based experiments. The main objective of this module was to increase the general biological literacy of students as determined by their ability to connect the Five Core Concepts of Biological Literacy (American Association for the Advancement of Science, Vision and Change in Undergraduate Education: A Call to Action, 2011 to the topics “hormones” and “antibiotics” in pre- and postmodule surveys. After discussing unpublished research findings, cell biology students performed experiments demonstrating that: 1 fungi may promote fern growth via hormone production, 2 novel bacterial isolates in the genus Streptomyces produce antifungal compounds, and 3 subinhibitory antibiotic concentrations may enhance soil bacterial growth. The third finding provided evidence supporting a hypothesis framed in a scientific article that students read and discussed. Student perspectives on premodule surveys focused on roles of hormones and antibiotics in the human body (e.g. development, fighting infection, but their broadened postmodule perspectives encompassed the roles of these molecules in organismal communication and possibly the evolution of multicellularity.

  2. Effect of mirtazapine on thyroid hormones in adult patients with major depression.

    Science.gov (United States)

    Gambi, F; De Berardis, D; Sepede, G; Campanella, D; Galliani, N; Carano, A; La Rovere, L; Salini, G; Penna, L; Cicconetti, A; Spinella, S; Quartesan, R; Salerno, R M; Ferro, F M

    2005-01-01

    Hypothalamic pituitary thyroid (HPT) axis abnormalities and alterations in major depression are reported in the literature. The aim of our study was to evaluate the effect of mirtazapine on thyroid hormones after 6 months of therapy in a sample of adult outpatients with Major Depression (MD). 17 adult outpatients (7 men, 10 women) with MD according to DSM-IV criteria, were included in the study. All participants had to have met criteria for a major depressive episode with a score of at least 15 on the Hamilton Depression Rating Scale (HAM-D). Fasting venous blood samples were obtained for determination of serum Thyroid Stimulating Hormone (TSH), Free T3 (FT3) and Free T4 (FT4) concentrations both at baseline and after 6 months of therapy. HAM-D scores decreased significantly from the first day of treatment to the end of the treatment period (Pdeiodination process of T4 into T3.

  3. The CSF and arterial to internal jugular venous hormonal differences during exercise in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ott, Peter; Dela, Flemming

    2004-01-01

    the brain (a-v diff) of hormones that could influence its carbohydrate uptake (n= 9). In addition, neuroendocrine activity and a potential uptake of hormones via the cerebrospinal fluid (CSF) were assessed by lumbar puncture postexercise and at rest (n= 6). Exercise increased the arterial concentration...... protein (HSP72), insulin, or insulin-like growth factor (IGF)-I. The findings indicate that for maximal exercise, the concentration of noradrenaline is increased within the brain, whereas blood borne hormones and cytokines are seemingly unimportant. The results support the notion that the exercise......Strenuous exercise increases the cerebral uptake of carbohydrate out of proportion to that of oxygen, but it is unknown whether such enhanced carbohydrate uptake is influenced by the marked endocrine response to exercise. During exhaustive exercise this study evaluated the a-v differences across...

  4. Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice.

    Directory of Open Access Journals (Sweden)

    Rebecca C Klein

    Full Text Available The human apolipoprotein ε4 allele (APOE4 has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD.

  5. [Prolactin and thyrotropin after stimulation by thyrotropin releasing hormone a study under long-term administration of oral contraceptives (author's transl)].

    Science.gov (United States)

    Bellmann, O; Bröschen-Zywietz, C; Fichte, K

    1978-02-22

    The longtime application of oral contraceptives is assumed to elevate serum prolactin levels under non-stimulated conditions. We therefore examined whether oral contraceptives also will augment prolactin secretion after stimulation, e.g. by thyrotropin releasing hormone (TRH). After TRH stimulation the time sequence of secretion both of prolactin (HPRL) and thyroid stimulating hormone (TSH) was determined. Three groups of women were tested in a non-randomized study: group 1 without any hormonal medication (= controls), group 2 taking an oral contraceptives containing cyproterone acetate, group 3 using an oral contraceptive containing d-norgestrel. HPRL secretion was similar in all three groups, the same held true for TSH. A possible correlation between the secretion of HPRL and TSH was examined in the control group. No such correlation was found. The secretion patterns of both hormones also were different. In addition, the basic levels of both HPRL and TSH did not seem to influence the response after stimulation.

  6. Thyroid hormone synthesis and secretion in humans after 80 milligrams of iodine for 15 days and subsequent withdrawal.

    Science.gov (United States)

    Theodoropoulou, Anastasia; Vagenakis, Apostolos G; Makri, Maria; Markou, Kostas B

    2007-01-01

    In animals, acute iodine administration results in acute intrathyroidal inhibition of iodinations followed by escape of the inhibition if the excessive iodine intake continues. In humans, the intrathyroidal nonhormonal and hormonal iodine concentration after exposure to large doses of iodine for a relatively long period of time is not known. To determine whether, in human thyroid, administration of large doses of iodine for a relatively long time results in alterations of intrathyroidal hormonal (HI) T4 and T3 and total iodine (TI) content, as well as whether changes in serum concentration of thyroid hormones and TSH would occur after iodine administration or discontinuation. In 33 euthyroid patients with single thyroid nodule or hyperparathyroidism, Lugol solution (80 mg iodine) was administered for 15 d before operation. Groups of six to eight patients underwent operation 0, 5, 10, and 15 d after iodine withdrawal. TI, HI in a sample of thyroid tissue, and serum concentration of T4, T3, and TSH were measured. In 21 normal euthyroid subjects who did not undergo operation, a similar protocol was used and serial blood measurements were taken. Intrathyroidal TI, HI, and serum thyroid hormone and TSH measurements were the main outcome measure. Intrathyroidal HI content and serum T4 and T3 were unchanged during and after iodine discontinuation. TI was increased during iodine administration and returned to control values 5 d after discontinuation of iodine. The ratio of HI/TI was decreased and returned to control values 15 d after the iodine was discontinued. Serum TSH was increased during iodine administration and returned to control values 10 d after iodine withdrawal. In humans, administration of iodine for a relatively long period of time was accompanied by increased intrathyroidal TI, but no changes in HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined

  7. Metabolism of Oral Turinabol by Human Steroid Hormone-Synthesizing Cytochrome P450 Enzymes.

    Science.gov (United States)

    Schiffer, Lina; Brixius-Anderko, Simone; Hannemann, Frank; Zapp, Josef; Neunzig, Jens; Thevis, Mario; Bernhardt, Rita

    2016-02-01

    The human mitochondrial cytochrome P450 enzymes CYP11A1, CYP11B1, and CYP11B2 are involved in the biosynthesis of steroid hormones. CYP11A1 catalyzes the side-chain cleavage of cholesterol, and CYP11B1 and CYP11B2 catalyze the final steps in the biosynthesis of gluco- and mineralocorticoids, respectively. This study reveals their additional capability to metabolize the xenobiotic steroid oral turinabol (OT; 4-chlor-17β-hydroxy-17α-methylandrosta-1,4-dien-3-on), which is a common doping agent. By contrast, microsomal steroid hydroxylases did not convert OT. Spectroscopic binding assays revealed dissociation constants of 17.7 µM and 5.4 µM for CYP11B1 and CYP11B2, respectively, whereas no observable binding spectra emerged for CYP11A1. Catalytic efficiencies of OT conversion were determined to be 46 min(-1) mM(-1) for CYP11A1, 741 min(-1) mM(-1) for CYP11B1, and 3338 min(-1) mM(-1) for CYP11B2, which is in the same order of magnitude as for the natural substrates but shows a preference of CYP11B2 for OT conversion. Products of OT metabolism by the CYP11B subfamily members were produced at a milligram scale with a recombinant Escherichia coli-based whole-cell system. They were identified by nuclear magnetic resonance spectroscopy to be 11β-OH-OT for both CYP11B isoforms, whereby CYP11B2 additionally formed 11β,18-diOH-OT and 11β-OH-OT-18-al, which rearranges to its tautomeric form 11β,18-expoxy-18-OH-OT. CYP11A1 produces six metabolites, which are proposed to include 2-OH-OT, 16-OH-OT, and 2,16-diOH-OT based on liquid chromatography-tandem mass spectrometry analyses. All three enzymes are shown to be inhibited by OT in their natural function. The extent of inhibition thereby depends on the affinity of the enzyme for OT and the strongest effect was demonstrated for CYP11B2. These findings suggest that steroidogenic cytochrome P450 enzymes can contribute to drug metabolism and should be considered in drug design and toxicity studies. Copyright © 2016 by The

  8. Abnormal polyamine metabolism in hereditary muscular dystrophies: effect of human growth hormone.

    Science.gov (United States)

    Rudman, D; Kutner, M H; Chawla, R K; Goldsmith, M A

    1980-01-01

    Previous studies showed hyperre-sponsiveness to human growth hormone (hGH) in men with myotonic or limb girdle dystrophies (MMD or LGD). Because polyamines may mediate some actions of hGH, we have now investigated polyamine metabolism in these and other dystrophies. Under metabolic balance study conditions, serum and urine levels of putrescine (Pu), spermidine (Sd), spermine (Sm), and cadaverine (Cd) were measured in six normal men (36-44 yr), four men with MMD (38-44 yr), and three men with LGD (30-36 yr), before and during treatment with 0.532 U/kg body wt ((3/4)/d) of hGH. Daily balances of N, P, and K were also monitored. In the normal subjects, hGH did not influence elemental balances or serum and urine polyamines. In MMD, hGH caused significant retention of N, P, and K (P muscular dystrophy, age 8-13, did not differ from those in five age-matched normal boys. Skeletal muscle polyamines were measured in five men (31-40 yr) without muscle disease and in three men with LGD (30-38 yr). Average concentrations of Pu, Sd, Sm, and Cd were 46, 306, 548, and 61 nmol/g wet wt in LGD and 1, 121, 245, and 14 in the normal subjects, respectively (P muscular dystrophy and in age- and sex-matched normal controls. Pu, Sd, Sm, and Cd levels were two to three times higher than normal in muscle, but did not differ in liver, kidney, and brain. Similar findings were made in male hamsters with hereditary dystrophy and in their controls. The abnormality in hamster muscle polyamines appeared between 1 and 6 wk of age and persisted or intensified until 30 wk. These data reveal abnormalities of polyamine metabolism in men with MMD, in men with LGD, and in mice or hamsters with hereditary muscular dystrophy. The polyamine disorder could be related to dystrophic patients' hyperresponsiveness to hGH.

  9. Metabolic effects of human growth hormone and of estrogens in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Rudman, D; Chyatte, S B; Patterson, J H; Gerron, G G; O'Beirne, I; Barlow, J; Jordan, A; Shavin, J S

    1972-05-01

    Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)((3/4)) per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested. The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW((3/4)) per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N, P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW((3/4)) per day) produced positive N, P, Na, and K balances in all three Duchenne cases tested with this agent. The data show that exogenous HGH causes a catabolic effect in boys with Duchenne dystrophy. These patients are hyperresponsive to the anabolic effect of diethylstilbestrol. The latter phenomenon may reflect the inhibitory effect of estrogen upon the peripheral actions of these boys' endogenous HGH.

  10. Glutamine and recombinant human growth hormone protect intestinal barrier function following portal hypertension surgery

    Institute of Scientific and Technical Information of China (English)

    Zhao-Feng Tang; Yun-Biao Ling; Nan Lin; Zheng Hao; Rui-Yun Xu

    2007-01-01

    AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery.METHODS: This study was designed as a prospective,randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups: control group (n = 20) and supplemental group (adding Gin and rhGH, n = 22). Every patient received isocaloric and isonitrogenous standard total parenteral nutrition (TPN) starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein (CRP) levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively.RESULTS: On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group (33.7 ± 5.5 vs 31.0± 5.4, P < 0.05, (1.17 ± 0.32 vs 1.05 ± 0.15, P < 0.05,13.94 ± 1.09 vs 12.33±1.33, P < 0.05, and 368.12± 59.25 vs 318.12 ± 45.65, P < 0.05, respectively),whereas the increase in serum TNF-α concentration was significantly reduced (41.02 ± 27.56 vs 160.09 ± 35.17,P < 0.05). The increase in L/M ratio was significantly lower in the supplemental group than in the control group (0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P < 0.05).Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION: Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function,modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.

  11. Bioequivalence studies for three formulations of a recombinant human growth hormone: challenges and lessons learned.

    Science.gov (United States)

    Dao, Le; Jacobs, Joan; Kuebler, Peter; Bakker, Bert; Lippe, Barbara

    2010-10-01

    Two bioequivalence (BE) studies in healthy volunteers comparing new formulations of the recombinant human growth hormone (rhGH) Nutropin AQ (somatropin [rDNA origin] injection; Genentech, Inc., South San Francisco, CA) with the currently marketed formulation (5 mg/mL) were conducted to extend available dosing options. All formulations were administered by subcutaneous (SC) injection ranging in volume from 0.25 to 1.0 mL depending on the formulation concentration. Study A was a 2-period crossover design to assess the BE of 5 and 10 mg/mL. The estimate for relative bioavailability (AUC(0-24 h)) was within the prespecified BE interval (0.80-1.25). However, while the C(max) estimate (1.17) was contained within the range for BE, the 90% CI (0.986-1.38) extended beyond the prespecified BE interval. As a result, Study A failed to show BE between the 5 and 10mg/mL formulations. Review of the data showed unexpected increased variability in the observed C(max). Further review of individual data suggested that in 4 subjects, the GH concentration profile of 1 of the 2 injections closely resembled the absorption kinetics of an intramuscular injection rather than an SC injection. Because study conduct may have contributed to these results, we performed a second study, Study B. This study incorporated injection technique training, a defined injection site, and a larger sample size to accommodate variability. It also included a third formulation, creating a 3-period crossover design to assess the BE of 2.5, 5, and 10 mg/mL. Study B results demonstrated BE of the new 2.5- and 10-mg/mL formulations to the reference 5-mg/mL formulation, and BE to each other, with all 90% CIs within the BE range of 0.80 to 1.25. Thus the challenge of recognizing that design issues could affect outcomes gave us the tools to perform a second study, and the positive results taught us that demonstrating BE is an issue not only of pharmacology, but also of study methodology and execution.

  12. Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli

    Institute of Scientific and Technical Information of China (English)

    Ying Huang; Shu-Ren Wang; Cheng Yi; Ming-Ying Ying; Ying Lin; Mao-Hui Zhi

    2002-01-01

    AIM: To investigate the therapeutic effects of recombinant human growth hormone (rhGH) on rat septic shock with intraabdominal infection by E. coli and its possible mechanism. METHODS: 76 SD rats were divided into 3 groups randomly:control group (group C, n=16) without any special treatnent,of E. coli(1×1010 cfu@ L-1,15 ml@kg-1, ip), treated group (group by rhGH injection (2.25 U@kg-1@d-1, im). Group S and group T were further divided into 1d and 3d subgroups, respectively (n=15 each). Mean arterial pressure (MAP), levels of plasma TNFα and endotoxin and leukocyte count were determined on 1st day and 3rd day after E. coli injection. Another 39 SD rats were divided into groups C, S and T (n=13 each) just for observing survival rate within 1 week.RESULTS: (1) On 1st and 3rd day, MAP in group S decreased markedly, and MAP on 1st day lowered more than that of 3rd day (P<0.01), while MAP in group T just decreased slightly. The survival rate within 1 week was much higher in group T (84.6 %) than in group S (46.2 %) (P<0.01). (2)On 1st day, plasma TNFα and endotoxin elevated significantly in group S and group T (P<0.05), and endotoxin in group S had more increase (P<0.01). On 3rd day, TNFα in group S returned to the level of group C (P>0.05),while TNFα in group T went down below the level of group C(P<0.01). On 3rd day, endotoxin in group S declined, but was still higher than that of group C (P<0.01), endotoxin in group T returned to the level of group C (P>0.05). (3) On 1st day, neutrophil ratio in total leukocyte count in both group S and group T increased significantly (P<0.05 vs group C).CONCLUSION: rhGH showed beneficial effects on rat septic shock. The possible mechanisms may involve the attenuation of bacteria/endotoxin translocation and decreased systemic endotoxin level; inhibition of the production and release of TNFα; improved circulatory function; improved systemic host defenses and maintenance of intestinal mucosa barrier.

  13. Interactions of the human cardiopulmonary, hormonal and body fluid systems in parabolic flight.

    Science.gov (United States)

    Limper, U; Gauger, P; Beck, P; Krainski, F; May, F; Beck, L E J

    2014-06-01

    Commercial parabolic flights accessible to customers with a wide range of health states will become more prevalent in the near future because of a growing private space flight sector. However, parabolic flights present the passengers' cardiovascular system with a combination of stressors, including a moderately hypobaric hypoxic ambient environment (HH) and repeated gravity transitions (GT). Thus, the aim of this study was to identify unique and combined effects of HH and GT on the human cardiovascular, pulmonary and fluid regulation systems. Cardiac index was determined by inert gas rebreathing (CI(rb)), and continuous non-invasive finger blood pressure (FBP) was repeatedly measured in 18 healthy subjects in the standing position while they were in parabolic flight at 0 and 1.8 G(z). Plasma volume (PV) and fluid regulating blood hormones were determined five times over the flight day. Eleven out of the 18 subjects were subjected to an identical test protocol in a hypobaric chamber in ambient conditions comparable to parabolic flight. CI(rb) in 0 G(z) decreased significantly during flight (early, 5.139 ± 1.326 L/min; late, 4.150 ± 1.082 L/min) because of a significant decrease in heart rate (HR) (early, 92 ± 15 min(-1); late, 78 ± 12 min(-1)), even though the stroke volume (SV) remained the same. HH produced a small decrease in the PV, both in the hypobaric chamber and in parabolic flight, indicating a dominating HH effect without a significant effect of GT on PV (-52 ± 34 and -115 ± 32 ml, respectively). Pulmonary tissue volume decreased in the HH conditions because of hypoxic pulmonary vasoconstriction (0.694 ± 0.185 and 0.560 ± 0.207 ml) but increased at 0 and 1.8 G(z) in parabolic flight (0.593 ± 0.181 and 0.885 ± 0.458 ml, respectively), indicating that cardiac output and arterial blood pressure rather than HH are the main factors affecting pulmonary vascular regulation in parabolic flight. HH and GT each lead to specific responses of the

  14. ALX 111: ALX1-11, parathyroid hormone (1-84) - NPS Allelix, PREOS, PTH, recombinant human parathyroid hormone, rhPTH (1-84).

    Science.gov (United States)

    2003-01-01

    ALX 111 [parathyroid hormone (1-84) - NPS Allelix, recombinant human parathyroid hormone, rhPTH (1-84), PREOS] is a full-length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent, such as estrogen or a bisphosphonate. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment, and phase II trials have been completed in Canada and the Netherlands. The 18-month, phase III, multicentre, placebo-controlled trial (Treatment of Osteoporosis with

  15. Challenges in interpretation of thyroid hormone test results

    Directory of Open Access Journals (Sweden)

    Lalić Tijana

    2016-01-01

    Full Text Available Introduction. In interpreting thyroid hormones results it is preferable to think of interference and changes in concentration of their carrier proteins. Outline of Cases. We present two patients with discrepancy between the results of thyroid function tests and clinical status. The first case presents a 62-year-old patient with a nodular goiter and Hashimoto thyroiditis. Thyroid function test showed low thyroid-stimulating hormone (TSH and normal to low fT4. By determining thyroid status (ТSH, T4, fT4, T3, fT3 in two laboratories, basal and after dilution, as well as thyroxine-binding globulin (TBG, it was concluded that the thyroid hormone levels were normal. The results were influenced by heterophile antibodies leading to a false lower TSH level and suspected secondary hypothyroidism. The second case, a 40-year-old patient, was examined and followed because of the variable size thyroid nodule and initially borderline elevated TSH, after which thyroid status showed low level of total thyroid hormones and normal TSH. Based on additional analysis it was concluded that low T4 and T3 were a result of low TBG. It is a hereditary genetic disorder with no clinical significance. Conclusion. Erroneous diagnosis of thyroid disorders and potentially harmful treatment could be avoided by proving the interference or TBG deficiency whenever there is a discrepancy between the thyroid function results and the clinical picture.

  16. Possible participation of calcium in growth hormone release and in thyrotropin-releasing hormone and human pancreatic growth hormone-releasing factor synergy in a primary culture of chicken pituitary cells.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1989-09-01

    We previously reported that thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) exert synergistic (greater than additive) effects on growth hormone (GH) release from chicken pituitary cells in primary culture. In the present studies the possible participation of calcium in GH release and in TRH and hpGRF synergy was investigated. Following dispersion with collagenase, cells were cultured for 48 hr prior to exposure (2 hr) to test agents. Cultured cells were exposed to a range of calcium concentrations (0, 0.02, 0.2, and 2.0 mM) in the presence and absence of secretagogues. These results demonstrated that basal GH release was not altered by the concentration of calcium in the medium: however, secretagogue-induced GH release required calcium. Thus, TRH, hpGRF, 8 Br-cAMP, or forskolin stimulated GH release in the absence of calcium. Furthermore, synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, or forskolin was observed only at the highest calcium concentration (2.0 mM). In other studies, ionomycin (10(-5) M), a calcium ionophore, stimulated GH release to a value about 125% over the basal (absence of test agent) value. Ionomycin-induced GH release was not affected by TRH (5.0 ng/ml); the combined effects of ionomycin (10(-7)-10(-5) M) and hpGRF (5.0 ng/ml) on GH release were less than additive. However, ionomycin (10(-5) M) further increased GH release over that resulting from the synergistic action of TRH and hpGRF (5.0 ng/ml each). Verapamil (a calcium channel blocker) did not affect GH release induced by either TRH or hpGRF (5.0 ng/ml each). However, this agent did inhibit synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, forskolin, or isobutylmethylxanthine. These results suggest that calcium participates in secretagogue-induced GH release from chicken somatotrophs in vitro.

  17. Which follicles make the most anti-Mullerian hormone in humans?

    DEFF Research Database (Denmark)

    Jeppesen, J V; Anderson, R A; Kelsey, T W

    2013-01-01

    Anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells (GC) of the developing pre-antral and antral follicles, and AMH is increasingly used to assess ovarian function. It is unclear which size follicles make the most AMH (total content) and are the main contributors to circulating...

  18. Muscle triacylglycerol and hormone-sensitive lipase activity in untrained and trained human muscles

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Biba, Taus O; Galbo, Henrik

    2006-01-01

    During exercise, triacylglycerol (TG) is recruited in skeletal muscles. We hypothesized that both muscle hormone-sensitive lipase (HSL) activity and TG recruitment would be higher in trained than in untrained subjects in response to prolonged exercise. Healthy male subjects (26 +/- 1 years, body ...

  19. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

    DEFF Research Database (Denmark)

    Nellemann, Birgitte; Vendelbo, Mikkel H; Nielsen, Thomas S

    2014-01-01

    Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

  20. The role of Arg445 and Asp498 in the human thyroid hormone transporter MCT8

    NARCIS (Netherlands)

    S. Groeneweg (Stefan); E.C.H. Friesema (Edith); S. Kersseboom (Simone); W. Klootwijk (Willem); W.E. Visser (Wil Edward); R.P. Peeters (Robin); T.J. Visser (Theo)

    2014-01-01

    textabstractMonocarboxylate transporter 8 (MCT8) facilitates cellular influx and efflux of the thyroid hormones (THs) T4 and T3. Mutations in MCT8 lead to severe psychomotor retardation. Here, we studied the importance of 2 highly conserved residues (Arg445 in transmembrane domain 8 and Asp498 in tr

  1. Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

    DEFF Research Database (Denmark)

    Aslan, Derya; Dahl Andersen, Mille; Gede, Lene Bjerring;

    2012-01-01

    Intermittent low-dose treatment with parathyroid hormone (PTH) analogues has become widely used in the treatment of severe osteoporosis. During normal physiological conditions, PTH stimulates both bone formation and resorption, and in patients with primary hyperparathyroidism, bone loss is frequent...

  2. Oxidative stress biomarkers and hormonal profile in human patients undergoing varicocelectomy.

    Science.gov (United States)

    Hurtado de Catalfo, Graciela E; Ranieri-Casilla, Adalberto; Marra, Fernando A; de Alaniz, María J T; Marra, Carlos A

    2007-12-01

    The aetiology of varicocele is multifactorial although hormonal imbalance and oxidative stress play a key role in the progression of illness. No conclusive evidence has been presented previously, describing the changes in these two factors and the evolution of patients after varicocelectomy. Semen characteristics and hormonal profile were analysed in 36 infertile men with unilateral left varicocele and 33 age-paired controls (proved to be fertile men), after careful inclusion/exclusion selection criteria. Liposoluble and hydrosoluble antioxidants, oligoelements and enzyme activities of the antioxidant defence system were also determined in plasma and erythrocyte from antecubital and spermatic veins, and in spermatozoa. Data were compared between groups at different times before and after varicocelectomy. Decreased levels of liposoluble and hydrosoluble antioxidants and increased activities of the antioxidant defence system enzymes were observed in patients compared with controls. Varicocelectomy normalized this condition at different post-surgical times. Levels of Zn and Se in seminal plasma, protein carbonyls and fragmented DNA remained elevated up to 1 month after surgery. Luteinizing and follicle stimulating hormone concentrations exhibited a biphasic behaviour while testosterone was diminished in patients but normalized soon after varicocelectomy. The results clearly demonstrate the link between the antioxidant defence system, hormonal status and semen characteristics along the post-varicocelectomy period. We suggest that oxidative biomarkers may be appropriate in controlling the evolution of post-varicocelectomy patients, and antioxidant supplementation may improve the clinical condition of infertile men with varicocele.

  3. Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans

    DEFF Research Database (Denmark)

    Lindgren, Ola; Carr, Richard D; Deacon, Carolyn F;

    2011-01-01

    Context: The incretin effect is responsible for the higher insulin response to oral glucose than to iv glucose at matching glucose levels. It is notknownwhetherthis effect is restricted to glucose only. Objective: The aim of the study was to examine whether insulin and incretin hormone responses ...

  4. Health-Related Quality of Life of Young Adults Treated with Recombinant Human Growth Hormone during Childhood.

    Directory of Open Access Journals (Sweden)

    Grit Sommer

    Full Text Available Since recombinant human growth hormone (rhGH became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood.For this study, we retrospectively identified former rhGH patients in 11 centers of paediatric endocrinology, including university hospitals and private practices. We sent a questionnaire to all patients treated with rhGH for any diagnosis, who were older than 18 years, and who resided in Switzerland at time of the survey. Three hundred participants (58% of 514 eligible returned the questionnaire. Mean age was 23 years; 56% were women; 43% had isolated growth hormone deficiency, or idiopathic short stature; 43% had associated diseases or syndromes, and 14% had growth hormone deficiency after childhood cancer. Swiss siblings of childhood cancer survivors and the German norm population served as comparison groups. HRQoL was assessed using the Short Form-36. We found that the Physical Component Summary of healthy patients with isolated growth hormone deficiency or idiopathic short stature resembled that of the control group (53.8 vs. 54.9. Patients with associated diseases or syndromes scored slightly lower (52.5, and former cancer patients scored lowest (42.6. The Mental Component Summary was similar for all groups. Lower Physical Component Summary was associated with lower educational level (coeff. -1.9. Final height was not associated with HRQoL.In conclusion, HRQoL after treatment with rhGH in childhood depended mainly on the underlying indication for rhGH treatment. Patients with isolated growth hormone deficiency/idiopathic short stature or patients with associated diseases or syndromes had HRQoL comparable to peers. Patients with growth hormone deficiency after childhood cancer were

  5. Final Oocyte Maturation in Assisted Reproduction with Human Chorionic Gonadotropin and Gonadotropin-releasing Hormone agonist (Dual Trigger).

    Science.gov (United States)

    Oliveira, Sofia Andrade de; Calsavara, Vinícius Fernando; Cortés, Gemma Castillón

    2016-12-01

    Final oocyte maturation with Human Chorionic Gonadotropin (hCG) and ovarian stimulation with Follicle Stimulation Hormone (FSH) combined with Gonadotrophin-releasing Hormone (GnRH) antagonist to block Luteinizing hormone (LH) surge is a standard procedure of in vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI). However, GnRH agonist has been replacing the use of hCG in certain situations, especially in patients at risk of Ovarian Hyperstimulation Syndrome (OHSS). Some studies have also shown advantages in the combined use of GnRH agonist concurrently with hCG in inducing final oocyte maturation, a treatment known as "Dual Trigger". In theory, this method combines the advantages of both induction regimens, and it has brought promising results. The objective of this study is to compare Dual Trigger with the use of hCG alone or the use of GnRH agonist alone. A systematic review of articles on Dual Trigger and a retrospective cohort study comparing the three methods of induction of final oocyte maturation have been conducted. It has been found that Dual Triggering for poor responder patients had a statistically significant increase in the number of retrieved oocytes, mature oocytes, and fertilized embryos in the positive beta hCG rate, implantation rate, and newborn/transferred embryo (TE) rate.

  6. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor–positive human breast cancer

    Science.gov (United States)

    Miller, Todd W.; Hennessy, Bryan T.; González-Angulo, Ana M.; Fox, Emily M.; Mills, Gordon B.; Chen, Heidi; Higham, Catherine; García-Echeverría, Carlos; Shyr, Yu; Arteaga, Carlos L.

    2010-01-01

    Many breast cancers exhibit a degree of dependence on estrogen for tumor growth. Although several therapies have been developed to treat individuals with estrogen-dependent breast cancers, some tumors show de novo or acquired resistance, rendering them particularly elusive to current therapeutic strategies. Understanding the mechanisms by which these cancers develop resistance would enable the development of new and effective therapeutics. In order to determine mechanisms of escape from hormone dependence in estrogen receptor–positive (ER-positive) breast cancer, we established 4 human breast cancer cell lines after long-term estrogen deprivation (LTED). LTED cells showed variable changes in ER levels and sensitivity to 17β-estradiol. Proteomic profiling of LTED cells revealed increased phosphorylation of the mammalian target of rapamycin (mTOR) substrates p70S6 kinase and p85S6 kinase as well as the PI3K substrate AKT. Inhibition of PI3K and mTOR induced LTED cell apoptosis and prevented the emergence of hormone-independent cells. Using reverse-phase protein microarrays, we identified a breast tumor protein signature of PI3K pathway activation that predicted poor outcome after adjuvant endocrine therapy in patients. Our data suggest that upon adaptation to hormone deprivation, breast cancer cells rely heavily on PI3K signaling. Our findings also imply that acquired resistance to endocrine therapy in breast cancer may be abrogated by combination therapies targeting both ER and PI3K pathways. PMID:20530877

  7. Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings

    Directory of Open Access Journals (Sweden)

    Rushika Conroy

    2014-01-01

    Full Text Available Bariatric surgery improves glucose homeostasis and alters gut hormones partly independent of weight loss. Leptin plays a role in these processes; levels are decreased following bariatric surgery, creating a relative leptin insufficiency. We previously showed that leptin administration in a weight-reduced state after Roux-en-Y gastric bypass (RYGB caused no further weight loss. Here, we discuss the impact of leptin administration on gut hormones, glucostasis, and appetite. Weight stable women after RYGB were randomized to receive placebo or recombinant human metreleptin (0.05 mg/kg twice daily. At weeks 0 and 16, a liquid meal challenge was performed. Glucose, insulin, C-peptide, GLP-1, PYY, glucagon, and ghrelin (total, acyl, and desacyl were measured fasting and postprandially. Appetite was assessed using a visual analog scale. Mean post-op period was 53±2.3 months; mean BMI was 34.6±0.2 kg/m2. At 16 weeks, there was no significant change in weight within or between groups. Fasting PYY was significantly different between groups and the leptin group had lower sweets craving at week 16 than the placebo group (P<0.05. No other differences were observed. Leptin replacement does not alter gut hormones or glucostasis but may diminish sweet cravings compared to placebo in this population of post-RYGB women.

  8. Hormonal and Dietary Characteristics in Obese Human Subjects with and without Food Addiction

    Directory of Open Access Journals (Sweden)

    Pardis Pedram

    2014-12-01

    Full Text Available The concept of food addiction (FA is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight, the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat and the percent calorie intake from fat and carbohydrates (g/kg was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium, fat and its components (such as saturated, monounsaturated and trans fat, omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.

  9. Hormonal and dietary characteristics in obese human subjects with and without food addiction.

    Science.gov (United States)

    Pedram, Pardis; Sun, Guang

    2014-12-31

    The concept of food addiction (FA) is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO) matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight), the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat) and the percent calorie intake from fat and carbohydrates (g/kg) was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium), fat and its components (such as saturated, monounsaturated and trans fat), omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity.

  10. Crosstalk between integrin αvβ3 and estrogen receptor-α is involved in thyroid hormone-induced proliferation in human lung carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Ran Meng

    Full Text Available A cell surface receptor for thyroid hormone that activates extracellular regulated kinase (ERK 1/2 has been identified on integrin αvβ3. We have examined the actions of thyroid hormone initiated at the integrin on human NCI-H522 non-small cell lung carcinoma and NCI-H510A small cell lung cancer cells. At a physiologic total hormone concentration (10(-7 M, T(4 significantly increased proliferating cell nuclear antigen (PCNA abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T(3 at a supraphysiologic concentration. Neutralizing antibody to integrin αvβ3 and an integrin-binding Arg-Gly-Asp (RGD peptide blocked thyroid hormone-induced PCNA expression. Tetraiodothyroacetic acid (tetrac lacks thyroid hormone function but inhibits binding of T(4 and T(3 to the integrin receptor; tetrac eliminated thyroid hormone-induced lung cancer cell proliferation and ERK1/2 activation. In these estrogen receptor-α (ERα-positive lung cancer cells, thyroid hormone (T(4>T(3 caused phosphorylation of ERα; the specific ERα antagonist ICI 182,780 blocked T(4-induced, but not T(3-induced ERK1/2 activation, as well as ERα phosphorylation, proliferating-cell nuclear antigen (PCNA expression and hormone-dependent thymidine uptake by tumor cells. Thus, in ERα-positive human lung cancer cells, the proliferative action of thyroid hormone initiated at the plasma membrane is at least in part mediated by ERα. In summary, thyroid hormone may be one of several endogenous factors capable of supporting proliferation of lung cancer cells. Activity as an inhibitor of lung cancer cell proliferation induced at the integrin receptor makes tetrac a novel anti-proliferative agent.

  11. Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6) developed for controlled ovarian stimulation prior to assisted...... reproductive technologies. Methods: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed...... effects population pharmacokinetic modelling in NONMEM 7.2.0. Results: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent...

  12. Metabolic and Behavioural Phenotypes in Nestin-Cre Mice Are Caused by Hypothalamic Expression of Human Growth Hormone.

    Directory of Open Access Journals (Sweden)

    Jeroen Declercq

    Full Text Available The Nestin-Cre driver mouse line has mild hypopituitarism, reduced body weight, a metabolic phenotype and reduced anxiety. Although several causes have been suggested, a comprehensive explanation is still lacking. In this study we examined the molecular mechanisms leading to this compound phenotype. Upon generation of the Nestin-Cre mice, the human growth hormone (hGH minigene was inserted downstream of the Cre recombinase to ensure efficient transgene expression. As a result, hGH is expressed in the hypothalamus. This results in the auto/paracrine activation of the GH receptor as demonstrated by the increased phosphorylation of signal transducer and activator of transcription 5 (STAT5 and reduced expression of growth hormone releasing hormone (Ghrh. Low Ghrh levels cause hypopituitarism consistent with the observed mouse growth hormone (mGH deficiency. mGH deficiency caused reduced activation of the GH receptor and hence reduced phosphorylation of STAT5 in the liver. This led to decreased levels of hepatic Igf-1 mRNA and consequently postnatal growth retardation. Furthermore, genes involved in lipid uptake and synthesis, such as CD36 and very low-density lipoprotein receptor were upregulated, resulting in liver steatosis. In conclusion, this study demonstrates the unexpected expression of hGH in the hypothalamus of Nestin-Cre mice which is able to activate both the GH receptor and the prolactin receptor. Increased hypothalamic GH receptor signaling explains the observed hypopituitarism, reduced growth and metabolic phenotype of Nestin-Cre mice. Activation of either receptor is consistent with reduced anxiety.

  13. {sup 18F} FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Seung Hwan; Eo, Jae Sun; Lee, Jong Jin; Chung, June Key; Lee, Dong Soo; Lee, Myung Chul [Seoul National Univ. Hospital, Seoul (Korea, Republic of)

    2011-12-15

    The purpose of this study was to evaluate glucose metabolism of normal human testis on {sup 18F} FDG PET/CT and to assess possible correlation among age, the serum levels of sex hormones, and vasectomy. {sup 18F} FDG PET/CT was performed in 66 normal healthy men (50.8{+-}13.6 years, range 22-81), and mean standard uptake values (SUV) of {sup 18F} FDG in testis and adductor muscle were measured. Testis muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. {sup 18F} FDG PET/CT was also performed in 32 vasectomized men (55.7{+-}7.8 years, range 38-71) and 52 nonvasectomized men (55.4{+-}11.6 years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age related decline was found in T/M ratio (r=-0.509, p<0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r=-0.427, p=0.0003; r=0.435, p=0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p<0.0378 and p=0.0001, respectively). Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular {sup 18F} FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular {sup 18F} FDG uptake in the normal adult population.

  14. Lichen planus-like drug reaction associated with recombinant human growth hormone therapy in a child patient with Turner syndrome.

    Science.gov (United States)

    Soares, Mariana Quirino Silveira; Mendonca, Elismauro Fancisco

    2016-01-01

    Turner syndrome (TS) is a genetic disease with an incidence rate of between 1:2000 and 1:5000 live female births. The treatment of TS differs according to age and Recombinant Human Growth Hormone (RHGH) therapy is usually given for the treatment of short stature in girls with TS in childhood. We describe the first case of a TS patient who presented with a clinical picture compatible with oral and palmoplantar lichen planus-like reaction during RHGH therapy; spontaneous remission occurred after therapy suspension.

  15. Direct and label-free detection of the human growth hormone in urine by an ultrasensitive bimodal waveguide biosensor.

    Science.gov (United States)

    González-Guerrero, Ana Belén; Maldonado, Jesús; Dante, Stefania; Grajales, Daniel; Lechuga, Laura M

    2017-01-01

    A label-free interferometric transducer showing a theoretical detection limit for homogeneous sensing of 5 × 10(-8) RIU, being equivalent to a protein mass coverage resolution of 2.8 fg mm(-2) , is used to develop a high sensitive biosensor for protein detection. The extreme sensitivity of this transducer combined with a selective bioreceptor layer enables the direct evaluation of the human growth hormone (hGH) in undiluted urine matrix in the 10 pg mL(-1) range.

  16. Interleukin-8 production from human somatotroph adenoma cells is stimulated by interleukin-1β and inhibited by growth hormone releasing hormone and somatostatin

    DEFF Research Database (Denmark)

    Vindeløv, Signe Diness; Hartoft-Nielsen, Marie-Louise; Rasmussen, Åse Krogh;

    2011-01-01

    Pituitary adenomas cause morbidity and mortality due to their localization and influence on pituitary hormone secretion. Although the pathogenesis of pituitary adenomas is unclear, studies have indicated that cytokines are involved. We investigated the role of cytokines, in particular interleukin...... (IL)-8, in the pathogenesis of growth hormone (GH) producing tumours.......Pituitary adenomas cause morbidity and mortality due to their localization and influence on pituitary hormone secretion. Although the pathogenesis of pituitary adenomas is unclear, studies have indicated that cytokines are involved. We investigated the role of cytokines, in particular interleukin...

  17. Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone.

    Science.gov (United States)

    Irwin, David J; Abrams, Joseph Y; Schonberger, Lawrence B; Leschek, Ellen Werber; Mills, James L; Lee, Virginia M-Y; Trojanowski, John Q

    2013-04-01

    Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)-associated proteins (NDAPs) (ie, tau, Aβ, and α-synuclein) suggests possible similarities to the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of ND