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Sample records for releasing hormone therapy

  1. Preliminary studies of plasma growth hormone releasing activity during medical therapy of acromegaly

    International Nuclear Information System (INIS)

    Hagen, T.C.; Lawrence, A.M.; Kirsteins, L.

    1978-01-01

    The in vitro growth hormone releasing activity of plasma obtained from six acromegalic subjects was measured before and during therapy. In five subjects, plasmas were obtained before and during successful medical therapy with medroxyprogesterone acetate (MPA). The sixth subject was sampled before and after transphenoidal Sr 90 -induced hypopituitarism. All subjects had a decrement in fasting growth hormone levels with respective therapies (29-88%). The in vitro growth hormone released from Rhesus monkey anterior pituitaries was assessed after incubating one lateral half in control plasma (pre-therapy) and the contralateral pituitary half in plasma obtained during or after therapy. Studies with plasmas obtained from the five patients successfully treated with MPA showed a decrease in growth hormone releasing activity during therapy in all (18-57%). Plasma obtained after Sr 90 pituitary ablation in the sixth subject had 35% more growth hormone releasing activity than obtained before therapy. These results suggest that active acromegalics who respond to MPA with significantly lowered growth hormone levels may actually achieve this response because of a decrease in growth hormone releasing factor measured peripherally. The opposite response in one acromegalic subject, following Sr 90 pituitary ablation and hypopituitarism, suggests that growth hormone releasing factor secretion may increase when growth hormone levels are lowered by ablative therapy. (orig.) [de

  2. Lower testosterone levels with luteinizing hormone-releasing hormone agonist therapy than with surgical castration: new insights attained by mass spectrometry

    NARCIS (Netherlands)

    van der Sluis, Tim M.; Bui, Hong N.; Meuleman, Eric J. H.; Heijboer, Annemieke C.; Hartman, Jeroen F.; van Adrichem, Nick; Boevé, Egbert; de Ronde, Willem; van Moorselaar, R. Jeroen A.; Vis, André N.

    2012-01-01

    Androgen deprivation therapy by bilateral orchiectomy (surgical castration) or luteinizing hormone-releasing hormone agonist therapy (medical castration) is recommended for advanced or metastatic prostate cancer. Both methods aim at reducing serum testosterone concentrations to a castrate level

  3. Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing Hormone-Releasing Hormone Agonist Therapy.

    Science.gov (United States)

    Morote, Juan; Comas, Inma; Planas, Jacques; Maldonado, Xavier; Celma, Ana; Placer, José; Ferrer, Roser; Carles, Joan; Regis, Lucas

    2018-04-01

    Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation therapy (ADT) and to diagnose castration resistance in patients with prostate cancer (PCa). Currently, the accepted castrate level of serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass spectrometry (LC MSMS) is the appropriate method to measure testosterone, especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are used in clinical laboratories, despite their lack of accuracy and reproducibility, because they are automatable, fast, sensitive, and inexpensive. We compared serum testosterone levels measured using LC MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing hormone (LHRH) agonist therapy. The median serum testosterone level was 14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6 ng/dL) with CLIA (P  50 ng/dL in 3 patients (2.4%). These ranges were found in 34 (27%), 72 (57.1%), and 20 (15.9%) patients when testosterone was measured using CLIA (P < .001). The castrate level of serum testosterone using LC MSMS and CLIA was 39.8 ng/dL (95% confidence interval [CI], 37.1-43.4 ng/dL) and 66.5 ng/dL (95% CI, 62.3-71.2 ng/dL), respectively. We found that CLIA overestimated the testosterone levels in PCa patients undergoing LHRH agonist therapy. Thus, the castration level was incorrectly considered inadequate with CLIA in almost 15% of patients. The true castration level of serum testosterone using an appropriate method is < 50 ng/dL. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Hormone Therapy

    Science.gov (United States)

    ... it also can be a sign of endometrial cancer. All bleeding after menopause should be evaluated. Other side effects reported by women who take hormone therapy include fluid retention and breast soreness. This soreness usually lasts for a short ...

  5. Effects of growth hormone deficiency and recombinant growth hormone therapy on postprandial gallbladder motility and cholecystokinin release.

    NARCIS (Netherlands)

    Moschetta, A.; Twickler, M.; Rehfeld, J.F.; Ooteghem, N.A. van; Castro Cabezas, M.; Portincasa, P.; Berge-Henegouwen, G.P. van; Erpecum, K.J. van

    2004-01-01

    In addition to cholecystokinin, other hormones have been suggested to be involved in regulation of postprandial gallbladder contraction. We aimed to evaluate effects of growth hormone (GH) on gallbladder contractility and cholecystokinin release. Gallbladder and gastric emptying (by ultrasound) and

  6. Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

    Directory of Open Access Journals (Sweden)

    Alun L Edwards

    1996-01-01

    Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

  7. Menstruation recovery after chemotherapy and luteinizing hormone-releasing hormone agonist plus tamoxifen therapy for premenopausal patients with breast cancer.

    Science.gov (United States)

    Sakurai, Kenichi; Matsuo, Sadanori; Enomoto, Katsuhisa; Amano, Sadao; Shiono, Motomi

    2011-01-01

    Little is known about the period required for menstruation recovery after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen therapy following chemotherapy. In this study we investigated the period required for menstruation recovery after the therapy. The subjects comprised 105 premenopausal breast cancer patients who had undergone surgery. All patients were administered an LH-RH agonist for 24 months and tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the status of menstruation recovery was examined. Menstruation resumed in 16 cases (15.2%) after the last LH-RH agonist treatment session. The mean period from the last LH-RH agonist treatment to the recovery of menstruation was 6.9 months. The rate of menstruation recovery was 35.5% in patients aged 40 years or younger and 8.0% in those aged 41 years or older, and it was significantly higher in those aged 40 years or younger. The period until menstruation recovery tended to be longer in older patients at the end of treatment. This study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.

  8. Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

    Science.gov (United States)

    Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

    2006-06-01

    Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

  9. Does Gonadotropin Releasing Hormone Agonists plus add-back therapy bring an aurora to orthodontic treatment?

    Directory of Open Access Journals (Sweden)

    Jiang Lingyong

    2012-01-01

    Full Text Available Introduction: Obviously, long therapy time of orthodontic treatment and a number of its adverse effects, such as pain, root resorption, enamel demineralization, periodontal disease, are the main reasons of complaints from patients. It is the first thing for an orthodontist to shorten the period of treatment and decrease the complications of orthodontic treatment as much as possible. The Hypothesis: We hypothesis Gonadotropin Releasing Hormone Agonists (GnRHa and add-back therapy can create the "therapeutic window", namely, the appropriate estrogen level and assuage the adverse effects of estrogen deficiency which should be avoided as much as possible. Evaluation of the Hypothesis: It is generally acknowledged that estrogen has direct regulating role in bone metabolism by acting on osteoblasts and osteoclasts. Estrogen deficiency can increase the rate of orthodontic tooth movement and also bring about some adverse effects. The appropriate estrogen level, which we call the "therapeutic window" in orthodontic treatment, can speed up the orthodontic tooth movement and eliminate the adverse effects as far as possible. GnRHa can be the maker of estrogen deficiency; meanwhile, add-back therapy can remove the adverse effects by estrogen deficiency. So, we believe that GnRHa plus add-back therapy could be a new adjuvant method of orthodontic treatment and be good for orthodontists and patients.

  10. [Spermatogenesis of pulsatile gonadotropin-releasing hormone infusion versus gonadotropin therapy in male idiopathic hypogonadotropic hypogonadism].

    Science.gov (United States)

    Huang, Bingkun; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Liu, Zhaoxiang; Nie, Min; Wu, Xueyan

    2015-05-26

    To compare the efficacies of pulsatile gonadotropin-releasing hormone (GnRH) versus human chorionic gonadotropin/human menopausal gonadotropin (HCG/HMG) for spermatogenesis in male idiopathic hypogonadotropic hypogonadism (IHH). For this retrospective study, a total of 92 male IHH outpatients from May 2010 to October 2014 were recruited and categorized into GnRH (n = 40) and HCG/HMG (n = 52) groups. Each subject selected one specific therapy voluntarily. The gonadotropin levels were measured in the first week and monthly post-treatment in GnRH group. And serum total testosterone (TT), testicular volume (TV) and rate of spermatogenesis were observed monthly post-treatment in two groups. Spermatogenesis, TT and TV were compared between two groups. All IHH patients were treated for over 3 months. The median follow-up periods in GnRH and HCG/HMG groups was 8.2 (3.0-18.4) and 9.2 (3.0-18.6) months respectively (P = 0.413). In GnRH group, LH ((0.5 ± 0.6) vs (3.4 ± 2.4) U/L, P treatment. In GnRH group, at the end of follow-up, TT ((1.0 ± 1.0) vs (7.4 ± 5.2) nmol/L, P treatment time for initial sperm appearance than HCG/HMG group ((6.5 ± 3.1) vs (10.8 ± 3.7) months, P = 0.001). Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

  11. Variations of serum testosterone levels in prostate cancer patients under LH-releasing hormone therapy: an open question.

    Science.gov (United States)

    Reis, Leonardo Oliveira

    2012-06-01

    The hypothesis 'the lower the better when achieving castration levels of testosterone' is based on the data from second-line hormonal manipulation and its molecular basis, and on better oncological results reported for lower castration levels in prostate cancer (PCa) patients, including those achieved with maximal androgen blockade. In this regard, the equivalence of surgical and different pharmacological castrations has been controversial. The modified amino acid structure that makes LH-releasing hormone (LHRH) analogs more potent than LHRH, and the method of delivering the analogs impacts on bioavailibility and potentially causes differences in androgen levels and in its final oncological efficacy. In addition to this, there is a myriad of circumstances, such as those related to ethnic variations and co-morbidities, which uniquely impact on the pharmacological approach in a highly heterogeneous population of castration-resistant prostate cancer (CRPC) patients. Ineffective testosterone suppression through hormonal escape is currently poorly recognized and may result in increased PCa mortality. Until now, the optimal serum testosterone level in patients under castration, and the impact of its variations in patients under LHRH therapy, remain open questions and have been merged to a broad spectra of patients who are highly heterogeneous. This heterogeneity relates to a number of mechanisms regarding response to treatment, which influences the biology of the relapsing tumor and the sensitivity to subsequent therapies in the individual patient. The rationale to achieve testosterone levels below 20-50 ng/dl warrant further investigation as these levels have recently rescued CRPC patients. In the last few years and months, important advancements in prostate cancer treatment have been achieved. Nevertheless, these advances are measured in a few months of additional survival and under high costs, not available to most of the world population, compared with the benefits

  12. Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

    Science.gov (United States)

    Shen, Z Q; Xu, J J; Lin, J F

    2013-11-01

    Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 μg GnRH challenge was tested every three months. Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

  13. Growth Hormone-Releasing Hormone in Diabetes

    Directory of Open Access Journals (Sweden)

    Leonid Evsey Fridlyand

    2016-10-01

    Full Text Available Growth hormone-releasing hormone (GHRH is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR has been demonstrated in different peripheral tissues and cell types including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of Type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggesting that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.

  14. Pulsatile gonadotropin-releasing hormone therapy is associated with earlier spermatogenesis compared to combined gonadotropin therapy in patients with congenital hypogonadotropic hypogonadism

    Directory of Open Access Journals (Sweden)

    Jiang-Feng Mao

    2017-01-01

    Full Text Available Both pulsatile gonadotropin-releasing hormone (GnRH infusion and combined gonadotropin therapy (human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG] are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism (CHH. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH: twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months (range: 12-27 months for the GnRH group and 28.7 ± 13.0 months (range: 12-66 months for the HCG/HMG group. The median time to first sperm appearance was 6 months (95% confidence interval [CI]: 1.6-10.4 in the GnRH group versus 18 months (95% CI: 16.4-20.0 in the HCG/HMG group (P 1 × 10 6 ml−1 was 43.7% ± 20.4% (16 samples in the GnRH group versus 43.2% ± 18.1% (153 samples in the HCG/HMG group (P = 0.921. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group (8.3 ± 4.6 vs 16.2 ± 8.2 nmol l−1 , P < 0.001. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.

  15. Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia.

    Science.gov (United States)

    Quintos, J B; Vogiatzi, M G; Harbison, M D; New, M I

    2001-04-01

    Short stature in the adult patient with congenital adrenal hyperplasia (CAH) is commonly seen, even among patients in excellent adrenal control during childhood and puberty. In this study we examine the effect of GH therapy on height prediction in children with both CAH and compromised height prediction. Leuprolide acetate, a GnRH analog (GnRHa), was given to patients with evidence of early puberty. GH (n = 12) or the combination of GH and GnRHa (n = 8) was administered to 20 patients with CAH while they continued therapy with glucocorticoids. Each patient in the treatment group was matched according to age, sex, bone age, puberty, and type of CAH with another CAH patient treated only with glucocorticoid replacement. The match was made at the start of GH treatment. Of the 20 patients, 12 have completed 2 yr of therapy. After 1 yr of GH or combination GH and GnRHa therapy, the mean growth rate increased from 5 +/- 1.9 to 7.8 +/- 1.6 cm/yr vs. 5.4 +/- 1.7 to 5 +/- 2 cm/yr in the group not receiving GH (P growth rate was 6 +/- 1.6 vs. 4.2 +/- 2.1 cm/yr in the group not receiving GH (P growth rate and height prediction and a reduction in height deficit for bone age.

  16. New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

    Science.gov (United States)

    Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

    1992-10-01

    The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

  17. Growth hormone-releasing peptides.

    Science.gov (United States)

    Ghigo, E; Arvat, E; Muccioli, G; Camanni, F

    1997-05-01

    Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration: in fact, prolonged administration of GHRPs increases IGF-1 levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and

  18. Hormone Replacement Therapy and Your Heart

    Science.gov (United States)

    Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal ...

  19. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  20. Radioimmunological and clinical studies with luteinizing hormone releasing hormone (LRH)

    International Nuclear Information System (INIS)

    Dahlen, H.G.

    1986-01-01

    Radioimmunoassay for Luteinizing Hormone Releasing Hormone (LRH) has been established, tested and applied. Optimal conditions for the performance with regards to incubation time, incubation temperature, concentration of antiserum and radiolabelled LRH have been established. The specificity of the LRH immunoassay was investigated. Problems with direct measurement of LRH in plasmas of radioimmunoassay are encountered. The LRH distribution in various tissues of the rat are investigated. By means of a system for continuous monitoring of LH and FSH in women the lowest effective dose of LRH causing a significant release of LH and FSH could be established. (Auth.)

  1. Thyroid hormone replacement therapy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

  2. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  3. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  4. Patient communication in hormone therapy.

    Science.gov (United States)

    Schnare, S M

    2001-01-01

    Common regimens of HRT therapy are reviewed, including common routes of hormone administration. Inconsistent patterns of HRT use are discussed, including the reasons women most often give for discontinuing hormone therapies. Specific issues related to misperceptions and fears regarding HRT are clarified, and specific, focused patient education formats are discussed to address women's common concerns about HRT. Obstacles to HRT use are elucidated, with suggestions for clinicians about how to communicate more effectively with women: clinicians must focus on emotional and physical aspects of HRT choices and tailor therapies to the individual patient. Discussing frankly the very serious concerns of women regarding the association between lobular breast cancer and endometrial cancer is important; discussing and preparing women for possible side effects helps patients cope better if and when side effects occur. Finally, offering a wide variety of HRT therapies provides women with a broader choice if an initial regimen is unsuccessful.

  5. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  6. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    International Nuclear Information System (INIS)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

    1989-01-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

  7. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

    Science.gov (United States)

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  8. Effects of hyperthyroidism and hypothyroidism on rat growth hormone release induced by thyrotropin-releasing hormone.

    Science.gov (United States)

    Chihara, K; Kato, Y; Ohgo, S; Iwasaki, Y; Maeda, K

    1976-06-01

    The effect of synthetic thyrotropin-releasing hormone (TRH) on the release of growth hormone (GH) and thyroid-stimulating hormone (TSH) was investigated in euthyroid, hypothyroid, and hyperthyroid rats under urethane anesthesia. In euthyroid control rats, intravenous injection of TRH (200 ng/100 g BW) resulted in a significant increase in both plasma GH and TSH. In rats made hypothyroid by treatment with propylthiouracil or by thyroidectomy, basal GH and TSH levels were significantly elevated with exaggerated responses to TRH. In contrast, plasma GH and TSH responses to TRH were both significantly inhibited in rats made hyperthyroid by L-thyroxine (T4) treatment. These results suggest that altered thyroid status influences GH release as well as TSH secretion induced by TRH in rats.

  9. The role of releasing hormones in the diagnosis of hypopituitarism ...

    African Journals Online (AJOL)

    Luteinising hormone-releasing factor and thyrotrophinreleasing factor were used in conjunction with the insulin tolerance test in 9 patients with known or suspected panhypopituitarism. It appears that growth hormone and luteinising hormone fail early in panhypopituitarism. Cortisol and thyroid-stimulating hormone ...

  10. Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

    Science.gov (United States)

    Harvey, S; Gineste, C; Gaylinn, B D

    2014-08-01

    Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Potent agonists of growth hormone-releasing hormone. Part I.

    Science.gov (United States)

    Zarandi, M; Serfozo, P; Zsigo, J; Bokser, L; Janaky, T; Olsen, D B; Bajusz, S; Schally, A V

    1992-03-01

    Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D-Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro, respectively. These two peptides contained Met27. Their Nle27 analogs, [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D-Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of 10.5 and 2.4, respectively. These data indicate that replacement of Met27 by Nle27 enhanced the GH-releasing activity of the analog when the molecule contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D-Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2-51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149), possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

    Science.gov (United States)

    Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

    1992-02-01

    In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

  13. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

    Ravn, S H; Rosenberg, J; Bostofte, E

    1994-01-01

    The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy....... This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes...... in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin...

  14. Hormone Replacement Therapy: MedlinePlus Health Topic

    Science.gov (United States)

    ... of hormone therapy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hormone Replacement Therapy ... Estrogen overdose Types of hormone therapy Related Health Topics Menopause National Institutes of Health The primary NIH ...

  15. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke

    2013-01-01

    To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

  16. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. ...

  17. Effects of hormone therapy on blood pressure.

    Science.gov (United States)

    Issa, Zeinab; Seely, Ellen W; Rahme, Maya; El-Hajj Fuleihan, Ghada

    2015-04-01

    Although hormone therapy remains the most efficacious option for the management of vasomotor symptoms of menopause, its effects on blood pressure remain unclear. This review scrutinizes evidence of the mechanisms of action of hormone therapy on signaling pathways affecting blood pressure and evidence from clinical studies. Comprehensive Ovid MEDLINE searches were conducted for the terms "hypertension" and either of the following "hormone therapy and menopause" or "selective estrogen receptor modulator" from year 2000 to November 2013. In vitro and physiologic studies did not reveal a clear deleterious effect of hormone therapy on blood pressure. The effect of oral therapy was essentially neutral in large trials conducted in normotensive women with blood pressure as primary outcome. Results from all other trials had several limitations. Oral therapy had a neutral effect on blood pressure in hypertensive women. Transdermal estrogen and micronized progesterone had a beneficial effect on blood pressure in normotensive women and, at most, a neutral effect on hypertensive women. In general, tibolone and raloxifene had a neutral effect on blood pressure in both hypertensive and normotensive women. Large randomized trials are needed to assess the effect of oral hormone therapy on blood pressure as a primary outcome in hypertensive women and the effect of transdermal preparations on both normotensive and hypertensive women. Transdermal preparations would be the preferred mode of therapy for hypertensive women, in view of their favorable physiologic and clinical profiles. The decision regarding the use of hormone therapy should be individualized, and blood pressure should be monitored during the course of treatment.

  18. Radioimmunoassay for luteinizing hormone releasing hormone in plasma

    International Nuclear Information System (INIS)

    Saito, Shiro; Musa, Kimitaka; Oshima, Ichiyo; Yamamoto, Suzuyo; Funato, Toyohiko

    1975-01-01

    A sensitive and specific double antibody radioimmunoassay has been developed capable of measuring LH-RH in extracted human plasma. Thyrotropin releasing hormone, lysine vasopressin and most of LH-RH analogues did not appear to affect the assay. Hypothalamic extract and some of the LH-RH analogues produced displacement curves which were parallel to the curve obtained with the synthetic LH-RH. Sensitivity of the radioimmunoassay was about 3 pg per assay tube. The coefficient of variation of intraassays was 6.4%, while that of interassays was 9.6%. Exogenous LH-RH could be quantitatively extracted by acidic ethanol when varying amounts of synthetic LH-RH were added to the plasma. Immunoreactivity of LH-RH was preserved in plasma for 2 hrs in the cold but was gradually reduced thereafter. The plasma levels of LH-RH were 20 pg/ml or less in normal adults and not detectable in children. Aged males over 60 yr and postmenopausal women showed a tendency to have higher levels of plasma LH-RH. The plasma LH-RH level was significantly higher in midcycle than in the follicular or luteal stages. The disappearance rate of LH-RH from the circulation after intravenous injection could be represented as half-times of 4-6 min. Between 0.2-0.4% of the injected dose was excreted into urine within 1 hr. These results indicate that the determination of LH-RH might be a useful tool for elucidating hypothalamic-pituitary-gonad interactions. (auth.)

  19. Hormone Therapy and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Fang-Ping Chen

    2006-12-01

    Full Text Available As in other Western countries, cardiovascular disease (CVD is the leading cause of death among women in Taiwan, exceeding the mortality from cervical or breast cancer. Women generally present with CVD after menopause and later than men, since menopause-related estrogen deficiency has been considered to be associated with an increased risk for CVD. Thus, coronary artery diseases and stroke are the two main contributors of mortality among postmenopausal women. Observational studies have reported a reduction in coronary artery disease risk after hormone therapy (HT ranging from 31-44%. However, recent randomized controlled trials that evaluated the effect of HT on primary and secondary CVD prevention have questioned the efficacy of HT, despite confirming the lipid-lowering effect of estrogen. However, a cluster of factors are responsible for the genesis and progression of CVD. Until we further evaluate their specific actions and how these different factors interact, the issue related to HT and cardiovascular risk will remain unsettled. Since these studies have contributed to our understanding of the benefits and risks associated with HT, HT use should be individualized after consideration of the condition of each postmenopausal patient. Ideally, the efficacy of different preparations and dosages of HT in postmenopausal women who are at risk of CVD, before atheromatous lesions have developed, should be investigated.

  20. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...

  1. Therapy for obesity based on gastrointestinal hormones

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Christensen, Mikkel; Knop, Filip K

    2011-01-01

    It has long been known that peptide hormones from the gastrointestinal tract have significant impact on the regulation of nutrient metabolism. Among these hormones, incretins have been found to increase insulin secretion, and thus incretin-based therapies have emerged as new modalities...

  2. Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease.

    Science.gov (United States)

    Taskin, O; Yalcinoglu, A I; Kafkasli, A; Burak, F; Ozekici, U

    1996-06-01

    To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD). Prospective, randomized. University-based infertility clinic. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.

  3. contribution of growth hormone-releasing hormone and

    African Journals Online (AJOL)

    The strategy used was to stimulate GH secretion in 8 young ... treatment with two oral doses of 50 mg atenolol (to inhibit .... had normal baseline thyroid-stimulating hormone (TSH) ..... production rate of 14% per decade has been documented.'".

  4. Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1990-01-01

    It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic...

  5. Menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Ali Baziad

    2001-12-01

    Full Text Available The global population in the 21st century has reached 6.2 billion people, by the year 2025 it is to be around 8.3-8.5 billion, and will increase further. Elderly people are expected to grow rapidly than other groups. The fastest increase in the elderly population will take place in Asia. Life expectancy is increasing steadily throughout developed and developing countries. For many  menopausal women, increased life expectancy will accompanied by many health problems. The consequences of estrogen deficiency are the menopausal symptoms. The treatment of menopause related complaints and diseases became an  important socioeconomic and medical issue. Long term symptoms, such as the increase in osteoporosis fractures, cardio and cerebrovascular disesses and dementia, created a large financial burden on individuals and society. All these health problems can be lreated or prevented by hormone replacement therapy (HRT. Natural HRT is usually prefened. Synthetic  estrogen in oral contraceptives (oc are not recommended for HRT. Many contra-indications for oc, but now it is widely usedfor HRT. The main reasons for discontinuing HRT are unwanted bleeding, fear of cancer, and negative side effects. Until now there are sill debates about the rebrtonship between HRT and the incidence of breast cancer. Many data showed that there were no clear relationship between the use of HRT and breast cancer. ThereÎore, nwny experts advocate the use of HRTfrom the first sign of climacteric complaints until death. (Med J Indones 2001;10: 242-51Keywords: estrogen deficiency, climacteric phases, tibolone.

  6. Growth hormone therapy: emerging dilemmas.

    Science.gov (United States)

    Laron, Zvi

    2011-06-01

    The history of pituitary growth hormone (GH) started 100 years ago but the isolation purification and determination of the chemical structure of the human GH (hGH) took another 50 years. Starting in 1957 hGH was extracted from cadaver pituitaries and its clinical use was restricted to severe GH deficient patient. With the invention of recombinant biosynthetic hGH in 1985; the indications for its use were extended. The major approved medications are GH deficiency and short statured children of various etiologies. This is a critical review of present and future use of human GH. To evaluate the effectiveness of the hGH treatment several pharmaceutical companies established postmarketing follow-up programs which are based on the reliability and cooperation of the treating physicians. Unfortunately they stop when the treatment is terminated and most studies refer to growth stimulation effectiveness during initial years but do not follow the children until final height. The long-term experience enabled to evaluate adverse effects (AE), the majority being due to large dosage. The most serious AE reported are increases in malignancies and early or late mortality in adult age. There is consensus that GH deficient children need replacement therapy. As long-term hGH treatment is expensive and the final height gains in non-GH deficient children small the cost-benefit indications to treat short children without a disease has been questioned. To avoid the need of daily injections, long-acting hGH preparations undergo clinical trials. The future will show their effectiveness and eventual adverse effects.

  7. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

  8. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Purpose: To determine the expression of corticotropin-releasing hormone (CRH) in psoriasis and ... Methods: Psoriasis and normal skin biopsy samples were obtained from three psoriatic and ... established in literature that stress signals such.

  9. Bone Mass in Young Adulthood Following Gonadotropin-Releasing Hormone Analog Treatment and Cross-Sex Hormone Treatment in Adolescents With Gender Dysphoria

    NARCIS (Netherlands)

    Klink, D.T.; Caris, M.G.; Heijboer, A.C.; van Trotsenburg, M.; Rotteveel, J.

    2015-01-01

    Context: Sex steroids are important for bone mass accrual. Adolescents with gender dysphoria (GD) treated with gonadotropin-releasing hormone analog (GnRHa) therapy are temporarily sex-steroid deprived until the addition of cross-sex hormones (CSH). The effect of this treatment on bone mineral

  10. The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

    Science.gov (United States)

    Root, A W; Shulman, D; Root, J; Diamond, F

    1986-01-01

    Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

  11. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  12. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Erika eComasco

    2014-12-01

    Full Text Available The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. This review summarizes the findings of thirty-four studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women’s brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

  13. Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners.

    Science.gov (United States)

    Yahiro, J; Glass, A R; Fears, W B; Ferguson, E W; Vigersky, R A

    1987-03-01

    Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 micrograms intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 micrograms intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were similar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We concluded that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in "stress-induced" or "psychogenic" amenorrhea.

  14. Hormonal therapy in female pattern hair loss

    Directory of Open Access Journals (Sweden)

    Kevin R. Brough

    2017-03-01

    Full Text Available Female pattern hair loss is the most common cause of hair loss in women and one of the most common problems seen by dermatologists. This hair loss is a nonscarring alopecia in which loss occurs on the vertex scalp, generally sparing the frontal hairline. Hair loss can have significant psychosocial effects on patients, and treatment can be long and difficult. The influence of hormones on the pathogenesis of female pattern hair loss is not entirely known. The purpose of this paper is to review physiology and potential hormonal mechanisms for the pathogenesis of female pattern hair loss. We also discuss the current hormonal and hormone-modifying therapies that are available to providers as they partner with patients to treat this frustrating issue.

  15. 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

  16. Hormone Therapy in Clinical Equine Practice.

    Science.gov (United States)

    McCue, Patrick M

    2016-12-01

    A wide variety of hormone therapies are used in clinical practice in the reproductive management of horses. The goal of this article is to review therapeutic options for a variety of clinical indications. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Hormone replacement therapy and risk of glioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper

    2013-01-01

    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  18. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

    1985-01-01

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation

  19. Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?

    Science.gov (United States)

    Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

    2016-03-01

    Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Spermatogenesis Abnormalities following Hormonal Therapy in Transwomen

    Directory of Open Access Journals (Sweden)

    Sirachai Jindarak

    2018-01-01

    Full Text Available Objective. To measure spermatogenesis abnormalities in transwomen at the time of sex reassignment surgery (SRS and to analyze the association between hormonal therapy duration and infertility severity. Design. Retrospective study. Setting. University hospital. Patients. One-hundred seventy-three transwomen who underwent SRS from January 2000 to December 2015. Interventions. All orchidectomy specimens were retrospectively reviewed and classified. History of hormonal therapy duration was retrieved from medical records. Main Outcome Measures. Histological examinations of orchidectomy specimens were performed to assess spermatogenesis. Results. One-hundred seventy-three orchidectomy specimens were evaluated. Histological examinations showed maturation arrest in 36.4%, hypospermatogenesis in 26%, Sertoli cell-only syndrome in 20.2%, normal spermatogenesis in 11%, and seminiferous tubule hyalinization in 6.4% of the specimens. Spermatogenesis abnormality severity was not associated with the total therapy duration (P=0.81 or patient age at the time of surgery (P=0.88. Testicular volumes and sizes were associated with spermatogenesis abnormality severity (P=0.001 and P=0.026, right testicle and left testicle, resp.. Conclusion(s. Feminizing hormonal treatment leads to reductions in testicular germ cell levels. All transwomen should be warned about this consequence, and gamete preservation should be offered before starting hormonal treatment.

  1. Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

    Science.gov (United States)

    Warren, W B; Gurewitsch, E D; Goland, R S

    1995-02-01

    We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

  2. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Purpose: To determine the expression of corticotropin-releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33. Methods: Psoriasis and normal skin biopsy samples were obtained from three ...

  3. 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.

  4. Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

    Science.gov (United States)

    Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

    2017-10-26

    Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

  5. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

    2002-06-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  6. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    International Nuclear Information System (INIS)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

    2002-01-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  7. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

    Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

  8. Hormone therapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jebelameli P

    1997-09-01

    Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

  9. Mathematical modeling of gonadotropin-releasing hormone signaling.

    Science.gov (United States)

    Pratap, Amitesh; Garner, Kathryn L; Voliotis, Margaritis; Tsaneva-Atanasova, Krasimira; McArdle, Craig A

    2017-07-05

    Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction. These are G q -coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. GnRH is secreted in short pulses and GnRH effects on its target cells are dependent upon the dynamics of these pulses. Here we overview GnRH receptors and their signaling network, placing emphasis on pulsatile signaling, and how mechanistic mathematical models and an information theoretic approach have helped further this field. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome

    NARCIS (Netherlands)

    Bayram, N.; van Wely, M.; Vandekerckhove, P.; Lilford, R.; van der Veen, F.

    2000-01-01

    BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in

  11. Radioimmunoassay of thyrotropin releasing hormone in plasma and urine

    International Nuclear Information System (INIS)

    Saito, Shiro; Musa, Kimitaka; Yamamoto, Suzuyo; Oshima, Ichiyo; Funato, Toyohiko

    1975-01-01

    A sensitive and specific radioimmunoassay has been developed capable of measuring thyrotropin releasing hormone (TRH) in extracted human plasma and urine. All of three TRH analogues tested had little cross-reactivity to antibody. Luteinizing hormone releasing hormone, lysine vasopressin, rat growth hormone and bovine albumin were without effect, but rat hypothalamic extract produced a displacement curve which was parallel to that obtained with the synthetic TRH. Sensitivity of the radioimmunoassay was 4 pg per tube with intraassay coefficient of variation of 6.2-9.7%. Synthetic TRH could be quantitatively extracted by methanol when added to human plasma in concentration of 25, 50 and 100 pg/ml. TRH immunoreactivity was rapidly reduced in plasma at 20 0 C than at 0 0 C, but addition of peptidase inhibitors, FOY-007 and BAL, prevented the inactivation of TRH for 3 hr at 0 0 C. The TRH in urine was more stable at 0 0 C than 20 0 C, and recovered 75+-4.6% at 24 hr after being added. The plasma levels of TRH were 19 pg/ml or less in normal adults and no sex difference was observed. The rate of disappearance of TRH administered i.v. from the blood could be represented as half-times of 4-12 min. Between 5.3-12.3% of the injected dose was excreted into urine within 1 hr as an immunoreactive TRH. These results indicate the usefulness of TRH radioimmunoassay for clinical investigation. (auth.)

  12. Effects of hormone therapy on brain structure

    OpenAIRE

    Kantarci, Kejal; Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay

    2016-01-01

    Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42?56 years, within 5?36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 ?g/d transdermal 17?-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active ...

  13. Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, S L; Loucks-Daniels, T L; Adler, L J; Chrousos, G P; Cameron, J L; Matthews, K A; Marcus, M D

    2000-04-01

    Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

  14. Hormone replacement therapy in cancer survivors: Utopia?

    Science.gov (United States)

    Angioli, Roberto; Luvero, Daniela; Armento, Grazia; Capriglione, Stella; Plotti, Francesco; Scaletta, Giuseppe; Lopez, Salvatore; Montera, Roberto; Gatti, Alessandra; Serra, Giovan Battista; Benedetti Panici, Pierluigi; Terranova, Corrado

    2018-04-01

    As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

    International Nuclear Information System (INIS)

    Menon, M.; Peegel, H.; Katta, V.

    1985-01-01

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

  16. Hormonal changes during GnRH analogue therapy in children with central precocious puberty

    DEFF Research Database (Denmark)

    Müller, J; Juul, A; Andersson, A M

    2000-01-01

    Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypoth......Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both...

  17. Hormones and tumour therapy: current clinical status and future developments in endocrine therapy of breast cancer

    International Nuclear Information System (INIS)

    Szepesi, T.; Schratter-Sehn, A.U.

    1982-01-01

    Postoperative adjuvant hormone therapy and hormone therapy in disseminated breast cancer will be discussed systematically. The classical ablative and additive endocrine therapeutic measures - with the exception of ovarectomy and gestagen therapy - are increasinlgy being replaced by antagonists. Individual chapters discuss recent experience with combined hormone-radiotherapy or hormone-chemotherapy. In addition, a successful therapy scheme for the treatment of disseminated breast cancer will be presented. (Author)

  18. Postmenopausal hormone therapy and subclinical cerebrovascular disease

    Science.gov (United States)

    Coker, L H.; Hogan, P E.; Bryan, N R.; Kuller, L H.; Margolis, K L.; Bettermann, K; Wallace, R B.; Lao, Z; Freeman, R; Stefanick, M L.; Shumaker, S A.

    2009-01-01

    Objective: The Women's Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS. Methods: We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of α = 0.05 was used. Results: In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo. Conclusions: Conjugated equine estrogen–based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials. GLOSSARY 3MSE = modified Mini-Mental State Examination; BMI = body mass index; CEE = conjugated equine estrogen; CVD = cerebrovascular disease; HT = hormone therapy; MCI = mild cognitive impairment; MPA

  19. alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and follicle-stimulating hormone secretion in the immature female rat.

    Science.gov (United States)

    Thyssen, S M; Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1997-06-01

    Polyamines play an essential role in tissue growth and differentiation, in body weight increment, in brain organization, and in the molecular mechanisms of hormonal action, intracellular signaling, and cell-to-cell communication. In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rats, was followed by prolonged high follicle-stimulating hormone (FSH) serum level and a delayed puberty onset. Those changes were relatively independent of body mass and did not impair posterior fertility. The present work studies the mechanisms and site of action of polyamine participation in FSH secretion during development. DFMO was injected in female rats between Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin-releasing hormone (GnRH) release were measured. The response to membrane depolarization was altered in DFMO hypothalami. Increased GnRH release in response to a low K+ concentration was evidenced. Adenohypophyses of the same treated prepubertal rats were perifused in vitro and the response to GnRH pulses was checked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in adenohypophyseal membranes from treated and control groups was quantified. A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the control group. In summary, DFMO treatment in a critical developmental period in the female rat impacts the immature GnRH neuronal network and immature gonadotropes. A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic explants. These events could explain the prolonged high FSH serum levels and delayed puberty onset seen in

  20. Hormone replacement therapy increases the risk of cranial meningioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper

    2013-01-01

    We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting.......We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting....

  1. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

    DEFF Research Database (Denmark)

    Vestergaard, P; Hermann, A P; Gram, J

    1997-01-01

    To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

  2. Risk of Stroke with Various Types of Menopausal Hormone Therapies

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Nielsen, Lars Hougaard; Keiding, Niels

    2017-01-01

    Background and Purpose: Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of reg...

  3. Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Alexander L. Pan

    2012-01-01

    Full Text Available Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.

  4. Growth Hormone Therapy in Adults with Prader-Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Karen S. Vogt

    2015-04-01

    Full Text Available Prader-Willi syndrome (PWS is characterized by hyperphagia, obesity if food intake is not strictly controlled, abnormal body composition with decreased lean body mass and increased fat mass, decreased basal metabolic rate, short stature, low muscle tone, cognitive disability, and hypogonadism. In addition to improvements in linear growth, the benefits of growth hormone therapy on body composition and motor function in children with PWS are well established. Evidence is now emerging on the benefits of growth hormone therapy in adults with PWS. This review summarizes the current literature on growth hormone status and the use of growth hormone therapy in adults with PWS. The benefits of growth hormone therapy on body composition, muscle strength, exercise capacity, certain measures of sleep-disordered breathing, metabolic parameters, quality of life, and cognition are covered in detail along with potential adverse effects and guidelines for initiating and monitoring therapy.

  5. Regulation of gonadotropin-releasing hormone neurons by glucose

    Science.gov (United States)

    Roland, Alison V.; Moenter, Suzanne M.

    2011-01-01

    Reproduction is influenced by energy balance, but the physiological pathways mediating their relationship have not been fully elucidated. As the central regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate numerous physiological signals, including metabolic cues. Circulating glucose levels regulate GnRH release and may in part mediate the effects of negative energy balance on fertility. Existing evidence suggests that neural pathways originating in the hindbrain, as well as in the hypothalamic feeding nuclei, transmit information concerning glucose availability to GnRH neurons. Here we review recent evidence suggesting that GnRH neurons may directly sense changes in glucose availability by a mechanism involving adenosine monophosphate-activated protein kinase (AMPK). These findings expand our understanding of how metabolic signaling in the brain regulates reproduction. PMID:21855365

  6. Should symptomatic menopausal women be offered hormone therapy?

    Science.gov (United States)

    Lobo, Rogerio A; Bélisle, Serge; Creasman, William T; Frankel, Nancy R; Goodman, Neil E; Hall, Janet E; Ivey, Susan Lee; Kingsberg, Sheryl; Langer, Robert; Lehman, Rebecca; McArthur, Donna Behler; Montgomery-Rice, Valerie; Notelovitz, Morris; Packin, Gary S; Rebar, Robert W; Rousseau, MaryEllen; Schenken, Robert S; Schneider, Diane L; Sherif, Katherine; Wysocki, Susan

    2006-01-01

    Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.

  7. Efficacy of chemotherapy after hormone therapy for hormone receptor-positive metastatic breast cancer.

    Science.gov (United States)

    Mori, Ryutaro; Nagao, Yasuko

    2014-01-01

    According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor-positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy-effective and hormone therapy-ineffective cases. Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2-positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy-ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of

  8. Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.

    Science.gov (United States)

    Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H

    2016-01-01

    To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. Published by Elsevier Inc.

  9. Nervus terminalis, olfactory nerve, and optic nerve representation of luteinizing hormone-releasing hormone in primates.

    Science.gov (United States)

    Witkin, J W

    1987-01-01

    The luteinizing hormone-releasing hormone (LHRH) system was examined immunocytochemically in olfactory bulbs of adult monkeys, including two New World species (squirrel monkey, Saimiri sciureus and owl monkey, Aotus trivirgatus) and one Old World species (cynomolgus macaque, Macaca fasciculata), and in the brain and nasal region of a fetal rhesus macaque Macaca mulatta. LHRH neurons and fibers were found sparsely distributed in the olfactory bulbs in all adult monkeys. There was more LHRH in the accessory olfactory bulb (which is absent in Old World monkeys). In the fetal macaque there was a rich distribution of LHRH neurons and fibers along the pathway of the nervus terminalis, anterior and ventral to the olfactory bulb, and in the nasal septum, with fibers branching into the olfactory epithelium. In addition, there were LHRH neurons and fibers in the optic nerve.

  10. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    International Nuclear Information System (INIS)

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-01-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E 2 ) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E 2 dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E 2 increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab

  11. Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects.

    Science.gov (United States)

    Bajusz, S; Kovacs, M; Gazdag, M; Bokser, L; Karashima, T; Csernus, V J; Janaky, T; Guoth, J; Schally, A V

    1988-03-01

    To eliminate the undesirable edematogenic effect of the luteinizing hormone-releasing hormone (LH-RH) antagonists containing basic D amino acids at position 6, exemplified by [Ac-D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH [Phe(pCl) indicates 4-chlorophenylalanine], analogs with D-ureidoalkyl amino acids such as D-citrulline (D-Cit) or D-homocitrulline (D-Hci) at position 6 were synthesized and tested in several systems in vitro and in vivo. HPLC analysis revealed that the overall hydrophobicity of the D-Cit/D-Hci6 analogs was similar to that of the basic D-Arg6 antagonists. In vitro, most of the analogs completely inhibited LH-RH-mediated luteinizing hormone release in perfused rat pituitary cell systems at an antagonist to LH-RH molar ratio of 5:1. In vivo, the most active peptides, [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Trp3,D-Cit6,D-Ala10]LH-RH [Nal(2) indicates 3-(2-naphthyl)alanine] and its D-Hci6 analog, caused 100% inhibition of ovulation in cycling rats in doses of 3 micrograms and suppressed the luteinizing hormone level in ovariectomized female rats for 47 hr when administered at doses of 25 micrograms. Characteristically, these peptides did not exert any edematogenic effects even at 1.5 mg/kg. These properties of the D-Cit/D-Hci6 antagonists may make them useful clinically.

  12. The effect of short-term cortisol changes on growth hormone responses to the pyridostigmine-growth-hormone-releasing-hormone test in healthy adults and patients with suspected growth hormone deficiency

    DEFF Research Database (Denmark)

    Andersen, M; Støving, R K; Hangaard, J

    1998-01-01

    BACKGROUND AND AIMS: The interaction between cortisol and growth hormone (GH)-levels may significantly influence GH-responses to a stimulation test. In order to systematically analyse the interaction in a paired design, it is necessary to use a test, which has been proven safe and reliable...... such as the pyridostigmine-growth-hormone-releasing-hormone (PD-GHRH) test. Three groups of subjects with a different GH-secretory capacity were included. STUDY A: Eight healthy adults were tested seven times, once with placebo throughout the examination and six times with the PD-GHRH test following no glucocorticoid......-responses to a PD-GHRH test were reduced in all individuals during acute stress-appropriate cortisol levels and the percentage reduction in GH-levels was independent of the GH-secretory capacity. Clinically, we found that peak GH-responses were not significantly affected by a short break in conventional HC therapy...

  13. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1992-01-01

    It has been shown that mice transgenic for human GH-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs, lactotrophs, and mammosomatotrophs, cells capable of producing both GH and PRL, by 8 months of age. We now report that GRH transgenic mice 10-24 months of age develop pituitary...... adenomas, which we characterized by histology, immunohistochemistry, in situ hybridization, and electron microscopy. Of 13 animals examined, all developed GH-immunoreactive neoplasms that had diffuse positivity for GH mRNA by in situ hybridization. Eleven also contained PRL immunoreactivity; in situ...

  14. Postmenopausal hormone therapy and Alzheimer disease

    Science.gov (United States)

    Tuppurainen, Marjo; Rikkonen, Toni; Kivipelto, Miia; Soininen, Hilkka; Kröger, Heikki; Tolppanen, Anna-Maija

    2017-01-01

    Objective: To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD). Methods: Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47–56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999–2009). The study population included 8,195 women (227 cases of incident AD). Results: Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68–1.2, 0.99/0.75–1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31–0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome. Conclusions: Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use. PMID:28202700

  15. Hormone therapy after the Women's Health Initiative: a qualitative study

    Directory of Open Access Journals (Sweden)

    Holtrop Jodi S

    2006-10-01

    Full Text Available Abstract Background Publication of results from the Women's Health Initiative study in July 2002 was a landmark event in biomedical science related to postmenopausal women. The purpose of this study was to describe the impact of new hormone therapy recommendations on patients' attitudes and decision-making in a primary care practice. Methods A questionnaire including structured and open-ended questions was administered in a family practice office waiting room from August through October 2003. Rationale for taking or not taking hormone therapy was specifically sought. Women 50–70 years old attending for office visits were invited to participate. Data were analyzed qualitatively and with descriptive statistics. Chart review provided medication use rates for the entire practice cohort of which the sample was a subset. Results Respondents (n = 127 were predominantly white and well educated, and were taking hormone therapy at a higher rate (38% than the overall rate (26% for women of the same age range in this practice. Belief patterns about hormone therapy were, in order of frequency, 'use is risky', 'vindication or prior beliefs', 'benefit to me outweighs risk', and 'unaware of new recommendations'. Twenty-eight out of 78 women continued hormones use after July 2002. Of 50 women who initially stopped hormone therapy after July 2002, 12 resumed use. Women who had stopped hormone therapy were a highly symptomatic group. Responses with emotional overtones such as worry, confusion, anger, and grief were common. Conclusion Strategies for decision support about hormone therapy should explicitly take into account women's preferences about symptom relief and the trade-offs among relevant risks. Some women may need emotional support during transitions in hormone therapy use.

  16. Hormone replacement therapy in Denmark, 1995-2004

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Lidegaard, Ojvind; Møller, Lisbeth Nørgaard

    2007-01-01

    Recently, the Danish National Register of Medicinal Product Statistics (NRM) was opened for research purposes, and therefore, on an individual basis, can merge with other national registers. The aim of this study was to analyse the use of hormones based on the individual data of the entire Danish...... female population, with the focus on a detailed evaluation of specific hormone regimens and factors associated with systemic hormone replacement therapy (HRT)....

  17. The effect of ovarian steroid feedback upon radioimmunoreactive luteinizing hormone releasing hormone in the hypothalamus

    International Nuclear Information System (INIS)

    Yanaihara, Takumi; Arai, Kiyoshi; Kanazawa, Motomi; Okinaga, Shoichi; Yanaihara, Noboru

    1975-01-01

    A radioimmunoassay (RIA) method for luteinizing hormone (LH) releasing hormone (RH) utilizing rabbit antiserum against synthetic (Glu 1 )-LH-RH coupled with human serum albumin at the N-terminus, is described. This assay system for LH-RH also cross-reacted with several LH-RH analogues or fragments, but not with pituitary trophic hormones. The assay was performed on the hypothalamic extracts of adult ovariectomized rats and female immature rats which had been treated with estradiol. The FSH and LH levels in the pituitary gland and serum of the same animals were determined by RIA. The radioimmunoreactive LH-RH content of the stalk median eminence markedly increased seven days after ovariectomy. The serum levels and the pituitary contents of FSH and LH of the same rats were also significantly augmented. In immature rats, the hypothalamic content of LH-RH, as measured by RIA, was significantly increased one hour after the injection of estradiol. The FSH and LH levels in the pituitary showed a significant rise after 7 hours. (auth.)

  18. Diseases associated with growth hormone-releasing hormone receptor (GHRHR) mutations.

    Science.gov (United States)

    Martari, Marco; Salvatori, Roberto

    2009-01-01

    The growth hormone (GH)-releasing hormone (GHRH) receptor (GHRHR) belongs to the G protein-coupled receptors family. It is expressed almost exclusively in the anterior pituitary, where it is necessary for somatotroph cells proliferation and for GH synthesis and secretion. Mutations in the human GHRHR gene (GHRHR) can impair ligand binding and signal transduction, and have been estimated to cause about 10% of autosomal recessive familial isolated growth hormone deficiency (IGHD). Mutations reported to date include five splice donor site mutations, two microdeletions, two nonsense mutations, seven missense mutations, and one mutation in the promoter. These mutations have an autosomal recessive mode of inheritance, and heterozygous individuals do not show signs of IGHD, although the presence of an intermediate phenotype has been hypothesized. Conversely, patients with biallelic mutations have low serum insulin-like growth factor-1 and GH levels (with absent or reduced GH response to exogenous stimuli), resulting--if not treated--in proportionate dwarfism. This chapter reviews the biology of the GHRHR, the mutations that affect its gene and their effects in homozygous and heterozygous individuals. Copyright © 2009 Elsevier Inc. All rights reserved.

  19. Proton therapy of hormone-secreting hypophyseal adenomas: gluconeogenesis assessment

    International Nuclear Information System (INIS)

    Konnova, L.A.; Konnov, B.A.; Mel'nikov, L.A.; Lebedeva, N.A.

    1993-01-01

    Analysis of blood plasma aminograms of patients with hormone secreting hypophyseal adenomas (somatotropinomas and prolactinomas), that were obtained before and after a course of proton therapy, has confirmed the gluconeogenic effect of hypophyseal hormones and evidenced the relationship between this effect and dismetabolism of some amino acids

  20. Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

    Science.gov (United States)

    According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

  1. Endocrine therapy use among elderly hormone receptor-pos...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Clinical guidelines recommend that women with hormone-receptor positive breast cancer receive endocrine therapy (selective estrogen receptor modulators or aromatase...

  2. Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

    Science.gov (United States)

    ... hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from ... Advertising and sponsorship opportunities Reprint Permissions A single copy of these materials may be reprinted for noncommercial ...

  3. Incretin hormones as a target for therapy

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2016-01-01

    Incretin hormones are responsible for the incretin effect, which is the amplification of insulin secretion when nutrients are taken in orally, as opposed to intravenously.......Incretin hormones are responsible for the incretin effect, which is the amplification of insulin secretion when nutrients are taken in orally, as opposed to intravenously....

  4. Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

    NARCIS (Netherlands)

    van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

    2009-01-01

    Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

  5. Effects of hormone therapy on brain structure

    Science.gov (United States)

    Tosakulwong, Nirubol; Lesnick, Timothy G.; Zuk, Samantha M.; Gunter, Jeffrey L.; Gleason, Carey E.; Wharton, Whitney; Dowling, N. Maritza; Vemuri, Prashanthi; Senjem, Matthew L.; Shuster, Lynne T.; Bailey, Kent R.; Rocca, Walter A.; Jack, Clifford R.; Asthana, Sanjay; Miller, Virginia M.

    2016-01-01

    Objective: To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women. Methods: Participants (aged 42–56 years, within 5–36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured. Results: Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = −0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups. Conclusions: Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. Classification of evidence: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo. PMID:27473135

  6. Different growth hormone (GH) response to GH-releasing peptide and GH-releasing hormone in hyperthyroidism.

    Science.gov (United States)

    Ramos-Dias, J C; Pimentel-Filho, F; Reis, A F; Lengyel, A M

    1996-04-01

    Altered GH responses to several pharmacological stimuli, including GHRH, have been found in hyperthyroidism. The mechanisms underlying these disturbances have not been fully elucidated. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release both in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. The aim of this study was to evaluate the effects of GHRP-6 on GH secretion in patients with hyperthyroidism (n = 9) and in control subjects (n = 9). Each subject received GHRP-6 (1 microg/kg, iv), GHRH (100 microg, iv), and GHRP-6 plus GHRH on 3 separate days. GH peak values (mean +/- SE; micrograms per L) were significantly lower in hyperthyroid patients compared to those in control subjects after GHRH alone (9.0 +/- 1.3 vs. 27.0 +/- 5.2) and GHRP-6 plus GHRH (22.5 +/- 3.5 vs. 83.7 +/- 15.2); a lack of the normal synergistic effect of the association of both peptides was observed in thyrotoxicosis. However, a similar GH response was seen in both groups after isolated GHRP-6 injection (31.9 +/- 5.7 vs. 23.2 +/- 3.9). In summary, we have shown that hyperthyroid patients have a normal GH response to GHRP-6 together with a blunted GH responsiveness to GHRH. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

  7. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    OpenAIRE

    Xue, Peng; Wang, Yan; Yang, Jie; Li, Yukun

    2013-01-01

    Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochr...

  8. Progressive pituitary hormone deficiency following radiation therapy in adults

    International Nuclear Information System (INIS)

    Loureiro, Rafaela A.; Vaisman, Mario

    2004-01-01

    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)

  9. Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    International Nuclear Information System (INIS)

    Rettori, V.; McCann, S.M.; Gimeno, M.F.; Karara, A.; Gonzalez, M.C.

    1991-01-01

    Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E 2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E 2 -mediated release of LHRH

  10. A different approach to the radioimmunoassay of thyrotropin releasing hormone

    International Nuclear Information System (INIS)

    Visser, T.J.; Klootwijk, W.; Docter, R.; Hennemann, G.

    1977-01-01

    Thyrotropin releasing hormone (TRH) was linked to hemocyanin by means of a dinitrophenylene moiety. TRH (pGlu-His-Pro-NH 2 ) was made to react with a large excess of 1,5-difluoro-2,4-dinitrobenzene to yield Nsup(im)-[5-fluoro-2,4-dinitrophenyl]TRH. After removal of excess reagent the derivative was coupled to hemocyanin with a minimum of side-reactions. From two rabbits out of four immunized with this material valuable antisera were obtained, which were used in the radioimmunoassay of the hypothalamic hormone at a final dilution of 1:7,500 and 1:15,000, respectively. The properties, especially with regard to specificity, of these antisera were studied and compared with another antiserum, which was obtained using a conjugate having TRH linked to thyroglobulin via a p-azophenyl-acetyl moiety. Despite the difference between the derivatives, i.e. the nature and the point of attachment of the side chains, the specificities of the assays were very similar. Deamidation of TRH, deletion of either one of the terminal residues, hydrolysis of the lactam of the pyroglutamyl residue, and replacing Pro-NH 2 by Pro-Gly-NH 2 or by an octapeptide chain yield peptides with strongly diminished cross-reactivities. However, Nsup(im)-benzyl-TRH and pGlu-Phe-Pro-NH 2 were 5-10 times as active as TRH probably due to a closer physico-chemical similarity to the arrangement of the haptens in the conjugates. This suggests that the sensitivity of the radioimmunoassay may be increased markedly by conversion of TRH into the Nsup(im)-dinitrophenyl derivative and by using a related compound for radioiodination. (orig.) [de

  11. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    DEFF Research Database (Denmark)

    Comasco, Erika; Frøkjær, Vibe; Sundström-Poromaa, Inger

    2014-01-01

    The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuat......The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone...... fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri......-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain....

  12. Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

    Science.gov (United States)

    Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

    2013-11-01

    Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep. © 2013 International Society for Neurochemistry.

  13. Thyroid-hormone concentrations after radioiodine therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Tamagna, E.I.; Levine, G.A.; Hershman, J.M.

    1979-01-01

    Fourteen hyperthyroid patients (11 men, three women), ages 28 to 66, were followed with serial measurements of serum thyroid hormone levels for 1 mo after therapy with I-131. Twelve patients had diffuse toxic goiters (25 to 70 g in size); two patients had multinodular glands (40 to 100 g). The patients were taking no antithyroid medications; ten patients were treated with propranolol. All patients received the equivalent of 5000 rad, except the two with multinodular glands, who received larger doses. There was no consistent pattern of serum T 4 and T 3 levels after the I-131 therapy. For the entire group, there was no significant increase of the mean serum hormone concentration. One group (three patients) had a mean T 4 increase of 28% and a T 3 increase of 91% above baseline at Days 10--11. Seven patients had minimal increases of hormone levels at Days 2--3, and a third group (four paients) had no increase of thyroid hormones after I-131 therapy. The patients with no rise in hormone concentrations had smaller goiters than the other groups. There was no correlation of the dose of radioactive iodine, or of the initial hormone concentration, with the rises or declines of T 4 and T 3 levels after I-131 therapy. Radioiodine therapy caused no significant increase of serum T 4 and T 3 concentrations in the majority of patients

  14. The influence of hormone therapies on colon and rectal cancer.

    Science.gov (United States)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels; Løkkegaard, Ellen; Kjær, Susanne Krüger

    2016-05-01

    Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0.83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone users were at lower risk of advanced stage of colorectal cancer, which seems supportive for a causal association between hormone therapy and colorectal cancer.

  15. Melatonin improves memory acquisition under stress independent of stress hormone release

    OpenAIRE

    Rimmele, U; Spillmann, M; Bärtschi, C; Wolf, O T; Weber, C S; Ehlert, Ulrike; Wirtz, P H

    2009-01-01

    RATIONALE: Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. OBJECTIVES: We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans. As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function. MATERIALS AND METHODS: Fifty healthy young men received a single oral dose of either 3...

  16. Short-chain analogs of luteinizing hormone-releasing hormone containing cytotoxic moieties.

    Science.gov (United States)

    Janáky, T; Juhász, A; Rékási, Z; Serfözö, P; Pinski, J; Bokser, L; Srkalovic, G; Milovanovic, S; Redding, T W; Halmos, G

    1992-11-01

    Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line.

  17. Acute effects of clonidine and growth-hormone-releasing hormone on growth hormone secretion in patients with hyperthyroidism.

    Science.gov (United States)

    Giustina, A; Buffoli, M G; Bussi, A R; Wehrenberg, W B

    1991-01-01

    Patients with hyperthyroidism have reduced growth hormone (GH) responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of clonidine on GH secretion has been suggested to depend on an enhancement of hypothalamic GH-releasing hormone (GHRH) release. The aim of our study was to evaluate the effects of clonidine and GHRH on GH secretion in patients with hyperthyroidism. Eight hyperthyroid females with recent diagnosis of Graves' disease (age range 20-55 years, body mass index range 19.2-26.2 kg/m2) and 6 healthy female volunteers (age range 22-35 years, body mass index range 19-25 kg/m2) underwent two experimental trials at no less than 7-day intervals: (a) an intravenous infusion of clonidine 150 micrograms in 10 ml of saline, or (b) a bolus intravenous injection of human GHRH (1-29)NH2, 100 micrograms in 1 ml of saline. Hyperthyroid patients showed blunted GH peaks after clonidine (7.1 +/- 1.7 micrograms/l) as compared to normal subjects receiving clonidine (28.5 +/- 4.9 micrograms/l, p less than 0.05). GH peaks after GHRH were also significantly lower in hyperthyroid subjects (8.0 +/- 1.7 micrograms/l) as compared to normal subjects receiving GHRH (27.5 +/- 4.4 micrograms/l, p less than 0.05). No significant differences in the GH values either after clonidine or GHRH were observed in the two groups of subjects examined. Our data demonstrate that the GH responses to clonidine as well as to GHRH in patients with hyperthyroidism are inhibited in a similar fashion with respect to normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Thyrotropin-releasing hormone (TRH) reverses hyperglycemia in rat

    International Nuclear Information System (INIS)

    Luo Luguang; Luo, John Z.Q.; Jackson, Ivor M.D.

    2008-01-01

    Hyperglycemia in thyrotropin-releasing hormone (TRH) null mice indicates that TRH is involved in the regulation of glucose homeostasis. Further, TRH levels in the pancreas peak during the stages of late embryonic and early neonatal β cell development. These observations are consistent in linking TRH to islet cell proliferation and differentiation. In this study, we examined the effect of TRH administration in damaged pancreatic rat (streptozotocin, STZ) to determine whether TRH could improve damaged pancreatic β cells function. We hypothesize that TRH is able to reverse STZ-induced hyperglycemia by increasing pancreatic islet insulin content, preventing apoptosis, and potentially induce islet regeneration. It was found that following intra-peritoneal (ip) injection, TRH (10 μg/kg body weight (bwt)) reverses STZ (65 mg/kg bwt)-induced hyperglycemia (TRH given 3 days after STZ injection). Increased circulating insulin levels and insulin content in extracted pancreas suggests that TRH reversed STZ-induced hyperglycemia through improving pancreatic islet β cell function. Further studies show a significantly lower level of apoptosis in islets treated with TRH as well as the presence of proliferation marker nestin and Brdu, suggesting that the TRH has the potential to prevent apoptosis and stimulate islet proliferation

  19. Endocrinology and the brain: corticotropin-releasing hormone signaling.

    Science.gov (United States)

    Inda, Carolina; Armando, Natalia G; Dos Santos Claro, Paula A; Silberstein, Susana

    2017-08-01

    Corticotropin-releasing hormone (CRH) is a key player of basal and stress-activated responses in the hypothalamic-pituitary-adrenal axis (HPA) and in extrahypothalamic circuits, where it functions as a neuromodulator to orchestrate humoral and behavioral adaptive responses to stress. This review describes molecular components and cellular mechanisms involved in CRH signaling downstream of its G protein-coupled receptors (GPCRs) CRHR1 and CRHR2 and summarizes recent findings that challenge the classical view of GPCR signaling and impact on our understanding of CRHRs function. Special emphasis is placed on recent studies of CRH signaling that revealed new mechanistic aspects of cAMP generation and ERK1/2 activation in physiologically relevant contexts of the neurohormone action. In addition, we present an overview of the pathophysiological role of the CRH system, which highlights the need for a precise definition of CRHRs signaling at molecular level to identify novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. © 2017 The authors.

  20. Function of gonadotropin-releasing hormone in olfaction.

    Science.gov (United States)

    Wirsig-Wiechmann, C R

    2001-06-01

    Gonadotropin-releasing hormone (GnRH) is present within neurons of the nervus terminalis, the zeroeth cranial nerve. In all vertebrate species, except in sharks where it is a separate nerve, the nervus terminalis consists of a chain of neurons embedded within olfactory or vomeronasal nerves in the nasal cavity. The function of the GnRH component of the nervus terminalis is thought to be neuromodulatory. Our research on GnRH effects on olfaction confirms this hypothesis. The processes of GnRH neural cell bodies located within chemosensory nerves project centrally into the ventral forebrain and peripherally into the lamina propria of the nasal chemosensory mucosa. GnRH receptors are expressed by chemosensory neurons as shown by RT-PCR/Southern blotting and GnRH agonist binding studies. Patch-clamp studies have shown that GnRH alters the responses of isolated chemosensory neurons to natural or electrophysiological stimulation through the modulation of voltage-gated and receptor-gated channels. Behavioral experiments demonstrate that interfering with the nasal GnRH system leads to deficits in mating behavior. These studies suggest that the function of the intranasal GnRH system is to modify olfactory information, perhaps at reproductively auspicious times. We speculate that the purpose of this altered olfactory sense is to make pheromones more detectable and salient.

  1. Gonadotrophin releasing hormone antagonist in IVF/ICSI

    Directory of Open Access Journals (Sweden)

    M S Kamath

    2008-01-01

    Full Text Available Objective : To study the efficacy of gonadotrophin releasing hormone (GnRH antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI cycles. Type of Study : Observational study. Setting: Reproductive Medicine Unit, Christian Medical College Hospital, Vellore, Tamil Nadu. Materials and Methods: GnRH antagonists were introduced into our practice in November 2005. Fifty-two women undergoing the antagonist protocol were studied and information gathered regarding patient profile, treatment parameters (total gonadotrophin dosage, duration of treatment, and oocyte yield, and outcomes in terms of embryological parameters (cleavage rates, implantation rates and clinical pregnancy. These parameters were compared with 121 women undergoing the standard long protocol. The costs between the two groups were also compared. Main Outcome : Clinical pregnancy rate. Results : The clinical pregnancy rate per embryo transfer in the antagonist group was 31.7% which was comparable to the clinical pregnancy rate in women undergoing the standard long protocol (30.63%. The costs between the two groups were comparable. Conclusions : GnRH antagonist protocol was found to be effective and comparable to the standard long protocol regimen. In addition it was simple, convenient, and patient friendly.

  2. Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis.

    Science.gov (United States)

    Tranoulis, Anastasios; Laios, Alexandros; Pampanos, Andreas; Yannoukakos, Drakoulis; Loutradis, Dimitrios; Michala, Lina

    2018-04-01

    To systematically review and appraise the existing evidence in relation to the efficacy and safety of pulsatile gonadotropin-releasing hormone (pGnRH) for the treatment of women with hypothalamic amenorrhea (HA). Systematic review and meta-analysis. Not applicable. A total of 35 studies (three randomized and 32 observational) encompassing 1,002 women with HA. None. Primary outcomes: ovulation rate (OvR), pregnancy per ovulatory cycle rate (POR), and live birth per ovulatory cycle rate (LBOR). multiple gestation (MG), ovarian hyperstimulation syndrome (OHSS), and superficial thrombophlebitis (ST) rates. The summary measures were expressed as proportions and 95% confidence intervals (CI). Pulsatile GnRH treatment appears to achieve high OvRs. A trend toward high PORs and LBORs among women with HA is demonstrated. SC pGnRH achieves comparable OvR compared with IV pGnRH. The incidence of OHSS is low and of mild severity. Treatment with pGnRH is associated with low but slightly higher MG rates compared with the general population. IV administered pGnRH is rarely associated with ST. The high OvRs leading to a high rate of singleton pregnancies and the low likelihood of OHSS render the pGnRH treatment modality both effective and safe for the treatment of women with HA of either primary or secondary origin. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

    Directory of Open Access Journals (Sweden)

    Christian Cortés-Campos

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

  4. A regulator of G Protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH-stimulated luteinizing hormone (LH secretion

    Directory of Open Access Journals (Sweden)

    Musgrove Lois C

    2001-11-01

    Full Text Available Abstract Background Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. Luteinizing hormone secretion is regulated both by alterations in gonadotrope responsiveness to hypothalamic gonadotropin releasing hormone and by alterations in gonadotropin releasing hormone secretion. The mechanisms that determine gonadotrope responsiveness are unknown but may involve regulators of G protein signaling (RGSs. These proteins act by antagonizing or abbreviating interaction of Gα proteins with effectors such as phospholipase Cβ. Previously, we reported that gonadotropin releasing hormone-stimulated second messenger inositol trisphosphate production was inhibited when RGS3 and gonadotropin releasing hormone receptor cDNAs were co-transfected into the COS cell line. Here, we present evidence for RGS3 inhibition of gonadotropin releasing hormone-induced luteinizing hormone secretion from cultured rat pituitary cells. Results A truncated version of RGS3 (RGS3T = RGS3 314–519 inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production more potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound more 35S-Gqα than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated 3H-inositol phosphate accumulation, consistent with a molecular site of action at the Gqα protein. Conclusions RGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gqα protein function. A version of RGS3 that is amino

  5. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  6. Active immunization against gonadotropin-releasing hormone : an effective tool to block the fertility axis in mammals

    NARCIS (Netherlands)

    Turkstra, Jouwert Anne

    2005-01-01

    Gonadotropin releasing hormone (GnRH) plays a pivotal role in fertility and reproduction in mammals. It induces the release of luteinising hormone (LH) en follicle stimulating hormone (FSH) from the pituitary. These hormones are responsible for gonadal steroid production and indirectly for

  7. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    Energy Technology Data Exchange (ETDEWEB)

    Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete, Kwara State (Nigeria); Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Electronics and Electricals Engineering, Nigerian Turkish Nile University, Abuja (Nigeria); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY 10453 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Malatesta, K. [Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States)

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement.

  8. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    International Nuclear Information System (INIS)

    Obayemi, J.D.; Dozie-Nwachukwu, S.; Danyuo, Y.; Odusanya, O.S.; Anuku, N.; Malatesta, K.; Soboyejo, W.O.

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement

  9. Corticotropin releasing hormone and imaging, rethinking the stress axis

    International Nuclear Information System (INIS)

    Contoreggi, Carlo

    2015-01-01

    The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems have surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we've seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and

  10. Variation in the psychosocial determinants of the intention to prescribe hormone therapy prior to the release of the Women's Health Initiative trial: a survey of general practitioners and gynaecologists in France and Quebec

    Directory of Open Access Journals (Sweden)

    Turcot Lucile

    2005-09-01

    Full Text Available Abstract Background Theory-based approaches are advocated to improve our understanding of prescription behaviour. This study is an application of the theory of planned behaviour (TPB with additional variables. It was designed to assess which variables were associated with the intention to prescribe hormone therapy (HT. In addition, variations in the measures across medical specialities (GPs and gynaecologists and across countries (France and Quebec were investigated. Methods A survey among 2,000 doctors from France and 1,044 doctors from Quebec was conducted. Data were collected by means of a self-administered questionnaire. A clinical vignette was used to elicit doctors' opinions. The following TPB variables were assessed: attitude, subjective norm, perceived behavioural control, attitudinal beliefs, normative beliefs and power of control beliefs. Additional variables (role belief, moral norm and practice pattern-related factors were also assessed. A stepwise logistic regression was used to assess which variables were associated with the intention to prescribe HT. GPs and gynaecologists were compared to each other within countries and the two countries were compared within the specialties. Results Overall, 1,085 doctors from France returned their questionnaire and 516 doctors from Quebec (response rate = 54% and 49%, respectively. In the overall regression model, power of control beliefs, moral norm and role belief were significantly associated with intention (all at p p p p p p p p = 0.01; and for gynaecologists in France, power of control beliefs (p p Conclusion In both countries, compared with GPs, intention to prescribe HT was higher for gynaecologists. Psychosocial determinants of doctors' intention to prescribe HT varied according to the specialty and the country thus, suggesting an influence of contextual factors on these determinants.

  11. Abnormal Bleeding during Menopause Hormone Therapy: Insights for Clinical Management

    Directory of Open Access Journals (Sweden)

    Sebastião Freitas De Medeiros

    2013-01-01

    Full Text Available Objective Our objective was to review the involved mechanisms and propose actions for controlling/treating abnormal uterine bleeding during climacteric hormone therapy. Methods A systemic search of the databases SciELO, MEDLINE, and Pubmed was performed for identifying relevant publications on normal endometrial bleeding, abnormal uterine bleeding, and hormone therapy bleeding. Results Before starting hormone therapy, it is essential to exclude any abnormal organic condition, identify women at higher risk for bleeding, and adapt the regimen to suit eachwoman's characteristics. Abnormal bleeding with progesterone/progestogen only, combined sequential, or combined continuous regimens may be corrected by changing the progestogen, adjusting the progestogen or estrogen/progestogen doses, or even switching the initial regimen to other formulation. Conclusion To diminish the occurrence of abnormal bleeding during hormone therapy (HT, it is important to tailor the regimen to the needs of individual women and identify those with higher risk of bleeding. The use of new agents as adjuvant therapies for decreasing abnormal bleeding in women on HT awaits future studies.

  12. Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors.

    Science.gov (United States)

    Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C; Munson, P J; Rodbard, D

    1979-12-01

    Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions.

  13. Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism.

    Science.gov (United States)

    Giustina, A; Bussi, A R; Legati, F; Bossoni, S; Licini, M; Schettino, M; Zuccato, F; Wehrenberg, W B

    1992-12-01

    Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

  14. Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

    Science.gov (United States)

    Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

    2015-05-01

    To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

  15. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  16. Psychoneuromedulator role of corticotrophin releasing hormone in PCOS

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2016-10-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is a common complex condition in women associated with reproductive and metabolic systems and also psychological disorders. There is considerable evidence to suggest that the sympathetic nervous system is involved in PCO and metabolic syndromes. Noradrenalin (NA, corticotrophin releasing hormone (CRH and nerve growth factor (NGF are the strong stimulants for two axes: hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-ovarian (HPO axes which are regulators for the female reproductive system. Following previous studies on sympathetic nervous system over activity in PCOS, the main purpose of this study is to evaluate the role of CRH and NGF as two important findings from the perspective of the psycho-emotional. Methods: This case-control study was conducted in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran, Iran in the September of 2011. 170 women participated in this study. The diagnosis of PCOS was made according to the joint criteria of the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine (ESHRE/ASRM. All women have 20-40 years of age and body mass index (BMI of less than 28. Demographic questionnaire was used in this study and blood sample was obtained from all participants before 8AM. All analysis was done in SPSS software, version 19 (IBM SPSS, Armonk, NY, USA. P-value less than 0.05 considered as significant level. Results: Serum levels of CRH and NGF in patients with polycystic ovary was significantly lower than the control group (P< 0.001. This reduction can disrupt two neural axes: the sympathetic nervous system (SAS and hypothalamus-pituitary-adrenal (HPA. These axes have a fundamental role in psycho-emotional reactions in women with PCOS. Moreover, using demographic questionnaire quantitative and qualitative characteristics of the population studied, the results of which are reported in the regression

  17. The olfactory gonadotropin-releasing hormone immunoreactive system in mouse.

    Science.gov (United States)

    Jennes, L

    1986-10-29

    The olfactory gonadotropin-releasing hormone (GnRH) system in mice was studied with immunofluorescence in combination with lesions of the olfactory bulb and retrograde transport of horseradish peroxidase (HRP) which was administered intravascularly, intranasally or into the subarachnoid space. GnRH-positive neurons were located in the two major branches forming the septal roots of the nervus terminalis, in the ganglion terminale, within the fascicles of the nervus terminalis throughout its extent, in a conspicuous band which connects the ventral neck of the caudal olfactory bulb with the accessory olfactory bulb and in the nasal mucosa. GnRH-positive fibers were seen in all areas in which neurons were found, i.e. in the rostral septum, the ganglion and nervus terminalis and in the nasal subepithelium. In addition, a broad bundle of fibers was observed to surround the entire caudal olfactory bulb, connecting the rostral sulcus rhinalis with the ventrocaudal olfactory bulb. Fibers were seen in close association with the main and accessory olfactory bulb, with the fila olfactoria and with the nasal mucosa. Throughout the olfactory bulb and the nasal epithelium, an association of GnRH fibers with blood vessels was apparent. Intravascular and intranasal injection of HRP resulted in labeling of certain GnRH neurons in the septal roots of the nervus terminalis, the ganglion terminale, the nervus terminalis, the caudal ventrodorsal connection and in the accessory olfactory bulb. After placement of HRP into the subarachnoid space dorsal to the accessory olfactory bulb, about 50% of the GnRH neurons in the accessory olfactory bulb and in the ventrodorsal connection were labeled with HRP. Also, a few GnRH neurons in the rostral septum, the ganglion terminale and in the fascicles of the nervus terminalis had taken up the enzyme. Lesions of the nervus terminalis caudal to the ganglion terminale resulted in sprouting of GnRH fibers at both sites of the knife cut. Lesions rostral

  18. [Effects of growth hormone replacement therapy on bone metabolism].

    Science.gov (United States)

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  19. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

  20. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells.

  1. In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

    International Nuclear Information System (INIS)

    Rettori, V.; Aguila, M.C.; McCann, S.M.; Gimeno, M.F.; Franchi, A.M.

    1990-01-01

    Previous in vivo studies have shown that Δ 9 -tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E 2 (PGE 2 ) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE 2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE 2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release

  2. QUALITY OF LIFE, COUNSELLING AND HORMONE REPLACEMENT THERAPY

    Directory of Open Access Journals (Sweden)

    Nena Kopčavar Guček

    2008-12-01

    Quality of life in menopause is a result of many factors and therefore it is very individual.Hormone replacement therapy is one of the possibilities of improvement. Therefore, it isessential that a woman is adequately informed about all the advantages and risks of thehormonal replacement therapy. Only an informed patient can be a partner in shareddecision making about the improvement of quality of life

  3. Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions

    Science.gov (United States)

    ... and gallbladder disease. It also can increase the risk of dementia and urinary incontinence. The Task Force found that taking estrogen alone ... has important potential harms. It can increase the risk of stroke, blood clots, gallbladder disease, and urinary ... a fracture Combined Hormone Therapy ...

  4. Hormone therapy in ovarian granulosa cell tumors: a systematic review

    NARCIS (Netherlands)

    van Meurs, Hannah S.; van Lonkhuijzen, Luc R. C. W.; Limpens, Jacqueline; van der Velden, Jacobus; Buist, Marrije R.

    2014-01-01

    This systematic review assessed the effectiveness of hormone therapy (HT) in patients with a granulosa cell tumor (GCT) of the ovary. Medline (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials (CENTRAL), prospective trial registers and PubMed (as supplied by publisher-subset)

  5. Therapy for obesity based on gastrointestinal hormones

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Christensen, Mikkel; Knop, Filip K

    2011-01-01

    for the treatment of type 2 diabetes. In contrast to other antidiabetic treatments, these agents have a positive outcome profile on body weight. Worldwide there are 500 million obese people, and 3 million are dying every year from obesity-related diseases. Recently, incretin-based therapy was proposed...... for the treatment of obesity. Currently two different incretin therapies are widely used in the treatment of type 2 diabetes: 1) the GLP-1 receptor agonists which cause significant and sustained weight loss in overweight patients, and 2) dipeptidyl peptidase 4 (DPP-4) inhibitors being weight neutral. These findings...... have led to a greater interest in the physiology of intestinal peptides with potential weight-reducing properties. This review discusses the effects of the incretin-based therapies in obesity, and provides an overview of intestinal peptides with promising effects as potential new treatments for obesity....

  6. Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.

    Science.gov (United States)

    Noel, G L; Dimond, R C; Earll, J M; Frantz, A G

    1976-05-01

    Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.

  7. Hormonal therapy after the operation for catamenial pneumothorax - is it always necessary?

    Science.gov (United States)

    Subotic, D; Mikovic, Z; Atanasijadis, N; Savic, M; Moskovljevic, D; Subotic, D

    2016-04-14

    Our recent clinical observations put into question the routine hormonal therapy for pneumothorax recurrence prevention, in patients operated for catamenial pneumothorax (CP). Retrospective review of the treatment of four women operated for CP in a recent 32-months period. The four presented patients with CP represent 4.8 % of the overall number of patients operated for spontaneous pneumothorax and 19 % of women operated for pneumothorax in the same period. In all patients, typical multiple diaphragm holes existed. The involved part of the diaphragm was removed with diaphragm suture in three patients, whilst in one patient, a diaphragm placation was done. Endometriosis was histologically confirmed in two patients. During the follow-up period of 6-43 months, none of the patients underwent a postoperative hormonal therapy for different reasons, and in none of them the pneumothorax recurrence occurred. The clinical course of these patients, with the absence of the pneumothorax recurrence despite the omission of the hormonal treatment, suggests that the appropriateness of the routine hormonal treatment with gonadotrophin-releasing hormone analogues for 6-12 months, should be reconsidered and re-evaluated in further studies.

  8. Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy.

    Science.gov (United States)

    Novitzky, Dimitri; Mi, Zhibao; Collins, Joseph F; Cooper, David K C

    2015-01-01

    Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Gérald E. Piérard

    2013-01-01

    Full Text Available Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin.

  10. A role for central nervous growth hormone-releasing hormone signaling in the consolidation of declarative memories.

    Directory of Open Access Journals (Sweden)

    Manfred Hallschmid

    Full Text Available Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05. The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05. Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation.

  11. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    established in literature that stress signals such as psoriasis prompts the release of CRH from the hypothalamus paraventricular nucleus (PVN). CRH in turn triggers ACTH release from anterior pituitary [8] which ultimately controls the glucocorticoid discharge from adrenal cortex. Several of the glucocorticoids, which include ...

  12. Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone

    International Nuclear Information System (INIS)

    Folkers, K.; Bowers, C.Y.; Tang, P.L.; Kubota, M.

    1986-01-01

    Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known agonist analogs of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. The authors have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and they found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: [His 5 ,Trp 7 ,Gln 8 ]LHRH; [His 5 ,Trp 7 ,Leu 8 ]LHRH; [His 5 ,Trp 7 ]LHRH; [Trp 7 ]LHRH; [His 5 ]LHRH. These structures are a basis for the design of antagonists without Arg 8 toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of Arg 8 and Gln 8 or Leu 8 antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas. Radioreceptor assays and radioimmunoassays were utilized

  13. Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2014-01-01

    Full Text Available Hypoparathyroidism (HypoPT is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH. HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range. Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone.

  14. Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism.

    Science.gov (United States)

    Giustina, A; Ferrari, C; Bodini, C; Buffoli, M G; Legati, F; Schettino, M; Zuccato, F; Wehrenberg, W B

    1990-12-01

    In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

    Science.gov (United States)

    Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

    2012-03-01

    Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

  16. Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

    Directory of Open Access Journals (Sweden)

    Fuminori Sato

    2005-09-01

    Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

  17. Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    A. I. Neimark

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

  18. External radiation therapy of prostatic carcinoma and its relationship to hormonal therapy

    International Nuclear Information System (INIS)

    Takada, Chitose; Ito, Koushiro; Nishi, Junko; Yamamoto, Toshihiro; Hatanaka, Yoshimi; Baba, Yuji; Takahashi, Mutsumasa.

    1995-01-01

    From 1980 to 1990, a total of 54 patients with prostatic carcinoma were treated with external radiation therapy at the Kumamoto National Hospital. Ten patients were classified as Stage B, 22 as Stage C, and another 22 as Stage D according to the American Urological Association Clinical Staging System. The 5-year survival for all 54 patients was 30%. The 5-year disease-specific survival was 67% for Stage B, 47% for Stage C, and 26% for Stage D. The 5-year survival was 43% for patients in whom radiation therapy was initiated immediately after the first diagnosis or with less than one year of hormonal therapy, while it was 0% for patients in whom radiation therapy was initiated after more than one year of hormonal therapy (p=0.01). The cause of intercurrent death was acute myocardial infarction in four patients and acute cardiac failure in one. Four of these patients received hormonal therapy for more than one year. The incidence of radiation-induced proctitis was not severe. This study suggests that long-term hormonal therapy prior to radiation therapy worsens the prognosis of patients with prostatic carcinoma. (author)

  19. A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

    Science.gov (United States)

    Ludwig, Natasha G; Radaeli, Rafael F; Silva, Mariana M X; Romero, Camila M; Carrilho, Alexandre J F; Bessa, Danielle; Macedo, Delanie B; Oliveira, Maria L; Latronico, Ana Claudia; Mazzuco, Tânia L

    2016-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

  20. Gonadotropin-releasing hormone agonist trigger in oocyte donors co-treated with a gonadotropin-releasing hormone antagonist

    DEFF Research Database (Denmark)

    Vuong, T. N. L.; Ho, M. T.; Ha, T. D.

    2016-01-01

    -35 years, body mass index [BMI] hormone level >1.25 ng/mL, and antral follicle count >= 6). Intervention(s): Ovulation trigger with 0.2, 0.3, or 0.4 mg triptorelin in a GnRH antagonist cycle. Main Outcome Measure(s): The primary end point was number of metaphase II oocytes...... to number of metaphase II oocytes (16.0 +/- 8.5, 15.9 +/- 7.8, and 14.7 +/- 8.4, respectively), embryos (13.2 +/- 7.8, 11.7 +/- 6.9, 11.8 +/- 7.0), and number of top-quality embryos (3.8 +/- 2.9, 3.6 +/- 3.0, 4.1 +/- 3.0). Luteinizing hormone levels at 24 hours and 36 hours after trigger was significantly...

  1. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  2. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  3. Hormone therapy in transgender adults is safe with provider supervision; A review of hormone therapy sequelae for transgender individuals

    OpenAIRE

    Weinand, Jamie D.; Safer, Joshua D.

    2015-01-01

    Introduction: Some providers report concern for the safety of transgender hormone therapy (HT). Methods: This is a systematic literature review of HT safety for transgender adults. Results: Current literature suggests HT is safe when followed carefully for certain risks. The greatest health concern for HT in transgender women is venous thromboembolism. HT among transgender men appears to cause polycythemia. Both groups experienced elevated fasting glucose. There is no increase in cancer...

  4. Endurance exercise modulates levodopa induced growth hormone release in patients with Parkinson's disease.

    Science.gov (United States)

    Müller, Thomas; Welnic, Jacub; Woitalla, Dirk; Muhlack, Siegfried

    2007-07-11

    Acute levodopa (LD) application and exercise release human growth hormone (GH). An earlier trial showed, that combined stimulus of exercise and LD administration is the best provocative test for GH response in healthy participants. Objective was to show this combined effect of LD application and exercise on GH response and to investigate the impact on LD metabolism in 20 previously treated patients with Parkinson's disease (PD). We measured GH- and LD plasma concentrations following soluble 200 mg LD/50 mg benserazide administration during endurance exercise and rest on two separate consecutive days. GH concentrations significantly increased on both days, but GH release was significantly delayed during rest. LD metabolism was not altered due to exercise in a clinical relevant manner. Exercise induced a significant faster LD stimulated GH release in comparison with the rest condition. We did not find the supposed increase of LD induced GH release by endurance exercise. We assume, that only a limited amount of GH is available for GH release in the anterior pituitary following an acute 200 mg LD administration. GH disposal also depends on growth hormone releasing hormone (GHRH), which is secreted into hypothalamic portal capillaries. During the exercise condition, the resulting higher blood pressure supports blood flow and thus GHRH transport towards the GH producing cells in the pituitary. This might additionally have caused the significant faster GH release during exercise.

  5. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    International Nuclear Information System (INIS)

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10 5 /well). Cells treated with GnRH Ca ++ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca ++ -free media prevented the action of GnRH. GnRH caused a rapid efflux of 45 Ca ++ . Both GnRH-stimulated 45 Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect 45 Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE 2 and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca ++ does not regulate LH release; (2) GnRH elevates intracellular Ca ++ by opening both voltage sensitive and receptor mediated Ca ++ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release

  6. The effects of growht hormone therapy in children with radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Shalet, S.M.; Whitehead, E.; Chapman, A.J.; Beardwell, C.G.

    1981-01-01

    The effects of growth hormone (GH) therapy were studied in 6 children, previously treated for brain tumours which did not directly involve the hypothalamic-pituitary axis, and who had received cranial irradiation between 2.1 and 10 years earlier. All 6 were short with a standing height standard deviation score (SDS) from -1.7 to -3.3. Impaired growth hormone responses to an insulin tolerance test (ITT) were observed in all 6 and a Bovril stimulation test in 5 children. The remainder of pituitary function was essentially normal. All 6 were prepubertal and 5 had a retarded bone age. Subsequently all received human GH in a dose of 5 units 3 times weekly for 1 year. The growth rate in each was at least 2 cm greater during the treatment year than the pre-treatment year.(author)

  7. Fixed-functional appliance treatment combined with growth hormone therapy.

    Science.gov (United States)

    Jung, Min-Ho

    2017-09-01

    The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant. This case report demonstrates that the mandible grew significantly during fixed functional appliance treatment combined with GH therapy, with stable results during 2 years 11 months of retention. More studies are needed to evaluate GH therapy as a supplement in Class II treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  8. Primary prevention of cardiovascular disease with hormone replacement therapy

    DEFF Research Database (Denmark)

    Schierbeck, L

    2015-01-01

    Many peri- and postmenopausal women suffer from a reduced quality of life due to menopausal symptoms and preventable diseases. The importance of cardiovascular disease in women must be emphasized, as it is the leading cause of mortality and morbidity in women. It is well known that female hormones...... contribute to the later onset of cardiovascular disease in women. The effect of estrogens has for decades been understood from observational studies of postmenopausal women treated with hormone replacement therapy (HRT). Later, treatment with HRT was disregarded due to the fear of side......-effects and an ambiguity of the cardiovascular advantages. Accumulating knowledge from the large number of trials and studies has elucidated the cause for the disparity in results. In this paper, the beneficial effects of HRT, with emphasis on cardiovascular disease are explained, and the relative and absolute risks...

  9. Synthesis and release of luteinizing hormone in vitro: manipulations of Ca2+ environment

    International Nuclear Information System (INIS)

    Liu, T.C.; Jackson, G.L.

    1985-01-01

    The authors determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. They monitored LH synthesis when LH release was stimulated either by specific [gonadotropin-releasing hormone (GnRH)] or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of [ 3 H]glucosamine (glycosylation) and [ 14 C]alanine (translation) into total (cell and medium) immunoprecipitable LH by cultured rat anterior pituitary cells. Both GnRH (1 nM) and 50 mM K+ significantly stimulated LH release and glycosylation, but had no effect on LH translation. A23187 also stimulated LH release, but significantly depressed glycosylation of LH and total protein and [ 14 C]alanine uptake. Deletion of Ca2+ from the medium depressed both GnRH-induced LH release and glycosylation. Addition of 0.1 mM EGTA to Ca2+-free medium not only inhibited GnRH-induced release and glycosylation of LH but also uptake of precursors and glycosylation and translation of total protein. Thus, glycosylation and release of LH are Ca2+ dependent. Whether parallel changes in LH release and glycosylation reflect a cause and effect relationship remains to be determined

  10. The estrogen myth: potential use of gonadotropin-releasing hormone agonists for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Casadesus, Gemma; Garrett, Matthew R; Webber, Kate M; Hartzler, Anthony W; Atwood, Craig S; Perry, George; Bowen, Richard L; Smith, Mark A

    2006-01-01

    Estrogen and other sex hormones have received a great deal of attention for their speculative role in Alzheimer's disease (AD), but at present a direct connection between estrogen and the pathogenesis of AD remains elusive and somewhat contradictory. For example, on one hand there is a large body of evidence suggesting that estrogen is neuroprotective and improves cognition, and that hormone replacement therapy (HRT) at the onset of menopause reduces the risk of developing AD decades later. However, on the other hand, studies such as the Women's Health Initiative demonstrate that HRT initiated in elderly women increases the risk of dementia. While estrogen continues to be investigated, the disparity of findings involving HRT has led many researchers to examine other hormones of the hypothalamic-pituitary-gonadal axis such as luteinising hormone (LH) and follicle-stimulating hormone. In this review, we propose that LH, rather than estrogen, is the paramount player in the pathogenesis of AD. Notably, both men and women experience a 3- to 4-fold increase in LH with aging, and LH receptors are found throughout the brain following a regional pattern remarkably similar to those neuron populations affected in AD. With respect to disease, serum LH level is increased in women with AD relative to non-diseased controls, and levels of LH in the brain are also elevated in AD. Mechanistically, we propose that elevated levels of LH may be a fundamental instigator responsible for the aberrant reactivation of the cell cycle that is seen in AD. Based on these aforementioned aspects, clinical trials underway with leuprolide acetate, a gonadotropin-releasing hormone agonist that ablates serum LH levels, hold great promise as a ready means of treatment in individuals afflicted with AD.

  11. Hypothalamic growth hormone releasing factor deficiency following cranial irradiation

    International Nuclear Information System (INIS)

    Ahmed, S.R.; Shalet, S.M.

    1984-01-01

    The effect of synthetic human pancreatic tumour GH releasing factor (hp GRF1-44) on GH release has been studied in 10 patients with radiation-induced GH deficiency and four normal subjects. All 10 patients showed subnormal GH responses to both an ITT (median peak GH 3.2 mU/1) and to arginine stimulation (median peak GH 2.9 mU/1), although the remainder of pituitary function was intact. Following an acute intravenous bolus (100 μg) of hp GRF1-44, there was no GH response in two patients and a subnormal but definite GH response in a further four. The remaining four patients showed a significant GH response (median peak GH level 29 mU/1; range 22-57 mU/1) to hp GRF1-44, similar in magnitude and timing to that seen in th four normals. This strongly suggests that in these four subjects, the discrepancy in GH responses to hp GRF1-44, ITT and to arginine was a result of radiation-induced hypothalamic damage leading to a deficiency of endogenous GRF. The availability of synthetic hp GRF capable of stimulating GH secretion means that the distinction between hypothalamic and pituitary causes of GH deficiency will be of considerable therapeutic importance in the future. (author)

  12. Chitosan-based DNA delivery vector targeted to gonadotropin-releasing hormone (GnRH) receptor.

    Science.gov (United States)

    Boonthum, Chatwalee; Namdee, Katawut; Boonrungsiman, Suwimon; Chatdarong, Kaywalee; Saengkrit, Nattika; Sajomsang, Warayuth; Ponglowhapan, Suppawiwat; Yata, Teerapong

    2017-02-10

    The main purpose of this study was to investigate the application of modified chitosan as a potential vector for gene delivery to gonadotropin-releasing hormone receptor (GnRHR)-expressing cells. Such design of gene carrier could be useful in particular for gene therapy for cancers related to the reproductive system, gene disorders of sexual development, and contraception and fertility control. In this study, a decapeptide GnRH was successfully conjugated to chitosan (CS) as confirmed by proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The synthesized GnRH-conjugated chitosan (GnRH-CS) was able to condense DNA to form positively charged nanoparticles and specifically deliver plasmid DNA to targeted cells in both two-dimensional (2D) and three-dimensional (3D) cell cultures systems. Importantly, GnRH-CS exhibited higher transfection activity compared to unmodified CS. In conclusion, GnRH-conjugated chitosan can be a promising carrier for targeted DNA delivery to GnRHR-expressing cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin-releasing hormone neurons

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; van Heerikhuize, Joop; Swaab, Dick F.; Buijs, Ruud M.

    2002-01-01

    By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH)-producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control

  14. Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome

    NARCIS (Netherlands)

    Bayram, N.; van Wely, M.; van der Veen, F.

    2004-01-01

    BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in

  15. Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man

    DEFF Research Database (Denmark)

    Oturai, P S; Friberg, L; Sam, I

    1992-01-01

    emission computerized tomograph and inhalation of 133Xe. Thyrotropin-releasing hormone caused a significant mean increase of 3.7% (range -8.8-22.7) in blood flow in a region consistent with the left thalamus compared to placebo (3.2% decrease). In 25 other regions no significant change was detected...

  16. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles

    NARCIS (Netherlands)

    Youssef, Mohamed A. F. M.; van der Veen, Fulco; Al-Inany, Hesham G.; Griesinger, Georg; Mochtar, Monique H.; Aboulfoutouh, Ismail; Khattab, Sherif M.; van Wely, Madelon

    2011-01-01

    Background Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is

  17. Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals

    Science.gov (United States)

    Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in some mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, s...

  18. Emerging options in growth hormone therapy: an update

    Directory of Open Access Journals (Sweden)

    Kemp SF

    2011-08-01

    Full Text Available Stephen F Kemp, J Paul FrindikUniversity of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USAAbstract: Growth hormone (GH was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS, which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell–Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks.Keywords: growth hormone, somatotropin, anabolic, short stature

  19. Depression related to (neo)adjuvant hormonal therapy for prostate cancer

    International Nuclear Information System (INIS)

    Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

    2011-01-01

    Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

  20. Therapy of hypoparathyroidism by replacement with parathyroid hormone

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

    2014-01-01

    Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (Qo...... recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects...

  1. The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

    Science.gov (United States)

    Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

    1993-09-01

    In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

  2. Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

    Science.gov (United States)

    Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

    2012-03-01

    Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Hormone replacement therapy and the risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sjögren, Lea L; Mørch, Lina Steinrud; Løkkegaard, Ellen

    2016-01-01

    BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus...... progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only......, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone...

  4. Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75.

    Science.gov (United States)

    Bokser, L; Bajusz, S; Groot, K; Schally, A V

    1990-09-01

    Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl)-D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB-75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng/ml was observed, corresponding to the "burst" effect. Levels of the analog decreased to 19.6 ng/ml on day 2, gradually reached a concentration of 4.7 ng/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum

  5. Ontogenesis of neurons producing luteinizing hormone-releasing hormone (LHRH) in the nervus terminalis of the rat.

    Science.gov (United States)

    Schwanzel-Fukuda, M; Morrell, J I; Pfaff, D W

    1985-08-15

    Immunoreactive luteinizing hormone-releasing hormone (LHRH) was first detected at 15 days of gestation in ganglion cells associated with the peripheral, intracranial, and central parts of the nervus terminalis of the rat. LHRH was not detected in any other structure of the central nervous system at this age. In the 17-day-old fetal rat, 62% of the total LHRH-reactive neuronal population was found in ganglion cells of the nervus terminalis. At this same age, immunoreactive beta-luteinizing hormone (beta-LH) was first seen in gonadotropes of the anterior pituitary gland. At 19 days of gestation, 31% of the total number of LHRH-reactive neurons observed in the rat brain was found in the nervus terminalis, and immunoreactive processes were first seen in the organum vasculosum of the lamina terminalis and in the median eminence. Our data indicate that from 15 to 19 days of gestation the nervus terminalis is a principal source of LHRH in the fetal rat. Presence of the decapeptide in the nervus terminalis prior to appearance of beta-LH in the anterior pituitary suggests a possible role for LHRH in this system on maturation of the gonadotropes and differentiation of the brain-pituitary-gonadal axis.

  6. Hormonal therapy and risk of breast cancer in mexican women.

    Directory of Open Access Journals (Sweden)

    Amina Amadou

    Full Text Available The use of hormonal therapies, including hormonal contraceptives (HC and postmenopausal hormone replacement therapy (HRT have been shown to influence breast cancer (BC risk. However, the variations of these effects among populations and ethnic groups are not completely documented, especially among Hispanic women. We evaluated the association between HC and premenopausal BC risk, and between HRT and postmenopausal BC risk in Mexican women. Data from a Mexican multi-center population-based case-control study ofwomen aged 35 to 69 years were analysed. A total of 1000 cases and 1074 matched controls were recruited between 2004 and 2007. Information on hormonal therapy was collected through a structured questionnaire. Results were analysed using conditional logistic regression models. Overall, HC were used by 422/891 (47.3% premenopausal women and HRT was used by 220/1117 (19.7% postmenopausal women. For HC, odds ratios (ORs for BC were 1.11 (95% confidence interval (CI: 0.82, 1.49 for current users and 1.68 (95% CI: 0.67, 4.21 for ever-users. No clear effect of duration of use was observed. For HRT, the OR for BC was significantly increased in ever users (OR: 1.45; 95% CI: 1.01, 2.08. A non-significant increased risk was observed for combined estrogen/progestin, (OR =  1.85; 95% CI: 0.84, 4.07 whereas no effect was observed for the use of estrogen alone (OR = 1.14; 95% CI: 0.68, 1.91. Our results indicate that, HC had a non-significant effect on the risk of pre-menopausal BC, but suggested that injected contraceptives may slightly increase the risk, whereas HRT had a significant effect on post-menopausal BC in this population. This study provides new information about the effects of HC and HRT on BC risk in a Mexican population, which may be of relevance for the population of Latin America as a whole.

  7. Corticotropin-releasing hormone induces depression-like changes of sleep electroencephalogram in healthy women.

    Science.gov (United States)

    Schüssler, P; Kluge, M; Gamringer, W; Wetter, T C; Yassouridis, A; Uhr, M; Rupprecht, R; Steiger, A

    2016-12-01

    We reported previously that repetitive intravenous injections of corticotropin-releasing hormone (CRH) around sleep onset prompt depression-like changes in certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep during the second half of the night, blunted growth hormone peak, elevated cortisol concentration during the first half of the night). Furthermore a sexual dimorphism of the sleep-endocrine effects of the hormones growth hormone-releasing hormone and ghrelin was observed. In the present placebo-controlled study we investigated the effect of pulsatile administration of 4×50μg CRH on sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in young healthy women. After CRH compared to placebo, intermittent wakefulness increased during the total night and the sleep efficiency index decreased. During the first third of the night, REM sleep and stage 2 sleep increased and sleep stage 3 decreased. Cortisol concentration was elevated throughout the night and during the first and second third of the night. GH secretion remained unchanged. Our data suggest that after CRH some sleep and endocrine activity parameters show also depression-like changes in healthy women. These changes are more distinct in women than in men. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

    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

  9. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

    Science.gov (United States)

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

  10. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

    International Nuclear Information System (INIS)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

    1989-01-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel 6 ]LH-RH (SB-05) and [Ac-D-Nal(2) 1 ,D-Phe(pCl) 2 ,D-Pal(3) 3 ,Arg 5 ,D-Mel 6 ,D-Ala 10 ]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel 6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells

  11. Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

    Science.gov (United States)

    Werther, G A; Warne, G L; Ennis, G; Gold, H; Silink, M; Cowell, C T; Quigley, C; Howard, N; Antony, G; Byrne, G C

    1990-02-01

    A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

  12. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta

    International Nuclear Information System (INIS)

    Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A.

    1988-01-01

    Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery

  13. Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

    Directory of Open Access Journals (Sweden)

    Nicholas V. Vamvakopoulos

    1995-01-01

    Full Text Available This review higlghts key aspects of corticotropin releasing hormone (CRH biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h CRH gene: (1 a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic glucocorticoid administration in clinical practice and (2 a heuristic diagram to illustrate the proposed modulation of the stress response and immune/ inflammatory reaction by steroid hormones, from the perspective of the CRH system.

  14. Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

    Science.gov (United States)

    Steingold, K; De Ziegler, D; Cedars, M; Meldrum, D R; Lu, J K; Judd, H L; Chang, R J

    1987-10-01

    Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic Gn

  15. 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.

  16. Radiation therapy of newly diagnosed, advanced prostatic cancer and hormonally relapsed prostatic cancer

    International Nuclear Information System (INIS)

    Suzuki, Minoru; Fujiwara, Kazuhisa; Hayakawa, Katsumi; Hida, Shuichi

    1994-01-01

    Ten patients with newly diagnosed, advanced prostatic cancer were treated with radiotherapy and hormone therapy to improve tumor control and survival. Eight patients with hormonally relapsed prostatic cancer were treated with radiotherapy to improve their quality of life. Local control of the tumor was achieved in 9 of 10 patients with newly diagnosed, advanced prostatic cancer. Five of eight patients with hormonally relapsed prostatic cancer obtained improved quality of life. Combined radiotherapy and hormone therapy were effective in the treatment of newly diagnosed, advanced prostatic cancer, and radiotherapy was useful for improving the quality of life of patients with hormonally relapsed prostatic cancer. (author)

  17. Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E

    Science.gov (United States)

    Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam

    2011-01-01

    Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094

  18. Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

    Science.gov (United States)

    Elkind-Hirsch, K E; Anania, C; Malinak, R

    1996-09-01

    To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

  19. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  20. Consensus statement on the use of gonadotropin-releasing hormone analogs in children

    DEFF Research Database (Denmark)

    Carel, Jean-Claude; Eugster, Erica A; Rogol, Alan

    2009-01-01

    , an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. EVIDENCE: Preference was given to articles written in English with long-term outcome data. The US Public Health grading system was used to grade evidence and rate the strength of conclusions. When evidence......OBJECTIVE: Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society...... for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe...

  1. Menopause and postmenopausal hormone therapy and risk of hearing loss.

    Science.gov (United States)

    Curhan, Sharon G; Eliassen, A Heather; Eavey, Roland D; Wang, Molin; Lin, Brian M; Curhan, Gary C

    2017-09-01

    Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss. Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss. After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.

  2. Care of the cancer survivor: metabolic syndrome following hormone-modifying therapy

    OpenAIRE

    Redig, Amanda J.; Munshi, Hidayatullah G.

    2010-01-01

    Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies may increase patients’ risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones, thus treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardi...

  3. Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Nanda, Akash; Chen, M.-H.; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2010-01-01

    Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score ≥8, or clinical category ≥T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

  4. Inhibition of growth of experimental prostate cancer with sustained delivery systems (microcapsules and microgranules) of the luteinizing hormone-releasing hormone antagonist SB-75.

    Science.gov (United States)

    Korkut, E; Bokser, L; Comaru-Schally, A M; Groot, K; Schally, A V

    1991-02-01

    Inhibitory effects of the sustained delivery systems (microcapsules and microgranules) of a potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1, 4-chloro-D-phenylalanine2, 3-(3-pyridyl)-D-alanine3, D-citrulline6, D-alanine10]LH-RH (SB-75) on the growth of experimental prostate cancers were investigated. In the first experiment, three doses of a microcapsule preparation releasing 23.8, 47.6, and 71.4 micrograms of antagonist SB-75 per day were compared with microcapsules of agonist [D-Trp6]LH-RH liberating 25 micrograms/day in rats bearing Dunning R3327H transplantable prostate carcinoma. During 8 weeks of treatment, tumor growth was decreased by [D-Trp6]LH-RH and all three doses of SB-75 as compared to untreated controls. The highest dose of SB-75 (71.4 micrograms/day) caused a greater inhibition of prostate cancer growth than [D-Trp6]LH-RH as based on measurement of tumor volume and percentage change in tumor volume. Doses of 23.8 and 47.6 micrograms of SB-75 per day induced a partial and submaximal decrease, respectively, in tumor weight and volume. Tumor doubling time was the longest (50 days) with the high dose of SB-75 vs. 15 days for controls. The body weights were unchanged. The weights of testes, seminal vesicles, and ventral prostate were greatly reduced in all three groups that received SB-75, and testosterone levels were decreased to nondetectable values in the case of the two higher doses of SB-75. LH levels were also diminished. Similar results were obtained in the second experiment, in which the animals were treated for a period of 8 weeks with microgranules of SB-75. Therapy with microgranules of SB-75 significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The results indicate that antagonist SB-75, released from sustained delivery systems, can produce a state of chemical castration and effectively

  5. Development of a radioimmunoassay for circulating levels of gonadotropin releasing hormone

    International Nuclear Information System (INIS)

    Moodbidri, S.B.; Joshi, L.R.; Sheth, A.R.; Rao, S.S.

    1976-01-01

    A specific and sensitive radioimmunoassay system has been developed for measuring gonadotropin releasing hormone (GnRH) in unextracted human serum. Circulating levels of GnRH, LH and FSH were determined in 37 serum samples obtained from twenty normal healthy women on different days of the menstrual cycle. GnRH and LH but not FSH exhibited similar patterns during the menstrual cycle. 125 I-labelled GnRH was used in the RIA system. (author)

  6. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus

    OpenAIRE

    Jeanneteau, Freddy D.; Lambert, W. Marcus; Ismaili, Naima; Bath, Kevin G.; Lee, Francis S.; Garabedian, Michael J.; Chao, Moses V.

    2012-01-01

    Regulation of the hypothalamic–pituitary–adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased ...

  7. Corticotropine-releasing hormone and/or corticosterone differentially affect behavior of rat

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Řezáčová, Lenka; Stuchlík, Aleš

    2008-01-01

    Roč. 11, Suppl.1 (2008), s. 118-118 ISSN 1461-1457. [CINP Congress /26./. 13.07.2008-17.07.2008, Munich] R&D Projects: GA MŠk(CZ) 1M0517; GA MZd NR9180; GA ČR(CZ) GA309/07/0341 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * corticotropine-releasing hormone * corticosterone * behavior Subject RIV: FH - Neurology

  8. Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

    OpenAIRE

    Vamvakopoulos, Nicholas V.

    1995-01-01

    This review higlghts key aspects of corticotropin releasing hormone (CRH) biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h) CRH gene: (1) a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic gl...

  9. Characterization of brn1.2 and corticotropin-releasing hormone genes in zebrafish

    OpenAIRE

    Chandrasekar, Gayathri

    2007-01-01

    The zebrafish (Danio rerio), a tropical fresh water fish originally found in the rivers of India and Bangladesh has become a popular vertebrate model system over the last decade. The rapid sequencing of the zebrafish genome together with the latest advances in forward and reverse genetics has made this model organism more fascinating as it can be used to decipher the genetic mechanisms involved in the vertebrate development. Corticotropin-releasing hormone (CRH) regulates t...

  10. Gonadotrophin-Releasing Hormone Agonists and Other Contraceptive Medications in Exotic Companion Animals.

    Science.gov (United States)

    Schoemaker, Nico J

    2018-05-01

    The use of a gonadotrophin-releasing hormone agonist slow-release implant (GnRH A-SRI) has become increasingly popular as an alternative for surgical contraception in many species. Although these implants have proven to be very effective in some species (eg, ferrets, rats, chicken, psittacines, and iguanas), they have been found less effective in other species (eg, male guinea pigs and rabbits, veiled chameleons, slider turtles, and leopard geckos). This review provides an overview of the available literature on the effects of GnRH A-SRIs in companion exotic animals. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Intermittent hormonal therapy in the treatment of post-irradiation residual/recurrent prostate cancer

    International Nuclear Information System (INIS)

    Williams, Aaron O; Kocherill, Paul G; Wallace, Michelle; Forman, Jeffrey D

    1996-01-01

    Purpose: To evaluate the efficacy and toxicity of intermittent hormonal therapy in the treatment of residual/recurrent prostate cancer. Materials and Methods: Seventeen patients with biochemical evidence of residual/recurrent prostate cancer were initially treated with radiation therapy (RT)(13), neo-adjuvant hormonal therapy and RT (3), or RT following prostatectomy (1). The mean follow-up time was 19.4 months from the initiation of hormonal therapy. Hormonal therapy consisted of an LH-RH agonist alone (7), an anti-androgen alone (1) or a combination of both (9). Hormonal therapy was continued until the prostatic specific antigen (PSA) level became undetectable. IHT was reinstituted when the PSA reached a pre-determined level, usually greater than or equal to 10ng/ml. Results: The mean time from completion of primary treatment to the initiation of hormonal therapy was 32.5 months. The mean PSA at the start of the first cycle of hormonal therapy was 43.9ng/ml, the second cycle, 11.9ng/ml and the third cycle, 24ng/ml. The mean PSA levels at the end of the first and second cycle of hormonal therapy were .48 and .42ng/ml, respectively. No patient has yet completed the third cycle of hormonal therapy. The average duration of hormonal therapy was 10 months for the first cycle and 4 months for the second cycle. The mean intermittent time off hormones were 9.3 months between cycles 1 and 2, and 10 months between cycles 2 and 3. No patient has yet become refractory to hormonal therapy. Currently all patients are alive. All patients experienced hot flashes and decreased libido at varying degrees during treatment. Thirty-five percent experienced gynecomastia. During the intervals between hormonal therapy, most patients reported a decrease in hot flashes. Conclusion: This analysis supplies preliminary evidence that intermittent hormonal therapy is a viable option in patients with biochemical evidence of disease following initial therapy. It is associated with less treatment

  12. Hormone therapy and cardiovascular risk markers and disease

    DEFF Research Database (Denmark)

    Pedersen, Susan H; Lokkegaard, Ellen; Ottesen, Bent

    2006-01-01

    therapy (HT), although an underlying healthy-user effect may account for these observations. Progestagens are added to protect against an increased risk of endometrial cancer observed with unopposed estrogen treatment. The inclusion of progestagen in HT has been associated with possible adverse......Biological studies have demonstrated estrogen's beneficial effect on cardiovascular risk factors, including plasma lipoproteins, atherogenesis, vascular reactivity, inflammation and antioxidative activity. Additionally, observational studies have supported a cardioprotective effect of hormone...... cardiovascular outcomes. Recent, large-scale, randomized clinical studies did not confirm a beneficial cardiovascular effect of HT. On the contrary, an increased risk was found with continuous combined estrogen-progestagen regimens. The progestagen used in these trials was medroxyprogesterone acetate and other...

  13. Growth hormone therapy and craniofacial bones: a comprehensive review.

    Science.gov (United States)

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a.

    Science.gov (United States)

    Casanueva, Felipe F; Camiña, Jesus P; Carreira, Marcos C; Pazos, Yolanda; Varga, Jozsef L; Schally, Andrew V

    2008-12-23

    Ghrelin synergizes with growth hormone-releasing hormone (GHRH) to potentiate growth hormone (GH) response through a mechanism not yet fully characterized. This study was conducted to analyze the role of GHRH as a potential ligand of the ghrelin receptor, GHS-R1a. The results show that hGHRH(1-29)NH(2) (GHRH) induces a dose-dependent calcium mobilization in HEK 293 cells stably transfected with GHS-R1a an effect not observed in wild-type HEK 293 cells. This calcium rise is also observed using the GHRH receptor agonists JI-34 and JI-36. Radioligand binding and cross-linking studies revealed that calcium response to GHRH is mediated by the ghrelin receptor GHS-R1a. GHRH activates the signaling route of inositol phosphate and potentiates the maximal response to ghrelin measured in inositol phosphate turnover. The presence of GHRH increases the binding capacity of (125)I-ghrelin in a dose dependent-fashion showing a positive binding cooperativity. In addition, confocal microscopy in CHO cells transfected with GHS-R1a tagged with enhanced green fluorescent protein shows that GHRH activates the GHS-R1a endocytosis. Furthermore, the selective GHRH-R antagonists, JV-1-42 and JMR-132, act also as antagonists of the ghrelin receptor GHS-R1a. Our findings suggest that GHRH interacts with ghrelin receptor GHS-R1a, and, in consequence, modifies the ghrelin-associated intracellular signaling pathway. This interaction may represent a form of regulation, which could play a putative role in the physiology of GH regulation and appetite control.

  15. Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

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    Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

    1996-03-29

    Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

  16. Structural and functional divergence of growth hormone-releasing hormone receptors in early sarcopterygians: lungfish and Xenopus.

    Directory of Open Access Journals (Sweden)

    Janice K V Tam

    Full Text Available The evolutionary trajectories of growth hormone-releasing hormone (GHRH receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR(2 in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP receptor (PRPR. In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR(2 in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR(2 was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR(2 had the highest expression in brain, and interestingly, X. laevis(GHRHR2 also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR(2, which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP.

  17. Terapia hormonal y calidad del hueso Hormone therapy and bone quality

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available La osteoporosis se reconoce como uno de los problemas de salud de la población femenina posmenopáusica, y la terapia hormonal de reemplazo (THR como una de las medidas terapéuticas efectivas para evitar la fractura. Nos propusimos mostrar la experiencia acumulada en relación con el efecto de la terapia hormonal de reemplazo sobre la calidad del hueso. En un estudio retrospectivo realizado en 42 mujeres con edades entre 40 y 59 años que asistieron a la Clínica de Climaterio y Osteoporosis y a la consulta multidisciplinaria de climaterio del Hospital Ginecoobstétrico “Ramón González Coro” entre enero de 1997 y diciembre del año 2003, se determinó la calidad ósea mediante absorciometría dual de rayos X en región lumbar (L2-L4 o por ultrasonido del calcáneo (USCAL y recibieron tratamiento continuado con terapia estrogénica (E o con estrógenos progestagenos (EP durante no menos de un año (n = 30. Las mujeres que no pudieron recibir THR fueron agrupadas y evaluadas como grupo control (n =12. Durante el tiempo de observación promedio de 2 años, las mujeres que recibieron THR mejoraron su calidad ósea en el 16,8 %, mientras que las del grupo control empeoraron en el 8 % de los casos. Estos resultados iniciales, aunque son modestos, muestran la utilidad de la THR para mejorar la calidad del hueso y la necesidad de continuar estudios que permitan definir en nuestro medio la persistencia de la mejoría ósea, así como la magnitud de la osteoporosis posmenopáusica.Osteoporosis is recognized as one of the health problems of the female postmenopausic population and the replacement hormone therapy (RHT as one of the effective therapeutical measures to prevent fracture. We proposed ourselves to show the experience accumulated in relation to the effect of the replacement hormone therapy on the bone quality. In a retrospective study conducted among 42 women aged 30-59 that attended the Climacteric and Osteoporosis Clinic and the

  18. In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case

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    Ceyda Tunakan Dalgıç

    2018-01-01

    Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

  19. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

    Science.gov (United States)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  20. Evaluation of in vivo [corrected] biological activity of new agmatine analogs of growth hormone-releasing hormone (GH-RH)

    Science.gov (United States)

    Bokser, L; Zarandi, M; Schally, A V

    1990-01-01

    The effects of agmatine analogs of growth hormone releasing hormone (GH-RH) were compared to GH-RH(1-29)-NH2 after intravenous (iv) and subcutaneous (sc) administration to pentobarbital-anesthetized male rats. After the iv injection, the analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-51); [desNH2-Tyr1,D-Lys12,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-57); [desNH2-Tyr1,Ala15,D-Lys21,Nle27] GH-RH(1-28)Agm (MZ-2-75) and [desNH2-Tyr1, D-Lys12,21, Ala15, Nle27] GH-RH(1-28)Agm (MZ-2-87) showed a potency equivalent to 4.4, 1.9, 1.07 and 1.03 times that of GH-RH (1-29)-NH2, respectively, at 5 min and 5.6, 1.8, 1.9 and 1.8 times higher, respectively, at 15 min. After sc administration, analogs MZ-2-51, MZ-2-57 and MZ-2-75 showed to be 34.3, 14.3 and 10.5 times more potent than the parent hormone at 15 min and 179.1, 88.9 and 45.0 times more active, respectively, at 30 min. In addition, MZ-2-51 had prolonged GH-releasing activity as compared to the standard. We also compared the activity of MZ-2-51 and MZ-2-57 with their homologous L-Arg and D-Arg analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-29)-NH2 (MZ-2-117), [des-NH2Tyr1,D-Lys12, Ala15, Nle27] GH-RH(1-29)NH2 (MZ-2-123) and [desNH2-Tyr1,D-Lys12,Ala15, Nle27,D-Arg29] GH-RH(1-29)NH2 (MZ-2-135) after intramuscular (im) injection. MZ-2-51 induced a somewhat greater GH release than MZ-2-117 at 15 min, both responses being larger than the controls (p less than 0.01) at 15 and 30 min. MZ-2-57, MZ-2-123 and MZ-2-135 given i.m. were able to stimulate GH release only at 15 minutes (p less than 0.05). Animals injected i.m. with MZ-2-51, but not with MZ-2-117, showed GH levels significantly higher than the control group (p less than 0.05) at 60 min. GH-RH(1-29)NH2 had low activity intramuscularly when tested at a dose of 2.5 micrograms. No toxic effects were observed after the iv administration of 1 mg/kg of Agm GH-RH analogs. These results indicate that our Agm analogs are active iv, sc and im and that the substitutions made in these

  1. Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    International Nuclear Information System (INIS)

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O'Connell, G.; Belbeck, L.

    1987-01-01

    To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance

  2. Effect of hormone therapy on postural balance in postmenopausal women.

    Science.gov (United States)

    Rodrigues Barral, Ana Beatriz Cesar; Nahas, Eliana Aguiar Petri; Nahas-Neto, Jorge; Cangussu, Luciana Mendes; Buttros, Davi de Araujo

    2012-07-01

    The aim of this study was to analyze the effects of hormone therapy (HT) on postural balance in postmenopausal women and its association with risk of falls. In this cross-sectional study, a total of 225 Brazilian postmenopausal women aged 45 to 75 years were included and divided into two groups: HT users (n = 102) and nonusers (n = 123). HT users were women who had continuously taken HT throughout the preceding 6 months, whereas nonusers received no such therapy during the same period. Women with amenorrhea for more than 12 months and aged 45 years or older were included. Those with neurological or musculoskeletal disorders, vestibulopathies, uncorrected visual deficit, or drug use that could affect balance were excluded. Histories of falls (previous 24 mo) as well as clinical and anthropometric characteristics were analyzed. Postural balance was assessed through stabilometry (computerized force platform), Romberg test, and crouching test. Statistical analysis included the median test, χ test, Spearman correlation coefficient, and logistic regression method (odds ratio). Women users of HT were younger (53.0 vs 57.0 y) and with a shorter time since menopause (5.5 vs 10.0 y) than nonusers (P Romberg test and fall rate (P > 0.05). In the crouching test, 47.1% of the participants showed an adequate level of muscle strength in lower limbs without differences between the groups (P > 0.05). Postmenopausal women using HT showed lower frequency of falls and a better performance in stabilometric parameters than did nonusers.

  3. Systematic review of hormone replacement therapy in the infertile man

    Directory of Open Access Journals (Sweden)

    Amr El Meliegy

    2018-03-01

    Full Text Available Objectives: To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve their fertility potential, as testosterone replacement therapy (TRT inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age. Materials and methods: We performed a comprehensive literature review for the years 1978–2017 via PubMed. Also abstracts from major urological/surgical conferences were reviewed. Review was consistent with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA criteria. We used Medical Subject Heading terms for the search including ‘testosterone replacement therapy’ or ‘TRT’ and ‘male infertility’. Results: In all, 91 manuscripts were screened and the final number used for the review was 56. All studies included were performed in adults, were written in English and had an abstract available. Conclusions: Exogenous testosterone inhibits spermatogenesis. Hypogonadal men wanting to preserve their fertility and at the same time benefiting from TRT effects can be prescribed selective oestrogen receptor modulators or testosterone plus low-dose human chorionic gonadotrophin (hCG. Patients treated for infertility with hypogonadotrophic hypogonadism can be prescribed hCG alone at first followed by or in combination from the start with follicle-stimulating hormone preparations. Keywords: Gonadotrophins, Hypogonadism, Infertility, Systematic review, Testosterone therapy

  4. Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.

    Science.gov (United States)

    Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

    2016-08-03

    Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

  5. Simultaneous measurement of hormone release and secretagogue binding by individual pituitary cells

    International Nuclear Information System (INIS)

    Smith, P.F.; Neill, J.D.

    1987-01-01

    The quantitative relationship between receptor binding and hormone secretion at the single-cell level was investigated in the present study by combining a reverse hemolytic plaque assay for measurement of luteinizing hormone (LH) secretion from individual pituitary cells with an autoradiographic assay of 125 I-labeled gonadontropin-releasing hormone (GnRH) agonist binding to the same cells. In the plaque assay, LH secretion induces complement-mediated lysis of the LH-antibody-coated erythrocytes around the gonadotropes, resulting in areas of lysis (plaques). LH release from individual gonadotropes was quantified by comparing radioimmunoassayable LH release to hemolytic area in similarly treated cohort groups of cells; plaque area was linearly related to the amount of LH secreted. Receptor autoradiography was performed using 125 I-labeled GnRH-A (a superagonist analog of GnRH) both as the ligand and as the stimulant for LH release in the plaque assay. The grains appeared to represent specific and high-affinity receptors for GnRH because (i) no pituitary cells other than gonadotropes bound the labeled ligand and (ii) grain development was progressively inhibited by coincubation with increasing doses of unlabeled GnRH-A. The authors conclude that GnRH receptor number for any individual gonadotrope is a weak determinant of the amount of LH it can secrete; nevertheless, full occupancy of all its GnRH receptors is required for any gonadotrope to reach its full LH-secretory capacity. Apparently the levels of other factors comprising the steps along the secretory pathway determine the secretory capacity of an individual cell

  6. Inhibition of rat pituitary growth hormone (GH) release by subclinical levels of lead

    International Nuclear Information System (INIS)

    Camoratto, A.M.; White, L.M.; Lau, Y.S.; Moriarty, C.M.

    1990-01-01

    Lead toxicity has been associated with short stature in children. Since growth hormone is a major regulator of growth, the effects of chronic exposure to subclinical lead levels on pituitary function were assessed. Timed pregnant rats were given 125 ppm lead (as lead nitrate) in their drinking water beginning on day 5 of gestation. After weaning, pups were continued on lead until sacrifice at 7 weeks of age. The average blood lead level at this time was 18.9 ug/dl (range 13.7-27.8). On the day of sacrifice the pituitary was removed, hemisected and incubated with vehicle or 40 nM hGRH (human growth hormone releasing hormone). Pituitaries from chronically lead-treated pups were 64% less responsive to GRH than controls. In contrast, no difference in responsiveness was observed in pituitaries from the dams. The specific binding of GRH was also examined. Control animals showed a dose-dependent displacement of 125I-GRH by unlabeled ligand (10-1000 nM). In the pituitaries of lead-treated pups binding of labeled ligand was markedly reduced by unlabeled GRH (less than 100 nM). Chronic exposure to lead had no effect on serum GH or prolactin levels or on pituitary content of GH. These data suggest that one mechanism by which lead can affect growth is by inhibition of GH release

  7. Neurokinin B and serum albumin limit copper binding to mammalian gonadotropin releasing hormone.

    Science.gov (United States)

    Gul, Ahmad Samir; Tran, Kevin K; Jones, Christopher E

    2018-02-26

    Gonadotropin releasing hormone (GnRH) triggers secretion of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary gland. GnRH is able to bind copper, and both in vitro and in vivo studies have suggested that the copper-GnRH complex is more potent at triggering gonadotropin release than GnRH alone. However, it remains unclear whether copper-GnRH is the active species in vivo. To explore this we have estimated the GnRH-copper affinity and have examined whether GnRH remains copper-bound in the presence of serum albumin and the neuropeptide neurokinin B, both copper-binding proteins that GnRH will encounter in vivo. We show that GnRH has a copper dissociation constant of ∼0.9 × 10 -9  M, however serum albumin and neurokinin B can extract metal from the copper-GnRH complex. It is therefore unlikely that a copper-GnRH complex will survive transit through the pituitary portal circulation and that any effect of copper must occur outside the bloodstream in the absence of neurokinin B. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain

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    Ribeiro Ana C

    2009-04-01

    Full Text Available Abstract Background Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36. Results Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH, and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36. Conclusion Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.

  9. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone

    Directory of Open Access Journals (Sweden)

    Mo Kyung Jung

    2014-12-01

    Full Text Available PurposeThere is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa in central precocious puberty (CPP. We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH in girls with CPP.MethodsWe reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS for bone age (BA, and compared adult height (AH with midparental height (MPH and predicted adult height (PAH during treatment in groups received GnRHa alone (n=59 or GnRHa plus GH (n=23.ResultsIn the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm was significantly higher than the initial PAH (156.6±3.96 cm (P<0.001, and it was similar to the MPH (159.9±3.52 cm. In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm was also higher than the initial PAH (154.6±2.55 cm (P<0.001, which was similar to the MPH (158.1±3.31 cm. Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment.ConclusionIn CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

  10. Antiproliferative effect of growth hormone-releasing hormone (GHRH antagonist on ovarian cancer cells through the EGFR-Akt pathway

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    Varga Jozsef

    2010-05-01

    Full Text Available Abstract Background Antagonists of growth hormone-releasing hormone (GHRH are being developed for the treatment of various human cancers. Methods MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR level and the phosphorylation of Akt (p-Akt, suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.

  11. Effects of an Antagonistic Analog of Growth Hormone-Releasing Hormone on Endometriosis in a Mouse Model and In Vitro.

    Science.gov (United States)

    Köster, Frank; Jin, Li; Shen, Yuanming; Schally, Andrew V; Cai, Ren-Zhi; Block, Norman L; Hornung, Daniela; Marschner, Gabriele; Rody, Achim; Engel, Jörg B; Finas, Dominique

    2017-11-01

    Endometriosis is a benign gynecologic disorder causing dysmenorrhea, pelvic pain, and subfertility. Receptors for the growth hormone-releasing hormone (GHRH) were found in endometriotic tissues. Antagonists of GHRH have been used to inhibit the growth of endometriotic endometrial stromal cells. In this study, the GHRH receptor splice variant (SV) 1 was detected in human endometrial tissue samples by Western blots and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The highest messenger RNA (mRNA) and protein levels of SV1 were found in eutopic endometrium from patients with endometriosis compared to ectopic endometriotic tissues and endometrium from normal patients. The highest expression for GHRH mRNA was found by qRT-PCR in ectopic endometriosis lesions. In an in vivo mouse model with human endometrial explants from patients with endometriosis, 10 μg MIA-602 per day resulted in significantly smaller human endometrial xenotransplants after 4 weeks compared to mice treated with vehicle. The endometrial tissues expressed SV1 before and after xenotransplantation. The proliferation of endometrial stromal cells as well as the endometriosis cell lines 12-Z and 49-Z was decreased by exposure to 1 μM MIA-602 after 72 hours. The protein levels of epithelial growth factor receptors in 12-Z and 49-Z cell lines were reduced 48 and 72 hours after the administration of 1 μM MIA-602. MIA-602 decreased the activation of the MAP-kinases ERK-1/2. Our study demonstrates the presence of SV1 receptor as a target for treatment with GHRH antagonist in endometriosis. Endometrial tissues respond to MIA-602 with inhibition of proliferation in vitro and in vivo. The use of MIA-602 could be an effective supplement to the treatment strategies in endometriosis.

  12. Radioimmunological studies of the thyrotropic function of the hypophysis under the effect of the thyrotropin-releasing hormone in thyroid diseases

    International Nuclear Information System (INIS)

    Vakulenko, A.D.; Matveenko, E.G.; Simakova, G.M.; Sorokina, V.G.; Golubnichaya, L.P.; Dobrova, G.S.

    1979-01-01

    The synthetic thyrotropin-releasing-hormone was stream-injected intravenously to 124 patients and 16 healthy people in doses of 200 μg. It was tolerated satisfactorily at the first and repeated injections. The radioimmunologic method was used prior to the test and 30 min after it to examine thyrotropin content in blood. In normal state the stimulation would result in 3.5-fold increase in thyrotropin level on the average. The hypophysial reserve of thyrotropin was significantly lower in cases of diffuse toxic goiter in grave and semigrave forms and toxic adenoma. It was significantly higher at primary hypothyrosis and retained at nodular euthyroid goiter, neupocirculatopy dystonia and mild thyrotoxicosis. At thyroid gland disturbances the test with thyrotropin-releasing-hormone is of diagnostic value at primary hypothyrosis in the initial latent period; besides, it can be used for control of substitution therapy and as a supplementary test at thyrotoxicosis

  13. [The changes of ghrelin, growth hormone, growth hormone releasing hormone and their clinical significances in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Xu, Zhi-song; Bao, Zi-yu; Wang, Zhi-ying; Yang, Guo-jun; Zhu, Dong-fang; Zhang, Li; Tan, Rong-mei

    2012-07-01

    To investigate the changes of plasma ghrelin, growth hormone (GH) and growth hormone releasing hormone (GHRH) and gastric ghrelin in patients with chronic obstructive pulmonary disease (COPD) and to explore their clinical significances. Plasma ghrelin, GH, GHRH, TNFα, IL-6 and C reactive protein (CRP) were measured in 40 COPD patients and 20 controls with chronic bronchitis. Correlated factors of plasma ghrelin, TNFα, IL-6, CRP were analyzed. Body composition was assessed with bioelectrical impedance analysis. The expression of gastric ghrelin in patients with COPD was detected. Plasma ghrelin was higher in the underweight patients than in the normal weight patients and in the controls [(1.78 ± 0.46) ng/L, (1.39 ± 0.46) ng/L, (1.36 ± 0.39) ng/L, respectively]. Plasma GH was lower in the underweight patients than in the normal weight patients and in the controls [(4.12 ± 0.83) µg/L, (5.17 ± 0.72)µg/L, (6.49 ± 1.13) µg/L, respectively]. Plasma GHRH was lower in the underweight patients than in the normal weight patients and in the controls [(20.43 ± 4.41) ng/L, (23.47 ± 3.97) ng/L, (27.48 ± 10.06) ng/L, respectively]. Plasma ghrelin was higher in the underweight patients than in the controls (P 0.05). Plasma ghrelin was positively correlated with TNFα and IL-6 in the underweight patients. The gastric expression of ghrelin showed no evident difference between the patients with COPD and the controls. The plasma GH in COPD patients may not be correlated with ghrelin. The plasma ghrelin level may be a useful indicator for malnutrition in COPD patients. Plasma ghrelin might be involved in the pathogenesis of CODP by affecting the body energy metabolism.

  14. Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Ja Hye Kim

    2014-03-01

    Full Text Available PurposeGrowth hormone (GH plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD. This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters.MethodsA total of 45 patients (17 females and 28 males diagnosed with childhood-onset GHD (CO-GHD were investigated and all patients had organic brain lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age 20.4±5.0 years (18.0-32.1 years. Recombinant human GH was administered at a dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height, body mass index (BMI, serum insulin-like growth factor 1 (IGF-1, serum total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, and triglyceride levels, were compared between baseline and 12 months after treatment using paired t-test. In addition, correlation between GH interruption period and clinical parameters including BMI, lipid profile, IGF-1, and IGFBP-3, was analyzed.ResultsOf 45 patients, 33 patients had GH interruption period of 4.3±3.6 years (0.7-12.5 years. Serum HDL-cholesterol level increased significantly, whereas LDL-cholesterol decreased after 1 year of GH replacement therapy. However, body weight and BMI showed no significant changes after 1 year of GH replacement therapy. There were no significant correlations between GH interruption period and lipid profile or anthropometric parameters.ConclusionBMI and body weight were not affected by GH replacement. However, GH replacement in adults with GHD offers benefits in lipid metabolism.

  15. Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

    Science.gov (United States)

    Casanueva, F F; Micic, D; Pombo, M; Leal, A; Bokser, L; Zugaza, J L; Dieguez, C

    1996-08-01

    Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

  16. Hormonal therapy with external radiation therapy for metastatic spinal cord compression from newly diagnosed prostate cancer

    International Nuclear Information System (INIS)

    Kato, So; Hozumi, Takahiro; Yamakawa, Kiyofumi; Higashikawa, Akiro; Goto, Takahiro; Shinohara, Mitsuru; Kondo, Taiji

    2013-01-01

    Although hormonal therapy is effective for treatment of prostate cancer, its effect in the treatment of metastatic spinal cord compression (MSCC) has not been established. The objective of this study was to clarify the efficacy of conservative treatment of MSCC-induced paralysis resulting from prostate cancer for patients without a previous treatment history. We reviewed data from 38 patients with MSCC-induced paralysis from newly diagnosed prostate cancer who presented to our service between 1984 and 2010. Conservative treatment consisted of hormonal therapy with external radiation therapy (ERT). Patient demographic data, treatment details, involved spine MRI images, complications, and the course of neurologic recovery were investigated. Twenty-five patients were treated conservatively. Mean follow-up period was 36.8 months. Sixteen patients (two with Frankel B, 14 with Frankel C) were unable to walk at initial presentation. After initiating conservative treatment, 75% (12 of 16) of these patients regained the ability to walk within 1 month, 88% (14 in 16) did so within 3 months, and all non-ambulatory patients did so within 6 months. No one had morbid complications. Four patients who did not regain the ability to walk at 1 month were found to have progressed to paraplegia rapidly, and tended to have severe compression as visualized on MRI, with a delay in the start of treatment in comparison with those who did so within 1 month (21.0 vs. 7.8 days). Hormonal therapy associated with ERT is an important option for treatment of MSCC resulting from newly diagnosed prostate cancer. (author)

  17. 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, ...

  18. Combined radio- and hormone therapy of the prostate carcinoma

    International Nuclear Information System (INIS)

    Papic, R.

    1979-08-01

    Intention of this study is to detect in 49 patients suffering from prostate carcinomas, effects and side effects of radiotherapy. According to the present results, there is not any doubt that prostate carcinomas are radiosensitive. In all patients radiotherapy induced a prostate shrinkage and an increasing of consistency. It resulted that a prostate biopsy must be carried out in order to control the success of therapy. The success of the treatment depends upon tumour spreading and on its degree of differentiation. Within the observation period only in four cases metastasation of the prostate carcinoma occurred after radiotherapy. According to literature, the 5-year survival rate with an organ-defined prostate carcinoma ranges between 70 and 80% when radiotherapeutic methods are applied. The same authors indicate a 5-year survival rate between 42 and 48% for scattered carcinomas. Only minor side effects are provoked by radiotherapy. In 75% of the patients pollakisuria and dysuria resulted. After irradiation was finished, the symptoms disappeared and did not cause in any case any late complications. In 12% of the cases proctitic pain occurred during irradiation, which in 6% remained even after the treatment was terminated. We could prove unequivocally on our patients that passage impairments caused by a prostate carcinoma are improved by radiotherapy. Finally it can be said that this treatment is applicable for curing carcinoma which is localised on the prostate. In the case of an undefined, scattered carcinoma radiotherapy combined with hormone therapy is the treatment of choice. With regards to undesired side effects radiotherapy is superior to other therapeutic measures. (orig./MG) [de

  19. Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone

    International Nuclear Information System (INIS)

    Huseman, C.A.; Moriarty, C.M.; Angle, C.R.

    1987-01-01

    Decreased stature of children is epidemiologically associated with increased blood lead independent of multiple socioeconomic and nutritional variables. Since endocrine dysfunction occurs in adult lead workers, they studied two girls, 2 years of age, before and after calcium disodium edetate chelation for blood leads (PbB) of 19-72 μg/dl. The height of both children had crossed from the 50th to below the 10th percentile during the course of chronic lead toxicity. Basal free T 4 , T 4 , T 3 , cortisol, somatomedin C, and sex steroids were normal. A decrease in the growth hormone response and elevation of basal prolcatin and gonadotropins were noted in one. Both children demonstrated blunted thyrotropin-stimulating hormone (TSH) responses to thyrotropin-releasing hormone (TRH) in six of seven challenges. This prompted in vitro studies of cultured cells from rat pituitarities. After incubation of pituitary cells with 0.1-10 μM Pb 2+ for 2 hr, followed by the addition of TRH, there was a dose-dependent inhibition of TSH release Lead did not interfere with the assay of TSH. To investigate the interaction of lead and calcium, 45 Ca 2+ kinetic analyses were done on rat pituitary slices after 1 hr incubation with 1.0 μM lead. The impaired late efflux was consistent with a decrease in the size and exchangeability of the tightly bound pool of intracellular microsomal or mitochondrial calcium. The rat pituitary cell model provides a model for the decreased TSH release of lead poisoning, supports the biological plausibility of a neuroendocrine effect on growth, and suggests that interference with calcium-mediated intracellular responses is a basic mechanism of lead toxicity

  20. The effect of hormonal replacement therapy on breast

    International Nuclear Information System (INIS)

    Jeong, Mi Gyoung; Oh, Ki Keun; Kim, Mi Hye

    1995-01-01

    To evaluate mammographic and sonographic breast parenchymal changes and the risk of breast cancer in women on hormonal replacement therapy (HRT). The study group consisted of 50 patients examined with serial mammograms and/or ultrasonograms during HRT. The control group consisted of 50 patients examined with serial mammogram for a routine health check. Mammographic parenchymal changes in both the study and control groups and sonographic findings of 27/50 patients in study group were evaluated. Follow-up mammogram of the control group showed no interval change or slight evolution of parenchyma with increasing age, but the study group showed increasing parenchymal densities. Most frequently encountered finding on sonogram in 11 women treated by estrogen alone, was ductal dilatation (7 cases; 64%), whereas in 16 women treated by estrogen and progesteron it was ductal epithelial hyperplasia (8 cases; 50%). Overall, four breast cancers developed; one infiltrating ductal carcinoma and three ductal carcinoma in situ. HRT causes the changes of breast parenchyma on mammogram and sonogram of postmenopausal women, and increases the risk of developing breast cancer. Therefore, careful and regular examination should be followed in those on postmenopausal HRT

  1. Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes.

    Science.gov (United States)

    Espeland, Mark A; Brinton, Roberta Diaz; Manson, JoAnn E; Yaffe, Kristine; Hugenschmidt, Christina; Vaughan, Leslie; Craft, Suzanne; Edwards, Beatrice J; Casanova, Ramon; Masaki, Kamal; Resnick, Susan M

    2015-09-29

    To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p=0.002). This interaction was evident for total gray matter (pNeurology.

  2. Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

    Science.gov (United States)

    de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Willem Redeker, Egbert Johan; Eduard Santen, Gijs Willem; Henriëtta Verkerk, Annemieke Johanna Maria; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

    2017-12-15

    Cornelia de Lange syndrome (CdLS) is a both clinically and genetically heterogeneous syndrome. In its classical form, it is characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay, and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge, there are no reports on the effect of recombinant human GH treatment in CdLS patients. We present a patient born small for gestational age with persistent severe growth retardation [height -3.4 standard deviation score (SDS)] and mild dysmorphic features, who was treated with GH from 4.3 years of age onward and was diagnosed 6 years later with CdLS using whole-exome sequencing. Treatment led to a height gain of 1.6 SDS over 8 years. Treatment was interrupted shortly due to high serum insulin-like growth factor-1 serum values. In conclusion, GH therapy may be effective and safe for short children with CdLS.

  3. The ethics of aggregation and hormone replacement therapy.

    Science.gov (United States)

    Lyerly, A D; Myers, E R; Faden, R R

    2001-01-01

    The use of aggregated quality of life estimates in the formation of public policy and practice guidelines raises concerns about the moral relevance of variability in values in preferences for health care. This variability may reflect unique and deeply held beliefs that may be lost when averaged with the preferences of other individuals. Feminist moral theories which argue for attention to context and particularity underline the importance of ascertaining the extent to which differences in preferences for health states reveal information which is morally relevant to clinicians and policymakers. To facilitate these considerations, we present an empirical study of preferences for the timing and occurrence of health states associated with hormone replacement therapy (HRT). Sixteen women between the ages of 45 and 55 were enrolled in this pilot study. Their preferences regarding five health states associated with HRT (menopausal symptoms. side effects of HRT, breast cancer, myocardial infarction, and osteoporosis) were assessed in quantitative terms known as utilities. Two standard methods, the visual analog scale (VAS) and the standard gamble (SG), were used to assess utility and time preference (calculated as a discount rate). The wide variability of responses underlines the importance of tailoring health care to individual women's preferences. Policy guidelines which incorporate utility analysis must recognize the normative limitations of aggregated preferences, and the moral relevance of individual conceptions of health.

  4. Calcium-independent phosphatidylinositol response in gonadotropin-releasing-hormone-stimulated pituitary cells.

    OpenAIRE

    Naor, Z; Molcho, J; Zakut, H; Yavin, E

    1985-01-01

    This paper describes the effect of gonadotropin-releasing hormone (GnRH, gonadoliberin) on phospholipid metabolism in cultured rat pituitary cells. The cells were incubated with [32P]Pi to label endogenous phospholipids (10-60 min) and then stimulated with GnRH for up to 60 min. Cellular phospholipids were separated by two-dimensional t.l.c. and the radioactivity was determined. Phosphatidylinositol (PI), a minor constituent of cellular phospholipids (7.7%), was the major labelled phospholipi...

  5. Certain hormonal profiles of postpartum anestrus jersey crossbred cows treated with controlled internal drug release and ovsynch protocol

    Directory of Open Access Journals (Sweden)

    Dayanidhi Jena

    2016-10-01

    Full Text Available Aim: The study was conducted to determine the serum levels of certain hormones in post-partum anestrus cows following treatment with controlled internal drug release (CIDR and Ovsynch protocol. Materials and Methods: A total of 30 postpartum anestrus cows were divided into three equal groups after thorough gynecoclinical examination. The Group 1 animals received an intravaginal progesterone device on day 0 and 2 ml of prostaglandin F2α (PGF2α on day of CIDR removal (7th day, Group 2 cows were treated with ovsynch protocol (gonadotropinreleasing hormone [GnRH]-PGF2α-GnRH on day 0, 7 and 9, respectively, and Group 3 cows were supplemented with mineral mixture and treated as control. The serum estrogen, progesterone, triiodothyronine, and thyroxine concentration were estimated using enzyme-linked immunosorbent assay kit and absorbance was read at 450 nm with Perkin Elmer Wallac 1420 Microplate Reader. Results: There was a significant increase in progesterone level in Group 1 after withdrawal of CIDR as compared to other two groups. However, the estrogen assay revealed a greater concentration in Group 2 against Group 1 on day 7 of sampling. However, there was no significant difference for serum triiodothyronine (T3 and thyroxine (T4 irrespective of treatment protocols and days of sampling. Conclusion: Treatment with CIDR based progesterone therapy and drug combinations may affect the reproductive hormonal balance like estrogen and progesterone, which is inevitable for successful return to cyclicity and subsequent fertilization and conception. However, as far as serum T3 and T4 concentration concerned it may not give an astounding result.

  6. Response to growth hormone therapy in adolescents with familial panhypopituitarism.

    Science.gov (United States)

    Kulshreshtha, B; Eunice, M; Ammini, A C

    2010-04-01

    Familial combined pituitary hormone deficiency is a rare endocrine disorder. We describe growth patterns of four children (3 females and 1 male) from two families with combined pituitary hormone deficiency. These children received growth hormone at ages ranging from 14.5 years to 19 years. While all the female siblings reached their target height, the male sibling was much shorter than mid parental height. The reasons for sexual dimorphism in growth patterns in these children are unclear.

  7. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2018-04-01

    Full Text Available The neurohypophyseal hormone oxytocin (Oxt has been shown to stimulate prolactin (Prl synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr, namely isotocin (Ist receptor 1 (Istr1 and 2 (Istr2, were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  8. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Science.gov (United States)

    Yang, Wei; Zhang, Ning; Shi, Boyang; Zhang, Shen; Zhang, Lihong; Zhang, Weimin

    2018-01-01

    The neurohypophyseal hormone oxytocin (Oxt) has been shown to stimulate prolactin (Prl) synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr), namely isotocin (Ist) receptor 1 (Istr1) and 2 (Istr2), were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh) cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  9. Internalization and recycling of receptor-bound gonadotropin-releasing hormone agonist in pituitary gonadotropes

    International Nuclear Information System (INIS)

    Schvartz, I.; Hazum, E.

    1987-01-01

    The fate of cell surface gonadotropin-releasing hormone (GnRH) receptors on pituitary cells was studied utilizing lysosomotropic agents and monensin. Labeling of pituitary cells with a photoreactive GnRH derivative, [azidobenzoyl-D-Lys6]GnRH, revealed a specific band of Mr = 60,000. When photoaffinity-labeled cells were exposed to trypsin immediately after completion of the binding, the radioactivity incorporated into the Mr = 60,000 band decreased, with a concomitant appearance of a proteolytic fragment (Mr = 45,000). This fragment reflects cell surface receptors. Following GnRH binding, the hormone-receptor complexes underwent internalization, partial degradation, and recycling. The process of hormone-receptor complex degradation was substantially prevented by lysosomotropic agents, such as chloroquine and methylamine, or the proton ionophore, monensin. Chloroquine and monensin, however, did not affect receptor recycling, since the tryptic fragment of Mr = 45,000 was evident after treatment with these agents. This suggests that recycling of GnRH receptors in gonadotropes occurs whether or not the internal environment is acidic. Based on these findings, we propose a model describing the intracellular pathway of GnRH receptors

  10. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

    NARCIS (Netherlands)

    Martinelli, Ida; Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.

    2016-01-01

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation.

  11. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

    Science.gov (United States)

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-01-01

    Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  12. Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies.

    Science.gov (United States)

    Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C

    1979-05-01

    Inactivation of LHRH by purified bovine pituitary plasma membranes was studied in vitro. After incubation of [125I]iodo-LHRH with plasma membranes, the amount of tracer bound to the pellet was measured, and the integrity of the unbound tracer in the supernatant was assessed. Reduction in ability to bind to anti-LHRH serum and to rebind to plasma membranes together with altered electrophoretic mobility on polyacrylamide gels showed that the unbound [125I]iodo-LHRH was inactivated. LHRH inactivation occurred rapidly and was dependent upon membrane concentration and incubation temperature. These results indicate that hormone inactivation must be taken into account in the interpretation of LHRH-receptor interactions. During 37 C incubations, the apparent absence of specific LHRH binding can be explained by inactivation of tracer hormone. Significant LHRH inactivation also occurred at 0 C, which in part explains the insensitivity of LHRH receptor assays. Assessment of LHRH inactivation by different particulate subcellular fractions of pituitary tissue showed that the inactivating enzyme was associated with the plasma membranes; other organelles did not alter LHRH. The enzyme appeared to be an integral part of the plasma membrane structure, since enzymic activity could not be removed by washing without reducing specific LHRH binding. Additionally, reduction of LHRH inactivation by the inhibitors Bacitracin and Trasylol and by magnesium was also accompanied by reduced LHRH binding. Previous studies have shown that the majority of LHRH binding to pituitary plasma membranes is to the low affinity site (approximately 10(-6) M), but the significance of this binding has been uncertain. Our findings indicate that low affinity binding probably represents binding of LHRH to the inactivating enzyme. The LHRH analog, D-Ser6(TBu), des Gly10, ethylamide, has greater biological activity than LHRH and is not inactivated to a significant extent by pituitary plasma membranes. The

  13. Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats.

    Science.gov (United States)

    Maeng, L Y; Taha, M B; Cover, K K; Glynn, S S; Murillo, M; Lebron-Milad, K; Milad, M R

    2017-08-01

    Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Thyroid hormone therapy following the thyroidectomy for thyroid carcinoma

    International Nuclear Information System (INIS)

    Horster, F.A.

    1986-01-01

    Medication with thyroid hormones following total thyroidectomy for thyroid carcinoma is based on the following principles: 1. The patient is informed about the lifelong necessity of taking a thyroid hormones daily before breakfast. This hormone must be given orally and its bioligical effect is identical with that of the tyhroid hormone secreted by the healthy thyroid gland. 2. The daily dosage of thyroid hormones may be assessed on the basis of the following parameters: a) the patient's clinical euthyroidism, b) suppression of thyrotropic activity, c) unrestricted tolerance of the preparation. 3. The in vitro parameters associated with optimal medication should be within the following ranges: Thyroxine value (TT4 or FT4): above the normal range, triiodothyronine value (TT3 or FT3): within the upper normal range and thyrotropin value (TSH 'ultrasensitive' or TRH-test): suppressed. (orig.) [de

  15. Current attitudes on self-use and prescription of hormone therapy among New York City gynaecologists

    DEFF Research Database (Denmark)

    Devi, Gayatri; Sugiguchi, Fumitaka; Pedersen, Anette Tønnes

    2013-01-01

    The results of the Women's Health Initiative studies dramatically altered hormone therapy use around the world. In countries outside the United States, self-use in physicians remained unaltered while prescription use declined, implying that physicians may not concur with the findings. We wished t...... to explore prevailing attitudes among American physicians by examining New York City obstetrician-gynaecologists' self-use and prescription use of hormone therapy....

  16. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, H.E.; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  17. Double insemination and gonadotropin-releasing hormone treatment of repeat-breeding dairy cattle.

    Science.gov (United States)

    Stevenson, J S; Call, E P; Scoby, R K; Phatak, A P

    1990-07-01

    Our objective was to determine if double inseminations during the same estrous period of dairy cattle eligible for their third or fourth service (repeat breeders) would improve pregnancy rates equivalent to injections of GnRH given at the time of AI. Repeat-breeding, lactating cows from six herds (five herds in the San Joaquin Valley of central California and one herd in northeast Kansas) were assigned randomly to four treatment groups when detected in estrus: 1) single AI plus no injection, 2) single AI plus 100 micrograms GnRH at AI, 3) double AI plus no injection, or 4) double AI plus 100 micrograms of GnRH at AI. Inseminations were performed according to the a.m.-p.m. rule. The second AI for the double AI treatment was given 12 to 16 h after the first AI. Injections of GnRH were given intramuscularly immediately following the single AI or the first AI of the double AI. Pregnancy rates of cows given a single AI and hormone injection were numerically higher in all six herds than those of their herdmates given only a single AI. In five of six herds, the pregnancy rates of cows given a double AI and hormone injection were numerically higher than pregnancy rates of their herdmates given only a double AI. Overall pregnancy rates for the four treatments were 1) 112/353 (32.1%), 2) 165/406 (41.6%), 3) 119/364 (33.5%), and 4) 135/359 (37.5%). Gonadotropin-releasing hormone increased pregnancy rates of repeat breeders compared with controls given only a single AI. No further benefit beyond the single AI was accrued from the double AI treatment, with or without concurrent hormone administration.

  18. Impact of hormone therapy on quality of life after menopause.

    Science.gov (United States)

    Utian, Wulf H; Woods, Nancy Fugate

    2013-10-01

    Given the complexity of the literature on quality of life (QOL) and hormone therapy (HT) among women in the menopausal transition and postmenopause, the purposes of this integrative review were to (1) define QOL as a multidimensional construct; (2) review validated instruments for measurement of QOL; (3) review results of HT and QOL clinical trials that have used validated instruments; and (4) assess the effectiveness of HT on QOL, including health-related QOL (HRQOL), menopause-specific QOL (MSQOL), and global QOL (GQOL). The literature on HT and QOL was searched for definitions of QOL and validated instruments for measuring QOL, and the results were summarized. The purposes of this integrative review were to evaluate the effects of HT on HRQOL, differentiating the effects of HT on GQOL, HRQOL, and MSQOL. As a basis for this review, we searched for published controlled clinical trials in which the effects of HT on QOL were studied using validated QOL instruments, in particular menopause-specific validated instruments. Clear definitions are elucidated. Validated instruments for the measurements of HRQOL, GQOL, and MSQOL are summarized, and the necessity of their incorporation into future research and clinical practice is emphasized. The published effects on QOL of estrogens and progestogens administered to symptomatic and nonsymptomatic women in the menopausal transition and beyond are reviewed. The impact of various health state-related symptoms on HRQOL and GQOL is now an integral component of contemporary health care. Effects of HT include GQOL and HRQOL and should be menopause-specific. There is clearly a need for further studies on menopause and menopause-related therapies using appropriate and validated instruments. Literature review shows that HT provides a significant benefit for MSQOL in midlife women, mainly through relief of symptoms, but treatment also may result in a global increase in sense of well-being (GQOL). HRQOL benefits are contingent on

  19. Endocrinology and hormone therapy in breast cancer: Endocrine therapy in premenopausal women

    International Nuclear Information System (INIS)

    Pritchard, Kathleen

    2005-01-01

    Endocrine therapy remains important in premenopausal women with hormone receptor positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that it is effective perhaps because of the endocrine ablative effect of chemotherapy. Trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors have estrogen and/or progesterone receptor. Tamoxifen is also effective in preventing recurrence and prolonging survival in the adjuvant setting in premenopausal women. While most of the available data deals with tamoxifen given alone, it appears to have a similar beneficial effect when added to chemotherapy in the premenopausal adjuvant setting. Adjuvant aromatase inhibitors should not be used in premenopausal women

  20. [Puberty-delaying hormone therapy in adolescents with gender identity disorder].

    Science.gov (United States)

    Nakatsuka, Mikiya

    2013-01-01

    The guideline for the treatment of people with gender identity disorder (GID) of the Japanese Society of Psychiatry and Neurology was revised in January 2012. The guideline eased restrictions for the endocrine treatment of transsexual adolescents. A medical specialist can start treating transsexual adolescents at the age of 15 after the diagnosis of GID. It recommends that transsexual adolescents (Tanner stage 2 [mainly 12-13 years of age]) are treated by endocrinologists to suppress puberty with gonadotropin-releasing hormone (GnRH) agonists until the age of 15 years old, after which cross-sex hormones may be given. Female-to-male transsexuals do not necessarily want to start androgen therapy before presenting female secondary sexual characteristics because androgen can easily stop menstruation, cause beard growth, and lower the voice. On the contrary, male-to-female transsexuals want to start estrogen therapy before presenting male secondary sexual characteristics because estrogen cannot alter the beard and low voice. It is important to identify children with gender dysphoria in school and help them receive medical advice. However, approximately half of school teachers think that children with gender dysphoria are very rare and they do not know of the notification from Ministry of Education, Culture, Sports, Science and Technology, JAPAN, which aims to help children with gender dysphoria. The revision of the guideline for the treatment of transsexual people and endocrine treatment of transsexual adolescents by medical specialists may prevent them from attempting suicide, being depressive, and refusing to attend school. Furthermore, the treatment may help avoid mental disorders, aid being employed with the desired sexuality, and, subsequently, getting married and having children.

  1. How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis.

    Science.gov (United States)

    Brunson, K L; Eghbal-Ahmadi, M; Baram, T Z

    2001-11-01

    West syndrome (WS) is associated with diverse etiological factors. This fact has suggested that there must be a 'final common pathway' for these etiologies, which operates on the immature brain to result in WS only at the maturational state present during infancy. Any theory for the pathogenesis of WS has to account for the unique features of this disorder. For example, how can a single entity have so many etiologies? Why does WS arise only in infancy, even when a known insult had occurred prenatally, and why does it disappear? Why is WS associated with lasting cognitive dysfunction? And, importantly, why do these seizures--unlike most others--respond to treatment by a hormone, ACTH? The established hormonal role of ACTH in human physiology is to function in the neuroendocrine cascade of the responses to all stressful stimuli, including insults to the brain. As part of this function, ACTH is known to suppress the production of corticotropin releasing hormone (CRH), a peptide that is produced in response to diverse insults and stressors.The many etiologies of WS all lead to activation of the stress response, including increased production and secretion of the stress-neurohormone CRH. CRH has been shown, in infant animal models, to cause severe seizures and death of neurons in areas involved with learning and memory. These effects of CRH are restricted to the infancy period because the receptors for CRH, which mediate its action on neurons, are most abundant during this developmental period. ACTH administration is known to inhibit production and release of CRH via a negative feedback mechanism. Therefore, the efficacy of ACTH for WS may depend on its ability to decrease the levels of the seizure-promoting stress-neurohormone CRH.This CRH-excess theory for the pathophysiology of WS is consistent not only with the profile of ACTH effects, but also with the many different 'causes' of WS, with the abnormal ACTH levels in the cerebrospinal fluid of affected infants and

  2. Gonadotropin-Releasing Hormone Regulates Expression of the DNA Damage Repair Gene, Fanconi anemia A, in Pituitary Gonadotroph Cells1

    OpenAIRE

    Larder, Rachel; Chang, Lynda; Clinton, Michael; Brown, Pamela

    2004-01-01

    Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse LβT2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regu...

  3. Evidence-based practice in women's health: hormone therapy for women at menopause.

    Science.gov (United States)

    Rousseau, M E

    2001-01-01

    Women's health providers, especially midwives, must take into account the known benefits and risks, as well as the "unknown," when recommending the use of hormone therapy for menopausal women, especially as it relates to heart disease, breast cancer, impaired cognition, and osteoporosis. The most recent evidence available from various studies about the benefits and risks of estrogen and hormone therapy at menopause suggests that, although hormone therapy may be protective in some women against heart disease and osteoporosis, evidence is less certain about the benefits of hormone protection against impaired cognition and the risks of breast cancer with use. The clinical approach used by midwives in which individualizing care based on each woman's health status history as well as preferences is highly appropriate for women in the perimenopausal and menopausal period.

  4. Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats.

    Directory of Open Access Journals (Sweden)

    Ippolita Cantuti-Castelvetri

    2010-11-01

    Full Text Available Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition.Quantitative real-time polymerase chain reaction (PCR was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes.TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.

  5. Towards more physiological manipulations of hormones in field studies: comparing the release dynamics of three kinds of testosterone implants, silastic tubing, time-release pellets and beeswax.

    Science.gov (United States)

    Quispe, Rene; Trappschuh, Monika; Gahr, Manfred; Goymann, Wolfgang

    2015-02-01

    Hormone manipulations are of increasing interest in the areas of physiological ecology and evolution, because hormones are mediators of complex phenotypic changes. Often, however, hormone manipulations in field settings follow the approaches that have been used in classical endocrinology, potentially using supra-physiological doses. To answer ecological and evolutionary questions, it may be important to manipulate hormones within their physiological range. We compare the release dynamics of three kinds of implants, silastic tubing, time-release pellets, and beeswax pellets, each containing 3mg of testosterone. These implants were placed into female Japanese quail, and plasma levels of testosterone measured over a period of 30 days. Testosterone in silastic tubing led to supraphysiological levels. Also, testosterone concentrations were highly variable between individuals. Time-release pellets led to levels of testosterone that were slightly supraphysiological during the first days. Over the period of 30 days, however, testosterone concentrations were more consistent. Beeswax implants led to a physiological increase in testosterone and a relatively constant release. The study demonstrated that hormone implants in 10mm silastic tubing led to a supraphysiological peak in female quail. Thus, the use of similar-sized or even larger silastic implants in males or in other smaller vertebrates needs careful assessment. Time-release pellets and beeswax implants provide a more controlled release and degrade within the body. Thus, it is not necessary to recapture the animal to remove the implant. We propose beeswax implants as an appropriate procedure to manipulate testosterone levels within the physiological range. Hence, such implants may be an effective alternative for field studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Jayasena, C N; Nijher, G M K; Abbara, A; Murphy, K G; Lim, A; Patel, D; Mehta, A; Todd, C; Donaldson, M; Trew, G H; Ghatei, M A; Bloom, S R; Dhillo, W S

    2010-12-01

    Kisspeptin is a novel therapeutic target for infertility. A single kisspeptin-54 (KP-54) injection acutely stimulates the release of reproductive hormones in women with hypothalamic amenorrhea (HA), a commonly occurring condition characterized by absence of menstruation; however, twice-daily administration of KP-54 results in tachyphylaxis. We determined the time course of desensitization to twice-daily KP-54 injections, compared the effects of twice-daily and twice-weekly administration regimens of KP-54, and studied the effects of long-term twice-weekly administration of KP-54 on the release of reproductive hormones in women with HA. When KP-54 was administered twice daily, responsiveness to luteinizing hormone (LH) diminished gradually, whereas responsiveness to follicle-stimulating hormone (FSH) was nearly abolished by day 2. Twice-weekly KP-54 administration resulted in only partial desensitization, in contrast to the complete tolerance achieved with twice-daily administration. Women with HA who were treated with twice-weekly KP-54 injections had significantly elevated levels of reproductive hormones after 8 weeks as compared with treatment with saline. No adverse effects were observed. This study provides novel pharmacological data on the effects of KP-54 on the release of reproductive hormones in women with HA.

  7. Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer. Comparison of two different definitions of PSA failure

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Sasaki, Yoshihide; Mizowaki, Takashi

    2006-01-01

    We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the ''nadir plus 2'' definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial. (author)

  8. The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Whittington, Richard; Malkowicz, S Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M; Broderick, Gregory A; Wein, Alan J

    1997-10-01

    Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

  9. The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer

    International Nuclear Information System (INIS)

    Whittington, Richard; Malkowicz, S. Bruce; Machtay, Mitchell; Van Arsdalen, Keith; Barnes, Margaret M.; Broderick, Gregory A.; Wein, Alan J.

    1997-01-01

    Purpose: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. Methods and Materials: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). Results: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. Conclusion: Combined hormonal and radiation therapy represents an effective treatment option for patients with

  10. Hormone replacement therapy in postmenopause - where we stand?

    Directory of Open Access Journals (Sweden)

    Damir Franić

    2007-02-01

    Full Text Available Background: The findings of most relevant randomized clinical studies such as HERS, WHI and MWS, performed in the last decade have shown that hormonal replacement therapy (HRT users are at increased risk for the development of breast cancer, stroke and pulmonary edema. On the other hand they are at a lower risk for the development of large bowel cancer and for hip and vertebral fractures; the incidences of endometrial cancer and coronary heart disease have not been proved to be significantly affected by HRT. As for the prevention of cardiovascular diseases, the findings of these studies differed from those provided by observational studies, it became an imperative to find the causes of these discrepancies. The major criticism of randomized clinical studies was aimed at the inclusion criteria, as the mean women’s age in HERS and in WHI study was 63 years. The women of that age may no longer be healthy, and are particularly exposed to cardiovascular diseases. In all studies the same type of HRT was used, i.e. conjugated equine estrogen alone or in combination with medroxyprogesterone acetate. In Europe, this combination is rarely prescribed; we do not prescribe it in Slovenia either. The same type of HRT used in randomized clinical studies was further criticized, the basic idea of HRT being an individual approach to each woman requiring HRT. For rather sensational and often misinterpreted findings of randomized studies, the largest menopause societies worldwide, the International Menopause Society (IMS, the European Menopause and Andropause Society (EMAS and the North American Menopause Society (NAMS, have revised the guidelines for HRT use in postmenopause. These guidelines have been adopted by the Slovene Menopause Society as well.Conclusions: The indications for HRT remain to be markedly expressed and severe climacteric symptoms, prevention and treatment of osteoporosis, urogenital syndrome and premature menopause. However, the

  11. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N

    2005-01-01

    Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL) secretion in various vertebrates including the tilapia, Oreochromis mossambicus. The mechanism by which GnRH regulates lactotroph cell function is poorly understood. Using the advantageous characteristics of the teleost...

  12. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

    Directory of Open Access Journals (Sweden)

    Stefan Lim

    Full Text Available The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta and follicle-stimulating hormone beta-subunit (FSHbeta. Three mitogen-activated protein kinases, (MAPKs, ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R. Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

  13. Menopause and menopausal hormone therapy in women: cardiovascular benefits and risks

    Directory of Open Access Journals (Sweden)

    Anna Svatikova

    2018-01-01

    Full Text Available The last decade has brought many challenges and uncertainties regarding the use of menopausal hormone therapy in women. Two early key studies, the Heart and Estrogen/Progestin Replacement Study (HERS and the Women's Health Initiative (WHI failed to prove beneficial effects of exogenous estrogen, and estrogen combined with progestin, in cardiovascular prevention. More recent studies, however, introduced the concept of a possible “window-of-opportunity” for hormonal therapy, in which menopausal hormone therapy is used early after the onset of menopause, and may lead to more favorable, cardio-protective outcomes. Despite the increasing wealth of clinical data, menopausal hormone therapy is not currently recommended for primary or secondary prevention of coronary heart disease in women. Further research is needed to understand the risk-benefit balance of menopausal hormone therapy. Resumen: La última década ha traído muchos retos e incertidumbres respecto al uso de la terapia hormonal en la menopausia en mujeres. Dos estudios tempranos clave, el Heart and Estrogen/Progestin Replacement Study (HERS [Estudio del Corazón y Reemplazo de Estrógeno/Progestina] y la Womeńs Health Initiative (WHI [Iniciativa de Salud de la Mujer] no pudieron demostrar los efectos benéficos del estrógeno exógeno y el estrógeno combinado con la progestina, en la prevención cardiovascular. Sin embargo, estudios más recientes han introducido el concepto de una posible “ventana de oportunidad” para la terapia hormonal, en donde la terapia hormonal en la menopausia se emplea tempranamente luego del inicio de la menopausia, y que puede llevar a resultados más favorables y cardioprotectores. A pesar de la creciente riqueza en datos clínicos, en la actualidad no se recomienda la terapia hormonal en la menopausia para la prevención primaria o secundaria de la enfermedad coronaria en mujeres. Se requiere m

  14. Effect of thyrotrophin releasing hormone on opiate receptors of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Balashov, A.M.; Shchurin, M.R.

    1987-01-01

    It has recently been shown that the hypothalamic thyrotropin releasing hormone (TRH) has the properties of a morphine antagonist, blocking its inhibitory action on respiration and, to a lesser degree, its analgesic action. This suggests that the antagonistic effects of TRH are mediated through its interaction with opiate receptors. The aim of this paper is to study this hypothesis experimentally. Tritium-labelled enkephalins in conjunction with scintillation spectroscopy were used to assess the receptor binding behavior. The results indicate the existence of interconnections between the opiate systems and TRH. Although it is too early to reach definite conclusions on the mechanisms of this mutual influence and its physiological significance it can be tentatively suggested that TRH abolishes the pharmacological effects of morphine by modulating the functional state of opiate reception.

  15. Pituitary Apoplexy After Thyrotropin-releasing Hormone Stimulation Test in a Patient with Pituitary Macroadenoma

    Directory of Open Access Journals (Sweden)

    Huei-Fang Wang

    2007-09-01

    Full Text Available Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH 200 mg intravenous injection stimulation test. Neither emergency computed tomography (CT scans nor magnetic resonance imaging (MRI, performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

  16. Regulation of feeding behavior and psychomotor activity by corticotropin-releasing hormone (CRH in fish

    Directory of Open Access Journals (Sweden)

    Kouhei eMatsuda

    2013-05-01

    Full Text Available Corticotropin-releasing hormone (CRH is a hypothalamic neuropeptide belonging to a family of neuropeptides that includes urocortins, urotensin I and sauvagine in vertebrates. CRH and urocortin act as anorexigenic factors for satiety regulation in fish. In a goldfish model, intracerebroventricular (ICV administration of CRH has been shown to affect not only food intake, but also locomotor and psychomotor activities. In particular, CRH elicits anxiety-like behavior as an anxiogenic neuropeptide in goldfish, as is the case in rodents. This paper reviews current knowledge of CRH and its related peptides derived from studies of teleost fish, as representative non-mammals, focusing particularly on the role of the CRH system, and examines its significance from a comparative viewpoint.

  17. Mammographic changes in postmenopausal women : comparative effects between continuous combined hormone and single estrogen replacement therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sug; Choi, Jong Tae; Jung, Kyoon Soon; Jung, Seung Hye [Jeil Women' s Hospital, Seoul (Korea, Republic of)

    1997-06-01

    As the use of hormone replacement therapy for the menopausal women increases, some caution is advised, since there is an increased risk of breast cancer. Accordingly, the importance of regular mammography has been addressed. This cross-setional study analyzed the effects of different hormone therapies on mammographic density. Sixty-seven postemenopausal women who had completed one year of hormone therapy and had undergone follow-up mammography, were divided into two groups : Group I : continuous conjugated equine estrogen, 0.625mg, plus continuous medroxyprogesterone acetate, 2.5mg (n=48), Group II : continuous conjugated equine estrogen 0.625mg (n=19). The mammograms were read by two radiologists. With regard to the radiologists involved, interobserver reliabillity (kappa) was 0.70 and intraobserver reliability (kappa) was 0.51 and 0.67. Before hormone therapy, factors related to decreased mammographic density were age and number of full term pregnancies (p<0.05). After one year of hormone therapy, body fat showed a significant increase (p<0.05), but in spite of this, increased mammographic density induced by hormone therapy remained significantly high (p<0.05). Compared with Group II, Group I showed a significant increase in mammographic density (p<0.05). In Group I, mammographic density increased from P2 to DY pattern in two cases, but there was no such change in Group II. The increase of mammographic density seen in Group II was much more significant statistically than that seen in Group I. The mammograms of women who have undergone continuous combined hormone therapy should therefore be interpreted very cautiously.

  18. Mammographic changes in postmenopausal women : comparative effects between continuous combined hormone and single estrogen replacement therapy

    International Nuclear Information System (INIS)

    Oh, Sug; Choi, Jong Tae; Jung, Kyoon Soon; Jung, Seung Hye

    1997-01-01

    As the use of hormone replacement therapy for the menopausal women increases, some caution is advised, since there is an increased risk of breast cancer. Accordingly, the importance of regular mammography has been addressed. This cross-setional study analyzed the effects of different hormone therapies on mammographic density. Sixty-seven postemenopausal women who had completed one year of hormone therapy and had undergone follow-up mammography, were divided into two groups : Group I : continuous conjugated equine estrogen, 0.625mg, plus continuous medroxyprogesterone acetate, 2.5mg (n=48), Group II : continuous conjugated equine estrogen 0.625mg (n=19). The mammograms were read by two radiologists. With regard to the radiologists involved, interobserver reliabillity (kappa) was 0.70 and intraobserver reliability (kappa) was 0.51 and 0.67. Before hormone therapy, factors related to decreased mammographic density were age and number of full term pregnancies (p<0.05). After one year of hormone therapy, body fat showed a significant increase (p<0.05), but in spite of this, increased mammographic density induced by hormone therapy remained significantly high (p<0.05). Compared with Group II, Group I showed a significant increase in mammographic density (p<0.05). In Group I, mammographic density increased from P2 to DY pattern in two cases, but there was no such change in Group II. The increase of mammographic density seen in Group II was much more significant statistically than that seen in Group I. The mammograms of women who have undergone continuous combined hormone therapy should therefore be interpreted very cautiously

  19. Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer

    International Nuclear Information System (INIS)

    Barni, S.; Lissoni, P.; Tancini, G.

    1986-01-01

    While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demostrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation

  20. Nonreproductive role of gonadotropin-releasing hormone in the control of ascidian metamorphosis.

    Science.gov (United States)

    Kamiya, Chisato; Ohta, Naoyuki; Ogura, Yosuke; Yoshida, Keita; Horie, Takeo; Kusakabe, Takehiro G; Satake, Honoo; Sasakura, Yasunori

    2014-12-01

    Gonadotropin-releasing hormones (GnRHs) are neuropeptides that play central roles in the reproduction of vertebrates. In the ascidian Ciona intestinalis, GnRHs and their receptors are expressed in the nervous systems at the larval stage, when animals are not yet capable of reproduction, suggesting that the hormones have non-reproductive roles. We showed that GnRHs in Ciona are involved in the animal's metamorphosis by regulating tail absorption and adult organ growth. Absorption of the larval tail and growth of the adult organs are two major events in the metamorphosis of ascidians. When larvae were treated with GnRHs, they completed tail absorption more frequently than control larvae. cAMP was suggested to be a second messenger for the induction of tail absorption by GnRHs. tGnRH-3 and tGnRH-5 (the "t" indicates "tunicate") inhibited the growth of adult organs by arresting cell cycle progression in parallel with the promotion of tail absorption. This study provides new insights into the molecular mechanisms of ascidian metamorphosis conducted by non-reproductive GnRHs. © 2014 Wiley Periodicals, Inc.

  1. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

    Science.gov (United States)

    Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H

    2016-03-17

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. © 2016 by The American Society of Hematology.

  2. Hormone therapy alters the composition of the vaginal microflora in ovariectomized rats.

    Science.gov (United States)

    Bezirtzoglou, E; Voidarou, Ch; Papadaki, A; Tsiotsias, A; Kotsovolou, O; Konstandi, M

    2008-05-01

    The aim of the present study was to evaluate the alterations that may take place in the bacterial genital tract flora in the absence of ovarian hormones. The role of hormone replacement therapy was also assessed. For this purpose, various bacteria were identified from the vaginal flora of ovariectomized and sham operated female rats, following the Bergey's manual criteria. The data of this study showed that substantial differences exist in the vaginal bacterial microflora between ovariectomized and normal cyclic rats. Ovariectomy was associated with a lower total bacterial load that may be due mainly to the absence of Lactobacillus. Anaerobic bacteria were also absent. Streptococcus and Enterococcus were also not favored in an environment lacking the ovarian hormones. In contrast, C. perfringens, Bacteroides, S. epidermidis, and S. aureus were detected in high numbers in ovariectomized rats. In terms of the impact of hormone replacement therapy on vaginal flora, only estradiol (EE2) restored Lactobacillus levels in ovariectomized rats, whereas all hormonal schemes used brought Streptococcus, Clostridium lec (-), and C. perfringens, the spore and vegetative forms, close to those detected in normal cyclic female rats. In conclusion, ovarian hormones appeared to be regulatory factors that favor the presence of a broad variety of bacteria, which are members of the normal genital tract flora. On the other hand, ovariectomy modifies the vaginal microbial profile, and hormone replacement therapy based mainly on schemes containing EE2 could alleviate this disturbance.

  3. Outcome after discontinuing anticoagulant therapy in women with venous thromboembolism during hormonal use.

    Science.gov (United States)

    Blanco-Molina, Ángeles; Trujillo-Santos, Javier; Pesavento, Raffaele; Rosa, Vladimir; Falgá, Conxita; Tolosa, Carles; Mazzolai, Lucia; Sampériz, Ángel; Duce, Rita; Monreal, Manuel

    2017-03-01

    Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having "unprovoked" or "provoked" VTE is controversial. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53-3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97-8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50-4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18-1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09-1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07-4.10). After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors. © 2017 Elsevier Ltd. All rights reserved.

  4. Alterations in the corticotropin-releasing hormone (CRH) neurocircuitry: Insights into post stroke functional impairments.

    Science.gov (United States)

    Barra de la Tremblaye, P; Plamondon, H

    2016-07-01

    Although it is well accepted that changes in the regulation of the hypothalamic-pituitary adrenal (HPA) axis may increase susceptibility to affective disorders in the general population, this link has been less examined in stroke patients. Yet, the bidirectional association between depression and cardiovascular disease is strong, and stress increases vulnerability to stroke. Corticotropin-releasing hormone (CRH) is the central stress hormone of the HPA axis pathway and acts by binding to CRH receptors (CRHR) 1 and 2, which are located in several stress-related brain regions. Evidence from clinical and animal studies suggests a role for CRH in the neurobiological basis of depression and ischemic brain injury. Given its importance in the regulation of the neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation to stress, CRH is likely associated in the pathophysiology of post stroke emotional impairments. The goals of this review article are to examine the clinical and experimental data describing (1) that CRH regulates the molecular signaling brain circuit underlying anxiety- and depression-like behaviors, (2) the influence of CRH and other stress markers in the pathophysiology of post stroke emotional and cognitive impairments, and (3) context and site specific interactions of CRH and BDNF as a basis for the development of novel therapeutic targets. This review addresses how the production and release of the neuropeptide CRH within the various regions of the mesocorticolimbic system influences emotional and cognitive behaviors with a look into its role in psychiatric disorders post stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Gonadotropin-releasing hormone agonist triggering of oocyte maturation in assisted reproductive technology cycles

    Directory of Open Access Journals (Sweden)

    Engin Türkgeldi

    2015-06-01

    Full Text Available Gonadotropin-releasing hormone agonists (GnRHa have gained increasing attention in the last decade as an alternative trigger for oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS. They provide a short luteinizing hormone (LH peak that limits the production of vascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showed similar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG triggering; however, lower pregnancy rates and higher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in fresh transfers. Intensive luteal phase support (iLPS involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS has been shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, such as in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, this method results in statistically similar ongoing pregnancy rates (although slightly lower than to those of hCG triggered cycles. GnRHa triggering decreased OHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservation and did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH surge, similar to natural cycles. Its possible benefits have been investigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urge further exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHa triggering

  6. The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene.

    Science.gov (United States)

    Baumann, G; Maheshwari, H

    1997-11-01

    We report the discovery of a cluster of severe familial dwarfism in two villages in the Province of Sindh in Pakistan. Dwarfism is proportionate and occurs in members of a kindred with a high degree of consanguinity. Only the last generation is affected, with the oldest dwarf being 28 years old. The mode of inheritance is autosomal recessive. Phenotype analysis and endocrine testing revealed isolated growth hormone deficiency (GHD) as the reason for growth failure. Linkage analysis for the loci of several candidate genes yielded a high lod score for the growth hormone-releasing hormone receptor (GHRH-R) locus on chromosome 7. Amplification and sequencing of the GHRH-R gene in affected subjects demonstrated an amber nonsense mutation (GAG-->TAG; Glu50-->Stop) in exon 3. The mutation, in its homozygous form, segregated 100% with the dwarf phenotype. It predicts a truncation of the GHRH-R in its extracellular domain, which is likely to result in a severely disabled or non-existent receptor protein. Subjects who are heterozygous for the mutation show mild biochemical abnormalities in the growth hormone-releasing hormone (GHRH)--growth hormone--insulin-like growth factor axis, but have only minimal or no growth retardation. The occurrence of an offspring of two dwarfed parents indicates that the GHRH-R is not necessary for fertility in either sex. We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH-R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD.

  7. Hormonal induction of gamete release, and in-vitro fertilisation, in the critically endangered Southern Corroboree Frog, Pseudophryne corroboree

    Directory of Open Access Journals (Sweden)

    Silla Aimee J

    2010-11-01

    Full Text Available Abstract Background Conservation Breeding Programs (CBP's are playing an important role in the protection of critically endangered anuran amphibians, but for many species recruitment is not successful enough to maintain captive populations, or provide individuals for release. In response, there has been an increasing focus on the use of Assisted Reproductive Technologies (ART, including the administration of reproductive hormones to induce gamete release followed by in vitro fertilisation. The objective of this study was to test the efficacy of two exogenous hormones to induce gamete release, for the purpose of conducting in vitro fertilisation (IVF, in one of Australia's most critically endangered frog species, Pseudophryne corroboree. Methods Male frogs were administered a single dose of either human chorionic gonadotropin (hCG or luteinizing hormone-releasing hormone (LHRHa, while female frogs received both a priming and ovulatory dose of LHRHa. Spermiation responses were evaluated at 3, 7, 12, 24, 36, 48, 60 and 72 h post hormone administration (PA, and sperm number and viability were quantified using fluorescent microscopy. Ovulation responses were evaluated by stripping females every 12 h PA for 5 days. Once gametes were obtained, IVF was attempted by combining spermic urine with oocytes in a dilute solution of simplified amphibian ringer (SAR. Results Administration of both hCG and LHRHa induced approximately 80% of males to release sperm over 72 h. Peak sperm release occurred at 12 h PA for hCG treated males and 36 h PA for LHRHa treated males. On average, LHRHa treated males released a significantly higher total number of live sperm, and a higher concentration of sperm, over a longer period. In female frogs, administration of LHRHa induced approximately 30% of individuals to release eggs. On average, eggs were released between 24 and 48 h PA, with a peak in egg release at 36 h PA. IVF resulted in a moderate percentage (54.72% of eggs

  8. Menopausal hormone therapy is associated with having high blood pressure in postmenopausal women: observational cohort study.

    Science.gov (United States)

    Chiu, Christine L; Lujic, Sanja; Thornton, Charlene; O'Loughlin, Aiden; Makris, Angela; Hennessy, Annemarie; Lind, Joanne M

    2012-01-01

    The relationship between menopausal hormone therapy (MHT) and cardiovascular risk remains controversial, with a number of studies advocating the use of MHT in reducing risk of cardiovascular diseases, while others have shown it to increase risk. The aim of this study was to determine the association between menopausal hormone therapy and high blood pressure. A total of 43,405 postmenopausal women were included in the study. Baseline data for these women were sourced from the 45 and Up Study, Australia, a large scale study of healthy ageing. These women reported being postmenopausal, having an intact uterus, and had not been diagnosed with high blood pressure prior to menopause. Odds ratios for the association between MHT use and having high blood pressure were estimated using logistic regression, stratified by age (high blood pressure: past menopausal hormone therapy use: high blood pressure, with the effect of hormone therapy use diminishing with increasing age. Menopausal hormone therapy use is associated with significantly higher odds of having high blood pressure, and the odds increase with increased duration of use. High blood pressure should be conveyed as a health risk for people considering MHT use.

  9. Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

    Science.gov (United States)

    De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

    2016-01-01

    Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

  10. Gonadotropin-releasing hormone radioimmunoassay and its measurement in normal human plasma, secondary amenorrhea, and postmenopausal syndrome

    International Nuclear Information System (INIS)

    Rosenblum, N.G.; Schlaff, S.

    1976-01-01

    A sensitive and specific double antibody radioimmunoassay for gonadotropin-releasing hormone (GnRH) has been developed for measurement in ethanol extracts of human plasma. Iodinated hormone was prepared with the use of the chloramine-T method, and antibodies were developed in rabbits over a six-month period with a GnRH synthetic copolymer immunogen. A Scatchard plot revealed at least three species of antibody. The assay can measure conservatively at the 5 pg. per milliliter level and shows no cross-reactivity with other available hypothalamic and pituitary hormones. The releasing hormone was quantitatively recovered from human plasma with immunologic identity to native hormone. Unextracted plasma could not be used because of nonspecific displacement. The measurement of GnRH in individuals receiving 100 μg of intravenous bolus infusions of the synthetic decapeptide show extremely elevated values with two half-lives: one of two to four minutes and another of 35 to 40 minutes. In our experiments, we have found measurable GnRH in patients with secondary amenorrhea and at the midcycle in normal women. In the normal cycling woman during the follicular and luteal phases, GnRH was undetectable. In postmenopausal women with extreme hypoestrogenism and markedly elevated luteinizing hormone values, GnRH was also undetectable. No bursts of GnRH could be detected in normal men when sampled every ten minutes over a two-hour period and every two hours throughout the day

  11. Dietary therapy of obesity: Effect on some hormonal and ...

    African Journals Online (AJOL)

    It is now clear that the presence of obesity substantially increases the risk of related co-morbidities such as insulin resistance, diabetes, dyslipidemia, hypertension and others. The objective of this study was to measure adiponectin, insulin hormones, and homocysteine concentrations in obese Egyptian women before and ...

  12. Hormone replacement therapy in Denmark, 1995-2004

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Lidegaard, Ojvind; Møller, Lisbeth Nørgaard

    2007-01-01

    Recently, the Danish National Register of Medicinal Product Statistics (NRM) was opened for research purposes, and therefore, on an individual basis, can merge with other national registers. The aim of this study was to analyse the use of hormones based on the individual data of the entire Danish...

  13. Gonadotropin-releasing hormone antagonist use in controlled ovarian stimulation and intrauterine insemination cycles in women with polycystic ovary syndrome.

    Science.gov (United States)

    Ertunc, Devrim; Tok, Ekrem C; Savas, Aysun; Ozturk, Ilay; Dilek, Saffet

    2010-03-01

    To observe the effects of ganirelix on controlled ovarian stimulation and intrauterine insemination (COS/IUI) cycles in women with polycystic ovary syndrome (PCOS). Prospective, randomized, controlled clinical study. An academic clinical research center. Women with PCOS and anovulatory infertility undergoing COS/IUI. Recombinant FSH therapy was started on day 3. In women assigned to the control group (n = 47), treatment was continued up to the day of hCG administration. In patients assigned to receive GnRH antagonist (n = 42), ganirelix was added when the leading follicle was > or =14 mm. Pregnancy rates, serum E(2), P, and LH levels, and follicle numbers at hCG day, prevalence of premature luteinization, and cost of stimulation. Serum E(2), P, and LH levels were significantly lower in the ganirelix group. Although premature luteinization and cycle cancellation was encountered less in the ganirelix group, the pregnancy rates per cycle were similar (15.4% vs. 10.7%). Patients would pay 6,153 dollars more for each pregnancy when using ganirelix. Gonadotropin-releasing hormone antagonist resulted in more monofollicular development, less premature luteinization, and less cycle cancellation in IUI cycles of patients with PCOS; however, the cost of stimulation increased without an improvement in pregnancy rates. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Toward developing recombinant gonadotropin-based hormone therapies for increasing fertility in the flatfish Senegalese sole.

    Directory of Open Access Journals (Sweden)

    François Chauvigné

    Full Text Available Captive flatfishes, such as the Senegalese sole, typically produce very low volumes of sperm. This situation is particularly prevalent in the first generation (F1 of reared sole males, which limits the development of artificial fertilization methods and the implementation of selective breeding programs. In this study, we investigated whether combined treatments with homologous recombinant follicle-stimulating (rFsh and luteinizing (rLh hormones, produced in a mammalian host system, could stimulate spermatogenesis and enhance sperm production in Senegalese sole F1 males. In an initial autumn/winter experiment, weekly intramuscular injections with increasing doses of rFsh over 9 weeks resulted in the stimulation of gonad weight, androgen release, germ cell proliferation and entry into meiosis, and the expression of different spermatogenesis-related genes, whereas a subsequent single rLh injection potentiated spermatozoa differentiation. In a second late winter/spring trial corresponding to the sole's natural prespawning and spawning periods, we tested the effect of repeated rLh injections on the amount and quality of sperm produced by males previously treated with rFsh for 4, 6, 8 or 10 weeks. These latter results showed that the combination of rFsh and rLh treatments could increase sperm production up to 7 times, and slightly improve the motility of the spermatozoa, although a high variability in the response was found. However, sustained administration of rFsh during spawning markedly diminished Leydig cell survival and the steroidogenic potential of the testis. These data suggest that in vivo application of rFsh and rLh is effective at stimulating spermatogenesis and sperm production in Senegalese sole F1 males, setting the basis for the future establishment of recombinant gonadotropin-based hormone therapies to ameliorate reproductive dysfunctions of this species.

  15. Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review.

    Science.gov (United States)

    Deodati, Annalisa; Cianfarani, Stefano

    2011-03-11

    To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. Systematic review. Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomised controlled trials from 1985 to April 2010. Height in adulthood (standard deviation score) and overall gain in height (SD score) from baseline measurement in childhood. Randomised and non-randomised controlled trials with height measurements for adults. Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was growth hormone treated children exceeded that of the controls by 0.65 SD score (about 4 cm). The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score (about 3 cm). Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders.

  16. Associations between the number of natural teeth in postmenopausal women and hormone replacement therapy.

    Science.gov (United States)

    Han, Kyungdo; Ko, Youngkyung; Park, Yong-Gyu; Park, Jun-Beom

    2016-12-01

    Increasing research suggests that periodontal status is associated with hormone replacement therapy in postmenopausal women. This study was performed to assess the relationship between the number of natural teeth and ever use of hormone replacement therapy in postmenopausal women using nationally representative Korean data. Data from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to a total of 4869 respondents over 19 years old who had gone through menopause and who had no missing data for the reproductive factors and outcome variables in that study. The total number of natural teeth was then calculated after excluding third molars. The time of day when tooth brushing was done was recorded as representative oral health behavior. Multiple logistic regression analyses were used to assess association between the number of natural teeth and the use of hormone replacement therapy. Among participants who had ever used hormone replacement therapy, the proportions (percentage and standard error) with no teeth, 1-9 teeth, 10-19 teeth, 20-27 teeth, and 28 teeth were 5.0±2.4%, 6.7±1.4%, 12.5±1.7%, 18.9±1.0%, and 20.7±1.6%, respectively (Preplacement therapy, after adjustments. The analysis revealed that the use of hormone replacement therapy by postmenopausal women showed positive effects for retention of natural teeth. Lack of hormone replacement therapy may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Preparation of slowly released male sex hormone drug by radiation polymerization technique and its evaluation in vivo

    International Nuclear Information System (INIS)

    Liu Rueizhi; Lei Shaoqiong; Li Ximing

    1992-01-01

    The radiation polymerization technique was used for immobilization testosterone propionate into crosslinked network of poly hydroxyethyl methacrylate to prepare slowly released male sex hormone drug which is used for testicular prosthesis. The testicular prosthesis was transplanted into the scrotum of male rabbit whose testes was excised 2 months before the transplantation. Then the level of male sex hormone in serum was measured by radioimmunoassay once a week after transplantation. The results of measurement in a period of 6 months were shown that the testicular prosthesis has a stable release of male sex hormone. The testosterone level in serum of the castrated male rabbits rises markedly and finally stabilizes at the level of 429 ± 36 ng/100 ml after transplantation. Macroscopic examination of biopsies taken from the tissues around the testicular prosthesis showed that tissue compatibility was revealed well

  18. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Directory of Open Access Journals (Sweden)

    Marco Antonio Botelho

    2014-02-01

    Full Text Available OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10% combined with estriol (0.1% + estradiol (0.25% for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05 after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

  19. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    International Nuclear Information System (INIS)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan; Almeida, Jackson Guedes; Quintans Junior, Lucindo

    2014-01-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  20. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan, E-mail: marcobotelho@pq.cnpq.br [Universidade Potiguar, Natal, RN (Brazil). Lab. de Nanotecnologia; Fechine, Pierre [Universidade Federal do Ceara (GQMAT/UFCE), Fortaleza, CE (Brazil). Dept. de Quimica Analitica. Grupo Avancado de Biomateriais em Quimica; Queiroz, Danilo Caldas de [Instituto Federal de Ciencia e Tecnologia (IFCT), Fortaleza, CE (Brazil). Lab. de Biotecnologia; Ruela, Ronaldo [Instituto de Biotecnologia Aplicada (INBIOS), Fortaleza, CE (Brazil); Almeida, Jackson Guedes [Universidade Federal do Vale de Sao Francisco (UNIVALE), Petrolina, PE (Brazil). Fac. de Ciencias Farmaceuticas; Quintans Junior, Lucindo [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Fisiologia

    2014-06-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  1. Lipoproteína a, aterosclerosis y terapia hormonal de reemplazo Lipoprotein a, atherosclerosis and replacement hormone therapy

    Directory of Open Access Journals (Sweden)

    Miguel Lugones Botell

    2005-08-01

    Full Text Available Se realizó una revisión sobre la lipoproteína plasmática, Lp(a, cuyo papel fisiológico es poco conocido. Se ha descrito una asociación entre las concentraciones aumentadas de Lp(a y el proceso aterosclerótico. Además, su exceso podría inducir una disminución de la actividad fibrinolítica y, por tanto, favorecer la trombosis. También analizamos la terapia hormonal de reemplazo. En relación con los efectos positivos, mejora los síntomas climatéricos y previene la osteoporosis, aunque entre los efectos adversos en las mujeres que la siguen, se ha descrito un ligero aumento del riesgo del tromboembolismo venoso, y más recientemente, en estudios realizados en EE.UU. en los años 2002 y 2004, en el ya conocido estudio (Women´s Health Initiative Study, se reportó mayor incidencia de eventos cardiovasculares para la terapia combinada con estrógenos conjugados equinos y medroxiprogesterona, y de stroke para la terapia estrogénica. Estos estudios pusieron en su lugar los efectos de esta terapia, que no es totalmente inocua. Se precisan estudios más amplios para definir el papel de la terapia hormonal de reemplazo y otras medidas terapéuticas sobre el sistema hemostático, el metabolismo lipídico y la enfermedad cardiovascular.A review of plasmatic lipoprotein, Lp(a, whose physiological role is little known, was made. An association between the augmented concentrations of Lp(a and the atherosclerotic proccess has been described. Besides, its excess may lead to a reduction of the fibrinolytic activity and, therefore, favor thrombosis. The replacement hormone therapy was also analyzed. In relation to its positive effects, it improves the climacteric symptoms and prevents osteoporosis. Among its adverse effects, it has been observed a mild increase of the risk for venous thromboembolism and, more recently, in the aleady known Women's Health Initiative Study, it was reported a higher incidence of cardiovascular events for the combined

  2. Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

    Science.gov (United States)

    Batailler, Martine; Caraty, Alain; Malpaux, Benoît; Tillet, Yves

    2004-01-01

    Background During the preovulatory surge of gonadotropin-releasing hormone (GnRH), a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase). The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia. Results The distribution of GnRH-containing neurons throughout the preoptic area around the vascular organ of the lamina terminalis was studied following visualisation using immunohistochemistry. No difference was observed in the staining intensity for GnRH between the different groups. Clusters of GnRH-containing neurons (defined as 2 or more neurons being observed in close contact) were more numerous during the late follicular phase (43 ± 7) than during the luteal phase (25 ± 6), and the percentage of clusters was higher during the beginning of the follicular phase than during the luteal phase. There was no difference in the number of labelled neurons in each group. Conclusions These results indicate that the morphological organization of the GnRH-containing neurons in ewes is modified during the follicular phase. This transitory re-organization may contribute to the putative synchronization of these neurons during the surge. The molecular signal inducing this plasticity has not yet been identified, but oestradiol might play an important role, since in sheep it is the only signal which initiates the GnRH preovulatory surge. PMID:15555074

  3. Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

    Directory of Open Access Journals (Sweden)

    Malpaux Benoît

    2004-11-01

    Full Text Available Abstract Background During the preovulatory surge of gonadotropin-releasing hormone (GnRH, a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase. The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia. Results The distribution of GnRH-containing neurons throughout the preoptic area around the vascular organ of the lamina terminalis was studied following visualisation using immunohistochemistry. No difference was observed in the staining intensity for GnRH between the different groups. Clusters of GnRH-containing neurons (defined as 2 or more neurons being observed in close contact were more numerous during the late follicular phase (43 ± 7 than during the luteal phase (25 ± 6, and the percentage of clusters was higher during the beginning of the follicular phase than during the luteal phase. There was no difference in the number of labelled neurons in each group. Conclusions These results indicate that the morphological organization of the GnRH-containing neurons in ewes is modified during the follicular phase. This transitory re-organization may contribute to the putative synchronization of these neurons during the surge. The molecular signal inducing this plasticity has not yet been identified, but oestradiol might play an important role, since in sheep it is the only signal which initiates the GnRH preovulatory surge.

  4. CORTICOTROPIN-RELEASING HORMONE MICROINFUSION IN THE CENTRAL AMYGDALA DIMINISHES A CARDIAC PARASYMPATHETIC OUTFLOW UNDER STRESS-FREE CONDITIONS

    NARCIS (Netherlands)

    WIERSMA, A; BOHUS, B; KOOLHAAS, JM

    1993-01-01

    The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of

  5. Differential contribution of CBP:CREB binding to corticotropin-releasing hormone expression in the infant and adult hypothalamus

    NARCIS (Netherlands)

    Cope, J.L.; Regev, L.; Chen, Y.; Korosi, A.; Rice, C.J.; Ji, S.; Rogge, G.A.; Wood, M.A.; Baram, T.Z.

    2014-01-01

    Corticotropin-releasing hormone (CRH) contributes crucially to the regulation of central and peripheral responses to stress. Because of the importance of a finely-tuned stress system, CRH expression is tightly regulated in an organ- and brain region-specific manner. Thus, in hypothalamus, CRH is

  6. Usefulness of MRI in evaluation of hormonal therapy for the ovarian chocolate cysts

    Energy Technology Data Exchange (ETDEWEB)

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kono, Michio; Yamasaki, Katsuhito

    1988-09-01

    We evaluated the diagnostic capability of MRI in ovarian chocolate cysts treated by Danazol (analogue of testosterone). Both inversion recovery as T1-weighted image and long TE and TR spin echo as T2-weighted image were performed before and during hormonal therapy. Temporal change of signal intensity and size was evaluated in three ovarian chocolate cysts (stage II: 2 cases, stage III: 1 case by Beecham classification, 1966) using the 0.15-T MR system. The high intense signal from all of the cysts was seen on both T1 and T2 weighted images before treatment. There was marked decrease in size of the chocolate cysts during hormonal therapy, and they were of considerably lower signal intensity than initially on T2-weighted image. We concluded that MRI was useful to evaluate hormonal therapy for ovarian chocolate cysts.

  7. The usefulness of MRI in evaluation of hormonal therapy for the ovarian chocolate cysts

    International Nuclear Information System (INIS)

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kono, Michio; Yamasaki, Katsuhito.

    1988-01-01

    We evaluated the diagnostic capability of MRI in ovarian chocolate cysts treated by Danazol (analogue of testosterone). Both inversion recovery as T1-weighted image and long TE and TR spin echo as T2-weighted image were performed before and during hormonal therapy. Temporal change of signal intensity and size was evaluated in three ovarian chocolate cysts (stage II: 2 cases, stage III: 1 case by Beecham classification, 1966) using the 0.15-T MR system. The high intense signal from all of the cysts was seen on both T1 and T2 weighted images before treatment. There was marked decrease in size of the chocolate cysts during hormonal therapy, and they were of considerably lower signal intensity than initially on T2-weighted image. We concluded that MRI was useful to evaluate hormonal therapy for ovarian chocolate cysts. (author)

  8. The effects of growth hormone deficiency and growth hormone replacement therapy on intellectual ability, personality and adjustment in children.

    Science.gov (United States)

    Puga González, B; Ferrández Longás, A; Oyarzábal, M; Nosas, R

    2010-06-01

    Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.

  9. Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders.

    Science.gov (United States)

    Contoreggi, Carlo; Rice, Kenner C; Chrousos, George

    2004-01-01

    Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of

  10. Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals.

    Science.gov (United States)

    Gorin-Lazard, Audrey; Baumstarck, Karine; Boyer, Laurent; Maquigneau, Aurélie; Penochet, Jean-Claude; Pringuey, Dominique; Albarel, Frédérique; Morange, Isabelle; Bonierbale, Mireille; Lançon, Christophe; Auquier, Pascal

    2013-11-01

    Few studies have assessed the role of cross-sex hormones on psychological outcomes during the period of hormonal therapy preceding sex reassignment surgery in transsexuals. The objective of this study was to assess the relationship between hormonal therapy, self-esteem, depression, quality of life (QoL), and global functioning. This study incorporated a cross-sectional design. The inclusion criteria were diagnosis of gender identity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) and inclusion in a standardized sex reassignment procedure. The outcome measures were self-esteem (Social Self-Esteem Inventory), mood (Beck Depression Inventory), QoL (Subjective Quality of Life Analysis), and global functioning (Global Assessment of Functioning). Sixty-seven consecutive individuals agreed to participate. Seventy-three percent received hormonal therapy. Hormonal therapy was an independent factor in greater self-esteem, less severe depression symptoms, and greater "psychological-like" dimensions of QoL. These findings should provide pertinent information for health care providers who consider this period as a crucial part of the global sex reassignment procedure.

  11. Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

    Science.gov (United States)

    Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

    2015-12-01

    Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

  12. Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release

    International Nuclear Information System (INIS)

    Mauras, N.; Blizzard, R.M.; Rogol, A.D.

    1989-01-01

    A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses

  13. Induction of spermatogenesis and fertility in hypogonadotropic azoospermic men by intravenous pulsatile gonadotropin-releasing hormone (GnRH).

    Science.gov (United States)

    Blumenfeld, Z; Makler, A; Frisch, L; Brandes, J M

    1988-06-01

    Gonadotropin-releasing hormone (GnRH) has only recently become a helpful tool in the medication of hypogonadotropic hypogonadism (HH). Two azoospermic patients with HH who had previously been treated with hCG/hMG because of delayed puberty and each of whom had fathered a child after previous gonadotropin therapy were referred due to secondary failure of hCG/hMG treatment to induce spermatogenesis and fertility. A pulse study where blood was drawn every 15 minutes for LH, FSH and PRL RIAs was performed in each patient, and afterwards a bolus of i.v. GnRH was injected to assess gonadotropin responsiveness. A portable GnRH pump was connected to each patient so that it administered 5-20 micrograms of GnRH i.v. every 89 minutes. Spermatogenesis was first detected after 42 and 78 days respectively in the 2 treated HH men and 4 1/2 months from the start of treatment their wives became pregnant. No thrombophlebitis or other complications of the i.v. therapy occurred. In the case of the first patient, the semen was washed and concentrated and intra-uterine inseminations were carried out in an attempt to shorten the time needed to achieve fertility. The first pregnancy was successfully terminated at 38 weeks with the delivery of 2 heterozygotic normal male babies. The second pregnancy ended in spontaneous delivery of a healthy female. We conclude that i.v. pulsatile, intermittent GnRH administration is a safe, efficient and highly successful means of treating azoospermic men with HH.

  14. Bioidentical hormone therapy: Nova Scotia pharmacists’ knowledge and beliefs

    OpenAIRE

    Whelan, Anne Marie; Thebeau, Jean-Pierre; Jurgens, Tannis M.; Hurst, Eileen

    2012-01-01

    Objectives: To investigate Nova Scotia (NS) pharmacists´ knowledge and beliefs regarding the use of bioidentical hormones (BHs) for the management of menopause related symptoms. Methods: Using Dillman´s tailored design methodology, an invitation to complete the web-based questionnaire was emailed to pharmacists in NS as part of the Dalhousie College of Pharmacy Continuing Pharmacy Education Department´s (CPE) weekly email update. Data was analyzed using descriptive statistics. Results: Of app...

  15. Treatment of idiopathic hypogonadotropic hypogonadism in men with luteinizing hormone-releasing hormone: a comparison of treatment with daily injections and with the pulsatile infusion pump.

    Science.gov (United States)

    Shargil, A A

    1987-03-01

    Thirty husbands in childless couples, aged 24 to 35 years, were treated with luteinizing hormone-releasing hormone (LH-RH) for idiopathic hypogonadotropic hypogonadism (IHH) of peripubertal (incomplete) type. They were azoospermic or oligospermic, with less than 1.5 X 10(6)/ml nonmotile spermatozoa. The diagnosis of IHH was based on clinical and laboratory features and testicular biopsy specimen study and was further supported by results of stimulation tests and gonadotropin-releasing hormone (GnRH) test. Two treatment modalities were used: subcutaneous injections of 500 micrograms LH-RH twice daily; and perpetual subcutaneous injection, via portable infusion pump, of 25 ng/kg LH-RH, at 90-minute intervals. Two patients required a short second period of pulsatile treatment to cause a second pregnancy of their spouses. The pump proved to yield better results, compared with intermittent injections, in respect to endocrine responses, spermatogenesis, and fertility capacity. Normal levels of luteinizing hormone and follicle-stimulating hormone were reached in 2 to 3 weeks and normal testosterone levels in 8 to 10 weeks from the start of treatment. Sperm counts rose to greater than 60 X 10(6)/ml viable spermatozoa with less than 15% of abnormal forms in 3 to 5 months, and the wives conceived. Of a total of 18 deliveries of healthy infants, 12 offspring were identified genetically with their fathers. Four women were still pregnant at the conclusion of the study. The pump was well tolerated, without special operational problems to the patients. Pulsatile treatment is therefore recommended in the treatment of well-diagnosed and carefully selected cases of incomplete IHH.

  16. The use of gonadotrophin-releasing hormone antagonists in polycystic ovarian disease.

    Science.gov (United States)

    Lubin, V; Charbonnel, B; Bouchard, P

    1998-12-01

    Polycystic ovarian disease (PCOD) is characterized by anovulation, eventually high luteinizing hormone (LH) levels, with increased LH pulse frequency, and hyperandrogenism. As the aetiology of the disease is still unknown, gonadotrophin-releasing hormone (GnRH) antagonists, competitive inhibitors of GnRH for its receptor, are interesting tools in order to study and treat the role of increased LH levels and pulse frequency in this disease. Their administration provokes a rapid decrease in bioactive and immunoactive LH followed by a slower decrease in follicle-stimulating hormone (FSH). In patients with PCOD, the suppression of gonadotrophin secretion eradicates the symptoms of the disease as long as the treatment lasts. Several authors have suggested that increased plasma LH levels have deleterious effects on the fertility of women with PCOD. Indeed, fewer spontaneous pregnancies with more miscarriages are observed when plasma LH levels are high. Assisted reproduction techniques such as in vitro fertilization (IVF) have provided other clues to the role of the LH secretory pattern in women with PCOD. The number of oocytes retrieved, the fertilization rate and the cleavage rate are lower in PCOD patients undergoing IVF and this is inversely correlated with FSH:LH ratio. These abnormalities are corrected when endogenous secretion of LH is suppressed. On the other hand, implantation and pregnancy rates after IVF are similar to those observed in control women. New GnRH antagonists are devoid of side effects and suppress LH secretion within a few hours without a flare-up effect. This action lasts for 10-100 hours. When GnRH antagonists are associated with i.v. pulsatile GnRH, this combination both suppresses the effect of endogenous GnRH and because of the competition for GnRH receptors restores a normal frequency of LH secretion. We have studied two women with PCOD, administering first 10 mg s.c. every 72 hours for 7 days of the GnRH antagonist Nal-Glu, then adding on

  17. Hormone Therapy in Breast Cancer Survivors and Those at High Risk for Breast Cancer.

    Science.gov (United States)

    Reid, Robert L

    2018-05-10

    Women and health care providers are often fearful of using hormone therapy to deal with distressing menopausal symptoms in circumstances where there is a perceived or real increased risk of breast cancer. This paper examines the evidence for and against hormone therapy use in 3 common clinical situations: the woman with a positive family history in a first-degree relative, the woman who has undergone risk-reducing salpingo-oophorectomy due to a known genetic mutation, and the woman in whom treatment of breast cancer has induced premature menopause.

  18. A cost-effectiveness analysis of hormone replacement therapy in the menopause.

    Science.gov (United States)

    Cheung, A P; Wren, B G

    1992-03-02

    To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. All women of age 50 in New South Wales, Australia (n = 27,021). The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone

  19. Effect of priming injections of luteinizing hormone-releasing hormone on spermiation and ovulation in Gϋnther's Toadlet, Pseudophryne guentheri

    Directory of Open Access Journals (Sweden)

    Silla Aimee J

    2011-05-01

    Full Text Available Abstract Background In the majority of vertebrates, gametogenesis and gamete-release depend on the pulsatile secretion of luteinizing hormone-releasing hormone (LHRH from the hypothalamus. Studies attempting to artificially stimulate ovulation and spermiation may benefit from mimicking the naturally episodic secretion of LHRH by administering priming injections of a synthetic analogue (LHRHa. This study investigated the impact of low-dose priming injections of LHRHa on gamete-release in the Australian toadlet Pseudophryne guentheri. Methods Toadlets were administered a single dose of two micrograms per. gram LHRHa without a priming injection (no priming, or preceded by one (one priming or two (two priming injections of 0.4 micrograms per. gram LHRHa. Spermiation responses were evaluated at 3, 7 and 12 hrs post hormone administration (PA, and sperm number and viability were quantified using fluorescent microscopy. Oocyte yields were evaluated by stripping females at 10-11 hrs PA. A sub-sample of twenty eggs per female was then fertilised (with sperm obtained from testis macerates and fertilisation success determined. Results No priming induced the release of the highest number of spermatozoa, with a step-wise decrease in the number of spermatozoa released in the one and two priming treatments respectively. Peak sperm-release occurred at 12 hrs PA for all priming treatments and there was no significant difference in sperm viability. Females in the control treatment failed to release oocytes, while those administered an ovulatory dose without priming exhibited a poor ovulatory response. The remaining two priming treatments (one and two priming successfully induced 100% of females to expel an entire clutch. Oocytes obtained from the no, or two priming treatments all failed to fertilise, however oocytes obtained from the one priming treatment displayed an average fertilisation success of 97%. Conclusion Spermiation was most effectively induced in

  20. Slipped Capital Femoral Epiphysis as a Complication of Growth Hormone Therapy

    Directory of Open Access Journals (Sweden)

    Shuo-Yu Wang

    2007-01-01

    Full Text Available Slipped capital femoral epiphysis (SCFE is a rare complication of growth hormone (GH therapy. Here, we report three patients who developed SCFE during GH therapy. The first two patients had hypopituitarism and had started GH therapy at the age of 15 years 6 months and 13 years 9 months, respectively. SCFE developed 4 years and 1 year after GH therapy, respectively. The third patient had Prader-Willi syndrome with obesity and hypogonadism and began GH therapy at the age of 12 years and 11 months. SCFE developed 2 months after starting GH therapy. Pain over the hip joints or over the knees is an early sign of SCFE. Despite recommendation, none of the three patients continued GH therapy. A high index of suspicion during GH therapy in patients at high risk of SCFE is important for early diagnosis and appropriate management. [J Formos Med Assoc 2007;106(2 Suppl:S46-S50

  1. Effects of graded doses of goitrin, a goitrogen in rapeseed, on synthesis and release of thyroid hormone in chicks

    International Nuclear Information System (INIS)

    Akiba, Yukio; Matsumoto, Tatsuro

    1977-01-01

    Intrathyroidal metabolism in synthesis and release of thyroid hormone was investigated in chicks administered three different levels of goitrin (0.0125, 0.025 and 0.05% in the diet) for 14 days. Thyroid glands were enlarged to 2-5 times as large as that of the control in proportion to the goitrin content of the diet. Typical high radioiodine uptake goiter was demonstrated in the goitrin-administered chicks. Total thyroid 125 I content increased about twice as much as that of the control in the goitrin-administered chicks though it was depressed in 0.0065% PUT-administered chicks. Decrease of plasma PB 125 I (approximately a half of the control) was ascertained by the estimation of plasma thyroxine by radiostereoassay. In the intrathyroidal metabolism of iodine, synthesis of iodothyronines and iodination of MIT were suppressed by goitrin, but monoiodination of tyrosine was rather accelerated. The elevated ratio of thyroid iodothyronines/plasma PBI (1.5-1.7 times as much as that of the control) reveals that the depression of plasma level of thyroid hormone is more striking than the decrease in thyroid hormone in the gland in the goitrin-administered chicks. It is, therefore, suggested that goitrin has inhibitory effects not only on the biosynthesis of thyroid hormone in the gland but also on the release of thyroid hormone from the gland. (auth.)

  2. Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice

    Science.gov (United States)

    Zhang, Rong; Asai, Masato; Mahoney, Carrie E; Joachim, Maria; Shen, Yuan; Gunner, Georgia; Majzoub, Joseph A

    2016-01-01

    A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, while extra-hypothalamic CRH plays a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma ACTH, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open field, elevated plus maze, holeboard, light-dark box, and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus, and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation. PMID:27595593

  3. Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study.

    Science.gov (United States)

    Gorin-Lazard, Audrey; Baumstarck, Karine; Boyer, Laurent; Maquigneau, Aurélie; Gebleux, Stéphanie; Penochet, Jean-Claude; Pringuey, Dominique; Albarel, Frédérique; Morange, Isabelle; Loundou, Anderson; Berbis, Julie; Auquier, Pascal; Lançon, Christophe; Bonierbale, Mireille

    2012-02-01

    Although the impact of sex reassignment surgery on the self-reported outcomes of transsexuals has been largely described, the data available regarding the impact of hormone therapy on the daily lives of these individuals are scarce. The objectives of this study were to assess the relationship between hormonal therapy and the self-reported quality of life (QoL) in transsexuals while taking into account the key confounding factors and to compare the QoL levels between transsexuals who have, vs. those who have not, undergone cross-sex hormone therapy as well as between transsexuals and the general population (French age- and sex-matched controls). This study incorporated a cross-sectional design that was conducted in three psychiatric departments of public university teaching hospitals in France. The inclusion criteria were as follows: 18 years or older, diagnosis of gender identity disorder (302.85) according to the Diagnostic and Statistical Manual, fourth edition text revision (DSM-IV TR), inclusion in a standardized sex reassignment procedure following the agreement of a multidisciplinary team, and pre-sex reassignment surgery. QoL was assessed using the Short Form 36 (SF-36). The mean age of the total sample was 34.7 years, and the sex ratio was 1:1. Forty-four (72.1%) of the participants received hormonal therapy. Hormonal therapy and depression were independent predictive factors of the SF-36 mental composite score. Hormonal therapy was significantly associated with a higher QoL, while depression was significantly associated with a lower QoL. Transsexuals' QoL, independently of hormonal status, did not differ from the French age- and sex-matched controls except for two subscales of the SF-36 questionnaire: role physical (lower scores in transsexuals) and general health (lower scores in controls). The present study suggests a positive effect of hormone therapy on transsexuals' QoL after accounting for confounding factors. These results will be useful for

  4. Biosynthesis and release of thyrotropin-releasing hormone immunoreactivity in rat pancreatic islets in organ culture. Effects of age, glucose, and streptozotocin

    DEFF Research Database (Denmark)

    Dolva, L O; Welinder, B S; Hanssen, K F

    1983-01-01

    Thyrotropin-releasing hormone immunoreactivity (TRH-IR) was measured in isolated islets and in medium from rat pancreatic islets maintained in organ culture. TRH-IR in methanol extracts of both islets and culture medium was eluted in the same position as synthetic TRH by ion-exchange and gel...... chromatography and exhibited dilution curves parallel with synthetic TRH in radioimmunoassay. [3H]Histidine was incorporated into a component that reacted with TRH antiserum and had the same retention time as synthetic TRH on reversed-phase high-performance liquid chromatography. A continuous release of TRH...

  5. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  6. Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development.

    Science.gov (United States)

    Miller, Nichol L G; Wevrick, Rachel; Mellon, Pamela L

    2009-01-15

    Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS.

  7. Necdin, a Prader–Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development

    Science.gov (United States)

    Miller, Nichol L.G.; Wevrick, Rachel; Mellon, Pamela L.

    2009-01-01

    Prader–Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia, obesity and hypogonadotrophic hypogonadism, all highly suggestive of hypothalamic dysfunction. The NDN gene, encoding the MAGE family protein, necdin, maps to the PWS chromosome region and is highly expressed in mature hypothalamic neurons. Adult mice lacking necdin have reduced numbers of gonadotropin-releasing hormone (GnRH) neurons, but the mechanism for this reduction is unknown. Herein, we show that, although necdin is not expressed in an immature, migratory GnRH neuronal cell line (GN11), high levels are present in a mature GnRH neuronal cell line (GT1-7). Furthermore, overexpression of necdin activates GnRH transcription through cis elements bound by the homeodomain repressor Msx that are located in the enhancer and promoter of the GnRH gene, and knock-down of necdin expression reduces GnRH gene expression. In fact, overexpression of Necdin relieves Msx repression of GnRH transcription through these elements and necdin co-immunoprecipitates with Msx from GnRH neuronal cells, indicating that necdin may activate GnRH gene expression by preventing repression of GnRH gene expression by Msx. Finally, necdin is necessary for generation of the full complement of GnRH neurons during mouse development and extension of GnRH axons to the median eminence. Together, these results indicate that lack of necdin during development likely contributes to the hypogonadotrophic hypogonadal phenotype in individuals with PWS. PMID:18930956

  8. The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy.

    Science.gov (United States)

    Grimm, Simone; Wirth, Katharina; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Dziobek, Isabel; Bajbouj, Malek; Aust, Sabine

    2017-06-30

    Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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.

  10. 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.

  11. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus.

    Science.gov (United States)

    Jeanneteau, Freddy D; Lambert, W Marcus; Ismaili, Naima; Bath, Kevin G; Lee, Francis S; Garabedian, Michael J; Chao, Moses V

    2012-01-24

    Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased expression of the glucocorticoid receptor (GR) has been documented. To investigate the role of the GR in CRH neurons, we have targeted the deletion of the GR, specifically in the parventricular nucleus. Impairment of GR function in the parventricular nucleus resulted in an enhancement of CRH expression and an up-regulation of hypothalamic levels of BDNF and disinhibition of the HPA axis. BDNF is a stress and activity-dependent factor involved in many activities modulated by the HPA axis. Significantly, ectopic expression of BDNF in vivo increased CRH, whereas reduced expression of BDNF, or its receptor TrkB, decreased CRH expression and normal HPA functions. We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.

  12. Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Borges Machado

    2010-01-01

    Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

  13. Gonadotropin-Releasing Hormone Modulates Vomeronasal Neuron Response to Male Salamander Pheromone

    Directory of Open Access Journals (Sweden)

    Celeste R. Wirsig-Wiechmann

    2012-01-01

    Full Text Available Electrophysiological studies have shown that gonadotropin-releasing hormone (GnRH modifies chemosensory neurons responses to odors. We have previously demonstrated that male Plethodon shermani pheromone stimulates vomeronasal neurons in the female conspecific. In the present study we used agmatine uptake as a relative measure of the effects of GnRH on this pheromone-induced neural activation of vomeronasal neurons. Whole male pheromone extract containing 3 millimolar agmatine with or without 10 micromolar GnRH was applied to the nasolabial groove of female salamanders for 45 minutes. Immunocytochemical procedures were conducted to visualize and quantify relative agmatine uptake as measured by labeling density of activated vomeronasal neurons. The relative number of labeled neurons did not differ between the two groups: pheromone alone or pheromone-GnRH. However, vomeronasal neurons exposed to pheromone-GnRH collectively demonstrated higher labeling intensity, as a percentage above background (75% as compared with neurons exposed to pheromone alone (63%, P < 0.018. Since the labeling intensity of agmatine within neurons signifies the relative activity levels of the neurons, these results suggest that GnRH increases the response of female vomeronasal neurons to male pheromone.

  14. Thyrotropin-Releasing Hormone (TRH) Promotes Wound Re-Epithelialisation in Frog and Human Skin

    Science.gov (United States)

    Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E.; Hardman, Matthew J.; Paus, Ralf

    2013-01-01

    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. PMID:24023889

  15. Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

    Science.gov (United States)

    Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

    1999-05-01

    Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

  16. Autoradiographic localization of thyrotropin releasing hormone (TRH) receptors in the central nervous system

    International Nuclear Information System (INIS)

    Manaker, S.

    1985-01-01

    Quantitative autoradiography was used to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat and human central nervous system (CNS). The binding of [ 3 H]-3-methyl-histidine 2 -TRH ([ 3 H]-MeTRH) to TRH receptors was saturable, of a high affinity (K/sub d/ = 5 nM), and specific for TRH analogs. Studies with neurotoxins ibotenic acid and 6-hydroxydopamine (6-OHDA) suggest that TRH receptors within the amygdala are predominantly located on cell bodies, and not nerve terminals. Finally, an examination was made of the concentrations of TRH receptors in spinal cords of patients with amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons located in Lamina IX. Large decreases in TRH receptors were noted in ALS spinal cords, when compared to non-neurological controls, probably reflecting the loss of motor neurons. In addition, decreases in the TRH receptor concentration of Lamina II were observed. This finding may reflect the sensitivity of neurons throughout the CNS to the pathophysiologic mechanisms of neuronal degeneration which cause ALS

  17. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation.

    Science.gov (United States)

    Henninge, John; Pepaj, Milaim; Hullstein, Ingunn; Hemmersbach, Peter

    2010-01-01

    Several peptide drugs are being manufactured illicitly, and in some cases they are being made available to the public before entering or completing clinical trials. At the request of Norwegian police and customs authorities, unknown pharmaceutical preparations suspected to contain peptide drugs are regularly subjected to analysis. In 2009, an unknown pharmaceutical preparation was submitted for analysis by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). The preparation was found to contain a 29 amino acid peptide with a C-terminal amide function. Based on the interpretation of mass spectrometric data, an amino acid sequence was proposed. The sequence is consistent with a peptide currently marketed under the name CJC-1295. CJC-1295 is a releasing factor for growth hormone and is therefore considered a Prohibited Substance under Section S2 of the WADA Prohibited List. This substance has potential performance-enhancing effects, it is readily available, and there is reason to believe that it is being used within the bodybuilding community. Copyright © 2010 John Wiley & Sons, Ltd.

  18. Radioimmunoassay of thyrotropin releasing hormone in human serum and its clinical application

    International Nuclear Information System (INIS)

    Zhao Zhiying; Liu Shizhen

    1995-01-01

    The study was aimed at investigating the relationship between the TRH level in peripheral blood and the physiological, pathophysiological variation of the hypothalamic-pituitary-thyroid axis, especially at studying the relationship between TRH level and various thyroid function states as well as its clinical significance. A highly sensitive, specific radioimmunoassay of the thyrotropin releasing hormone (TRH) has been developed in the laboratory using 125 I labeled anti-TRH antibodies. Blood samples were collected in tubes containing a mixture of 8-hydroxyquinoline sulfur, Tween 20 and EDTA-2NA(E). The sensitivity was 8.3% pmol/L, and the intra- and inter-assay coefficients of variation were 2.5%∼4.9% and 8.9%∼10.0% respectively. The recovery rate ranged from 92%∼105%. The TRH levels in sera of 80 normals and 324 patients with pituitary thyroid diseases were measured with this assay. The results show a significant decrease of TRH levels in hyperthyroid patients and increase in hypothyroid subjects. The TRH levels in patients with nodular goiter and cold nodules, pituitary dwarfism and pituitary tumours were not significantly different from those of the normal group. The results demonstrated that measurement of TRH level in peripheral blood is useful in investigating the physiological and pathophysiological status of the hypothalamic-pituitary-thyroid axis function and the change in TRH levels has close relations with the thyroid function

  19. Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity.

    Science.gov (United States)

    Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

    2015-06-21

    To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P 0.05). Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

  20. Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

    OpenAIRE

    Flavell, D M; Wells, T; Wells, S E; Carmignac, D F; Thomas, G B; Robinson, I C

    1996-01-01

    Expression of human growth hormone (hGH) was targeted to growth hormone-releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF-hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth-retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the...

  1. Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

    International Nuclear Information System (INIS)

    Beyer, David C.; McKeough, Timothy; Thomas, Theresa

    2005-01-01

    Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] 70 years (p = 0.0013), Gleason score ≥ 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers

  2. Release of the radioactive patient following radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Powers, J.; Cancer Board, A.

    2004-07-01

    Patients walk out of medical facilities containing as much as a complete therapeutic dose of radiation on a daily basis. This presents a significant challenge to the radiation protection community, as most patients have no prior education related to radiation and may not have the aptitude to assimilate such knowledge. In the case of targeted radiation therapy in which radionuclides are used to selectively target the cancer, patients are typically released only after adequate elimination and decay of the radionuclide administered. Established modalities of targeted radiotherapy include the use of iodine for thyroid cancer, strontium for bone pain, phosphorous for haematological diseases, 131I-mIBG for neuroblastoma, and most recently Y-90 labelled monoclonal antibodies for lymphoma. In the case of permanent implants, implants of encapsulated radioactive sources are left permanently in the tissues, thus patients are released containing their complete therapeutic dose. Isotopes used in permanent implants include I-125, Pd-103 and Au-198. Radiation safety considerations for both cases, the release of a patient who has received targeted radiotherapy, and the release of a patient who has received a permanent implant, will be discussed. A summary of applicable regulations will serve as a starting point for each of the following considerations; i) Security and source control ii) Instructions to patient and family members iii) Risk to the public As the incidence of cancer increases, and the popularity of targeted radiotherapy and permanent seed implants grows, the event of having an untrained person in possession of a therapeutic dose of radiation becomes more and more common. It is essential to stop and examine the risk of this practice, whether current strategies to reduce the risk to an acceptable level are indeed effective, and whether control over these sources is even feasible. (Author)

  3. Release of the radioactive patient following radiation therapy

    International Nuclear Information System (INIS)

    Powers, J.; Cancer Board, A.

    2004-01-01

    Patients walk out of medical facilities containing as much as a complete therapeutic dose of radiation on a daily basis. This presents a significant challenge to the radiation protection community, as most patients have no prior education related to radiation and may not have the aptitude to assimilate such knowledge. In the case of targeted radiation therapy in which radionuclides are used to selectively target the cancer, patients are typically released only after adequate elimination and decay of the radionuclide administered. Established modalities of targeted radiotherapy include the use of iodine for thyroid cancer, strontium for bone pain, phosphorous for haematological diseases, 131I-mIBG for neuroblastoma, and most recently Y-90 labelled monoclonal antibodies for lymphoma. In the case of permanent implants, implants of encapsulated radioactive sources are left permanently in the tissues, thus patients are released containing their complete therapeutic dose. Isotopes used in permanent implants include I-125, Pd-103 and Au-198. Radiation safety considerations for both cases, the release of a patient who has received targeted radiotherapy, and the release of a patient who has received a permanent implant, will be discussed. A summary of applicable regulations will serve as a starting point for each of the following considerations; i) Security and source control ii) Instructions to patient and family members iii) Risk to the public As the incidence of cancer increases, and the popularity of targeted radiotherapy and permanent seed implants grows, the event of having an untrained person in possession of a therapeutic dose of radiation becomes more and more common. It is essential to stop and examine the risk of this practice, whether current strategies to reduce the risk to an acceptable level are indeed effective, and whether control over these sources is even feasible. (Author)

  4. Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

    DEFF Research Database (Denmark)

    Birch-Johansen, Fatima; Jensen, Allan; Olesen, Anne Braae

    2012-01-01

    We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women.......We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women....

  5. The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women : a randomized controlled trial

    NARCIS (Netherlands)

    Hak, AE; Bak, AAA; Lindemans, J; Planellas, J; Bennink, HJTC; Hofman, A; Grobbee, DE; Witteman, JCM

    2001-01-01

    Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine

  6. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    Science.gov (United States)

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-10-01

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  7. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy

    DEFF Research Database (Denmark)

    Sørensen, M B; Rosenfalck, A M; Højgaard, L

    2001-01-01

    OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional ......, which in turn, prevents disease in the elderly....

  8. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  9. An automatic framework for assessing breast cancer risk due to various hormone replacement therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal; Brandt, Sami; Nielsen, Mads

    It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone(...

  10. Hormone replacement therapy: short-term versus long-term use.

    Science.gov (United States)

    Rousseau, Mary Ellen

    2002-01-01

    Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

  11. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Brandt, Sami; Nielsen, Mads

    Background: It is well known that Menopausal Hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998),...

  12. Effect of long-term Hormone Replacement Therapy on Plasma Homocysteine in Postmenopausal Women

    DEFF Research Database (Denmark)

    Madsen, Jonna S; Kristensen, Søren R; Klitgaard, Niels A

    2002-01-01

    hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate...

  13. Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy

    DEFF Research Database (Denmark)

    Lee, Peter A; Ross, Judith L; Pedersen, Birgitte Tønnes

    2015-01-01

    BACKGROUND: Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS...

  14. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  15. The association between early menopause and risk of ischaemic heart disease: Influence of Hormone Therapy

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen Christine Leth; Andersen, Zorana Jovanovic; Heitmann, Berit Lilienthal

    2006-01-01

    Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether...... HT reduces this risk associated with early menopause....

  16. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk

    DEFF Research Database (Denmark)

    Rudolph, Anja; Hein, Rebecca; Lindström, Sara

    2013-01-01

    Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...

  17. Carotid Artery Distensibility and Hormone Therapy and Menopause: The Los Angeles Atherosclerosis Study (LAAS)

    Science.gov (United States)

    Shufelt, Chrisandra; Elboudwarej, Omeed; Johnson, B. Delia; Mehta, Puja; Bittner, Vera; Braunstein, Glenn; Berga, Sarah; Stanczyk, Frank; Dwyer, Kathleen; Merz, C. Noel Bairey

    2015-01-01

    Objective Observational studies suggest that arterial distensibility decreases during menopause; however, the relation to hormone therapy use is controversial. We prospectively studied distensibility and hormone therapy use during different menopause stages. Methods 161 women between 42–61 years of age without cardiovascular disease had carotid artery measurements by ultrasound to calculate the distensibility index at baseline and 3 years later. Menopause stage was classified at each visit as premenopausal, perimenopausal, and postmenopausal. Over 3 years of prospective observation, women were classified as remaining premenopausal, remaining postmenopausal, or transitioning, defined as change from premenopausal-to-perimenopausal, premenopausal-to-postmenopausal, perimenopausal-to-perimenopausal, or perimenopausal-to-postmenopausal. Results Distensibility declined over time in all menopause stages (pmenopause transition is associated with reduced vascular compliance. Hormone therapy is associated with better arterial distensibility only during menopause transition. Additional prospective studies are needed to confirm these findings and to determine if hormone therapy use beyond menopause transition is related to distensibility. PMID:26308234

  18. Carotid artery distensibility and hormone therapy and menopause: the Los Angeles Atherosclerosis Study.

    Science.gov (United States)

    Shufelt, Chrisandra; Elboudwarej, Omeed; Johnson, B Delia; Mehta, Puja; Bittner, Vera; Braunstein, Glenn; Berga, Sarah; Stanczyk, Frank; Dwyer, Kathleen; Merz, C Noel Bairey

    2016-02-01

    Observational studies have suggested that arterial distensibility decreases during menopause; however, its relationship with hormone therapy use remains controversial. We prospectively studied distensibility and hormone therapy use at different menopause stages. One hundred sixty-one women (aged between 42 and 61 y) without cardiovascular disease underwent carotid artery measurements by ultrasound to calculate distensibility index at baseline and 3 years later. Menopause stage was classified at each visit as premenopausal, perimenopausal, and postmenopausal. Across 3 years of prospective observation, women were classified as remaining premenopausal, remaining postmenopausal, or transitioning (defined as change from premenopausal to perimenopausal, from premenopausal to postmenopausal, from perimenopausal to perimenopausal, or from perimenopausal to postmenopausal). Distensibility declined across time at all menopause stages (P menopausal transition is associated with reduced vascular compliance. Hormone therapy is associated with better arterial distensibility only during the menopausal transition. Additional prospective studies are needed to confirm these findings and to determine whether hormone therapy use beyond the menopausal transition is related to distensibility.

  19. Hormone therapy and risk of myocardial infarction: a national register study

    DEFF Research Database (Denmark)

    Nielsen, Lars Hougaard; Løkkegaard, Ellen Christine Leth; Andreasen, Anne Helms

    2008-01-01

    AIM: To assess the risk of myocardial infarction (MI) as a result of hormone therapy (HT), with focus on the influence of age, duration of HT, various regimens and routes, progestagen type, and oestrogen dose. METHODS AND RESULTS: All healthy Danish women (n = 698,098, aged 51-69) were followed d...

  20. Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma : Influence of Gonadal Hormone Exposure

    NARCIS (Netherlands)

    Krul, Inge M; Opstal-van Winden, Annemieke W J; Aleman, Berthe M P; Janus, Cécile P M; van Eggermond, Anna M; De Bruin, Marie L; Hauptmann, Michael; Krol, Augustinus D G; Schaapveld, Michael; Broeks, Annegien; Kooijman, Karen R; Fase, Sandra; Lybeert, Marnix L; Zijlstra, Josée M; van der Maazen, Richard W M; Kesminiene, Ausrele; Diallo, Ibrahima; de Vathaire, Florent; Russell, Nicola S; van Leeuwen, Flora E

    2017-01-01

    BACKGROUND: Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. METHODS: We conducted a nested case-control study

  1. Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency?

    NARCIS (Netherlands)

    ter Maaten, JC

    2000-01-01

    During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated

  2. Radiation therapy alone for growth hormone-producing pituitary adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Plataniotis, G.A.; Kouvaris, J.R.; Vlahos, L.; Papavasiliou, C. [Athens Univ. (Greece). Dept. of Radiology

    1998-09-01

    We present our experience in the treatment of growth hormone (GH)-producing pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients suffering from GH-secreting pituitary adenomas were treated with radiotherapy alone. Two bilateral opposing coaxial fields were used in 10 patients and in the remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2 Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was given using a cobalt unit. Four patients treated with somatostatin prior to and 14 patients treated after the end of radiotherapy experienced symptom relief for 6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%) patients. Whereas RT alone is effective in the treatment of microadenomas, this is not true for large infiltrative macroadenomas. (orig.)

  3. Radiation therapy alone for growth hormone-producing pituitary adenomas

    International Nuclear Information System (INIS)

    Plataniotis, G.A.; Kouvaris, J.R.; Vlahos, L.; Papavasiliou, C.

    1998-01-01

    We present our experience in the treatment of growth hormone (GH)-producing pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients suffering from GH-secreting pituitary adenomas were treated with radiotherapy alone. Two bilateral opposing coaxial fields were used in 10 patients and in the remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2 Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was given using a cobalt unit. Four patients treated with somatostatin prior to and 14 patients treated after the end of radiotherapy experienced symptom relief for 6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%) patients. Whereas RT alone is effective in the treatment of microadenomas, this is not true for large infiltrative macroadenomas. (orig.)

  4. Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

    Science.gov (United States)

    Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali

    2018-02-17

    Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

  5. Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy.

    Science.gov (United States)

    Khadilkar, Vaman; Phadke, Nikhil; Khatod, Kavita; Ekbote, Veena; Gupte, Supriya Phanse; Nadar, Ruchi; Khadilkar, Anuradha

    2017-05-24

    With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score imaging (MRI) brain scan was done in all. Genetic mutations were tested for in GH1, GHRH, LHX3, LHX4 and PROP1, POU1F1 and HESX1 genes. Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in the GH1 gene. In two children, one each had a mutation in PROP1 and LHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygous GH1 deletion than in children with no genetic defect. Response to GH at the end of 1 year was poor in children with the homozygous GH1 deletion as compared to those with GHRHR mutation or without a known mutation.

  6. Neoadjuvant hormonal therapy and external-beam radiotherapy versus external-beam irradiation alone for prostate cancer. A quality-of-life analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pinkawa, Michael; Piroth, Marc D.; Asadpour, Branka; Gagel, Bernd; Fischedick, Karin; Siluschek, Jaroslav; Kehl, Mareike; Krenkel, Barbara; Eble, Michael J. [RWTH Aachen (Germany). Dept. of Radiotherapy

    2009-02-15

    To evaluate the impact of neoadjuvant hormonal therapy (NHT) on quality of life after external-beam radiotherapy (EBRT) for prostate cancer. A group of 170 patients (85 with and 85 without NHT) has been surveyed prospectively before EBRT (70.2-72 Gy), at the last day of EBRT, a median time of 2 months and 15 months after EBRT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs with and without NHT (median treatment time of 3.5 months before EBRT) were matched according to the respective planning target volume and prostate volume. Before EBRT, significantly lower urinary function/bother, sexual function and hormonal function/bother scores were found for patients with NHT. More than 1 year after EBRT, only sexual function scores remained lower. In a multivariate analysis, NHT and adjuvant hormonal therapy (HT) versus NHT only (hazard ratio 14; 95% confidence interval 2.7-183; p = 0.02) and luteinizing hormone-releasing hormone (LHRH) agonists versus antiandrogens (hazard ratio 3.6; 95% confidence interval 1.1-12; p = 0.04) proved to be independent risk factors for long-term erectile dysfunction (no or very poor ability to have an erection). With the exception of sexual function (additional adjuvant HT and application of LHRH analog independently adverse), short-term NHT was not found to decrease quality of life after EBRT for prostate cancer. (orig.)

  7. Effect of aging on GHRF-induced growth hormone release from anterior pituitary cells in primary culture

    International Nuclear Information System (INIS)

    Spik, K.W.; Boyd, R.L.; Sonntag, W.E.

    1991-01-01

    Five criteria were developed to validate the primary cell culture model for comparison of GRF-induced release of growth hormone in pituitary tissue from aging animals. Pituitaries from young (5-mo), middle-aged (14-mo), and old (24-mo) male Fischer 344 rats were dispersed using either trypsin/trypsin inhibitor or dispase and compared with respect to the number of pituitary cells recovered, cell viability, 3H-leucine incorporation into total protein, time course for recovery of optimal response to GRF, and the dose-relationship for GRF-induced release of growth hormone 2, 4, and 6 days after dispersal. Results indicated that direct comparison of cellular responses between tissues from young, middle-aged, and old rats in primary cell culture is confounded by variations in time for recovery of optimal responses, the effects of the enzymes used for dispersal, and the methods used to express the data

  8. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  9. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

    OpenAIRE

    Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

    2004-01-01

    Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patient...

  10. Dual effect of melatonin on gonadotropin-releasing-hormone-induced Ca(2+) signaling in neonatal rat gonadotropes

    Czech Academy of Sciences Publication Activity Database

    Zemková, Hana; Vaněček, Jiří

    2001-01-01

    Roč. 74, č. 4 (2001), s. 262-269 ISSN 0028-3835 R&D Projects: GA ČR GA309/99/0213; GA ČR GA309/99/0215; GA AV ČR IAA5011103; GA AV ČR IAA5011105 Institutional research plan: CEZ:AV0Z5011922 Keywords : melatonin * gonadotropin-release hormone * calcium Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.144, year: 2001

  11. Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotropin-releasing hormone neuronal system of the rabbit

    OpenAIRE

    Wadas, B.C.; Hartshorn, C.A.; Aurand, E.R.; Palmer, J.S.; Roselli, C.E.; Noel, M.L.; Gore, A.C.; Veeramachaneni, D.N.R.; Tobet, S.A.

    2010-01-01

    Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive-gonadotropin-releasing hormone (ir-GnRH) neurons in the region of the organum vasculosum of the lamina terminalis (OVLT) and rostral preoptic area (rPOA) by postnatal week (PNW) 6. To further examine the disruption of GnRH neurons by fetal vinclozolin exposure, in the current study, pregnant rabbits were dosed orall...

  12. CHARACTERIZATION OF THE RECEPTOR FOR GONADOTROPIN-RELEASING HORMONE IN THE PITUITARY OF THE AFRICAN CATFISH, CLARIAS-GARIEPINUS

    NARCIS (Netherlands)

    de Leeuw, R.; Conn, P. M.; van't Veer, C.; Goos, H. J.; van Oordt, P. G.

    1988-01-01

    Receptors for gonadotropin-releasing hormone (GnRH) were characterized using a radioligand prepared from a superactive analog of salmon GnRH (sGnRH), D-Arg(6)-Pro(9)-sGnRH-NEt (sGnRHa). Binding of(125)I-sGnRHa to catfish pituitary membrane fractions reached equilibrium after 2 h incubation at 4°C.

  13. The lower expression of gonadotropin-releasing hormone receptor associated with poor prognosis in gastric cancer

    Science.gov (United States)

    Lu, Mingzhu; Zhu, Jing; Ling, Yang; Shi, Wenping; Zhang, Changsong; Wu, Haorong

    2015-01-01

    Aims: Expression of gonadotropin-releasing hormone receptor (GnRHR) has been demonstrated in a number of malignancies. The aim is to investigate the expression of GnRHR and prognosis in gastric cancer. Methods and materials: GnRHR mRNA was examined in tumor and non-tumor tissues from 48 gastric cancer patients by Real-time PCR. The GnRHR protein expression was performed by immunohistochemical analysis. Results: The expression of GnRHR mRNA was higher (mean ± SD, -10.06 ± 1.28) in gastric tumor tissues than matched non-tumor tissues (mean ± SD, -12.43 ± 1.33). GnRHR mRNA expression was associated with lymph node metastasis, distant metastasis, and TNM stage. We found the decreased expression of GnRHR mRNA were significantly correlated with poor overall survival (P = 0.003). Immunocytochemical staining of GnRHR in tumor tissues showed mainly weak staining (43.48%, 10/23) and moderate staining (21.74%, 5/23) in high GnRHR mRNA patients, and mainly negative staining in low GnRHR mRNA patients. And the staining of GnRHR was not detection in tumor tissues for more than half of gastric patients (52.08%, 25/48). These results implied that the loss of GnRHR protein could be a main event in gastric cancer. Conclusion: The GnRHR expression is very low in gastric cancer, and the loss of GnRHR expression could be a poor prognostic factor, which implied that GnRHR could play an important role in the development of gastric cancer. PMID:26550267

  14. Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice.

    Science.gov (United States)

    Vastagh, Csaba; Rodolosse, Annie; Solymosi, Norbert; Farkas, Imre; Auer, Herbert; Sárvári, Miklós; Liposits, Zsolt

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) neurons play a pivotal role in the regulation of the hypothalamic-pituitary gonadal axis in a sex-specific manner. We hypothesized that the differences seen in reproductive functions of males and females are associated with a sexually dimorphic gene expression profile of GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact metestrous female and male GnRH-green fluorescent protein transgenic mice. About 1,500 individual GnRH neurons from each sex were sampled with laser capture microdissection followed by whole-transcriptome amplification for gene expression profiling. Under stringent selection criteria (fold change >1.6, adjusted p value 0.01), Affymetrix Mouse Genome 430 PM array analysis identified 543 differentially expressed genes. Sexual dimorphism was most apparent in gene clusters associated with synaptic communication, signal transduction, cell adhesion, vesicular transport and cell metabolism. To validate microarray results, 57 genes were selected, and 91% of their differential expression was confirmed by real-time PCR. Similarly, 88% of microarray results were confirmed with PCR from independent samples obtained by patch pipette harvesting and pooling of 30 GnRH neurons from each sex. We found significant differences in the expression of genes involved in vesicle priming and docking (Syt1, Cplx1), GABAergic (Gabra3, Gabrb3, Gabrg2) and glutamatergic (Gria1, Grin1, Slc17a6) neurotransmission, peptide signaling (Sstr3, Npr2, Cxcr4) and the regulation of intracellular ion homeostasis (Cacna1, Cacnb1, Cacng5, Kcnq2, Kcnc1). The striking sexual dimorphism of the GnRH neuron transcriptome we report here contributes to a better understanding of the differences in cellular mechanisms of GnRH neurons in the two sexes. © 2015 S. Karger AG, Basel.

  15. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    Energy Technology Data Exchange (ETDEWEB)

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  16. Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

    Directory of Open Access Journals (Sweden)

    Ryo eNishiguchi

    2012-10-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is an evolutionarily conserved neuropeptide with 10 amino acid residues, of which several structural variants exist. A molecular form known as GnRH2 ([His5 Trp7 Tyr8]GnRH, also known as chicken GnRH II is widely distributed in vertebrates except for rodents, and has recently been implicated in the regulation of feeding behavior in goldfish. However, the influence of GnRH2 on feeding behavior in other fish has not yet been studied. In the present study, therefore, we investigated the role of GnRH2 in the regulation of feeding behavior in a zebrafish model, and examined its involvement in food intake after intracerebroventricular (ICV administration. ICV injection of GnRH2 at 0.1 and 1 pmol/g body weight (BW induced a marked decrease of food consumption in a dose-dependent manner during 30 min after feeding. Cumulative food intake was significantly decreased by ICV injection of GnRH2 at 1 pmol/g BW during the 30-min post-treatment observation period. The anorexigenic action of GnRH2 was completely blocked by treatment with the GnRH type I receptor antagonist Antide at 50 pmol/g BW. We also examined the effect of feeding condition on the expression level of the GnRH2 transcript in the hypothalamus. Levels of GnRH2 mRNA obtained from fish that had been provided excess food for 7 days were higher than those in fish that had been fed normally. These results suggest that, in zebrafish, GnRH2 acts as an anorexigenic factor, as is the case in goldfish.

  17. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    Science.gov (United States)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

    1998-01-01

    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  18. Bone loss in long-term suppressive therapy with thyroid hormone

    International Nuclear Information System (INIS)

    Firooznia, H.; Blum, M.; Golimbu, C.; Rafii, M.

    1987-01-01

    The trabecular bone density of the spine was measured with CT in 31 women, aged 39-79 years, who had received an average of 13.5 years of thyroid suppressive therapy. The spinal trabecular bone density values in 24 (77%), 18 (58%), and 13 subjects (42%) were respectively below the mean for healthy age-matched controls, the fifth percentile for healthy premenopausal women, and the fifth percentile for age-matched controls. Cortical and trabecular bone loss occurs in hyperthyroidism. Although the intent is not to cause hyperthyroidism in subjects on suppressive therapy, supraphysical doses of thyroid hormone are usually necessary for suppression of thyroid-stimulating hormone. In this study, bone loss was noted in these subjects. Because most of these patients are middle-aged or postmenopausal women, who are at risk for osteoporosis, it is important to be aware of the risk of additional bone loss induced by thyroid suppressive therapy in them

  19. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults

    Science.gov (United States)

    Beckwith, Noor; Reisner, Sari L.; Zaslow, Shayne; Mayer, Kenneth H.; Keuroghlian, Alex S.

    2017-01-01

    Abstract Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults. Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation. Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist. Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients. PMID:29159310

  20. Octopus gonadotrophin-releasing hormone: a multifunctional peptide in the endocrine and nervous systems of the cephalopod.

    Science.gov (United States)

    Minakata, H; Shigeno, S; Kano, N; Haraguchi, S; Osugi, T; Tsutsui, K

    2009-03-01

    The optic gland, which is analogous to the anterior pituitary in the context of gonadal maturation, is found on the upper posterior edge of the optic tract of the octopus Octopus vulgaris. In mature octopus, the optic glands enlarge and secrete a gonadotrophic hormone. A peptide with structural features similar to that of vertebrate gonadotrophin-releasing hormone (GnRH) was isolated from the brain of octopus and was named oct-GnRH. Oct-GnRH showed luteinising hormone-releasing activity in the anterior pituitary cells of the Japanese quail Coturnix coturnix. Oct-GnRH immunoreactive signals were observed in the glandular cells of the mature optic gland. Oct-GnRH stimulated the synthesis and release of sex steroids from the ovary and testis, and elicited contractions of the oviduct. Oct-GnRH receptor was expressed in the gonads and accessory organs, such as the oviduct and oviducal gland. These results suggest that oct-GnRH induces the gonadal maturation and oviposition by regulating sex steroidogenesis and a series of egg-laying behaviours via the oct-GnRH receptor. The distribution and expression of oct-GnRH in the central and peripheral nervous systems suggest that oct-GnRH acts as a multifunctional modulatory factor in feeding, memory processing, sensory, movement and autonomic functions.

  1. Promotion and marketing of bioidentical hormone therapy on the internet: a content analysis of websites.

    Science.gov (United States)

    Yuksel, Nese; Treseng, Laetitia; Malik, Bushra; Ogbogu, Ubaka

    2017-10-01

    To evaluate the quality of information presented and claims made on websites offering bioidentical hormone therapy (BHT) products or services. A quantitative content analysis was completed on 100 websites promoting or offering BHT products or services. Websites were identified through Google search engine from September to October 2013. Search terms included "bioidentical hormone therapy" or "bioidentical progesterone," accompanied by "purchase or buy," "service," or "doctors." The Brief DISCERN instrument was used to determine the quality of the health information. Websites were from Canada (59%), United States (38%), and other countries (3%). Almost half of the websites originated from medical clinics (47%), and healthcare professionals offering BHT services included physicians (50%), pharmacists (19%), and naturopaths (16%). Majority of websites promoted BHT as custom-compounded formulations (62%), with only 27% indicating that BHT is also commercially available. Websites overall claimed that BHT had less risk compared with conventional hormone therapy (62%). BHT was described as having less breast cancer risk (40%), whereas over a quarter of websites described BHT as "protective" for breast cancer. Websites mainly targeted women (99%), with males mentioned in 62% of websites. Product descriptors used to promote BHT included individualization (77%), natural (70%), hormone imbalance (56%), and antiaging (50%). The mean Brief DISCERN score was 15, indicating lower quality of information. Claims made about BHT on the internet are misleading and not consistent with current professional organizations' recommendations. Understanding how BHT may be promoted on the internet can help healthcare professionals when educating patients.

  2. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    Energy Technology Data Exchange (ETDEWEB)

    Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S. [Department of Radiology-JPP 3889, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52246 (United States); Luisiri, A. [Cardinal Glennon Children' s Hospital, St. Louis, Missouri (United States); Garibaldi, L.R. [Children' s Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey (United States); St. Barnabas Medical Center, Livingston, New Jersey (United States)

    2000-07-01

    Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

  3. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    International Nuclear Information System (INIS)

    Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S.; Luisiri, A.; Garibaldi, L.R.

    2000-01-01

    Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

  4. Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

    Science.gov (United States)

    Bokser, L; Szende, B; Schally, A V

    1990-06-01

    The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.

  5. Changes of the prescription of hormone therapy in menopausal women: An observational study in Taiwan

    Directory of Open Access Journals (Sweden)

    Hsiao Fei-Yuan

    2007-04-01

    Full Text Available Abstract Background To evaluate the impact of the 2002 Women's Health Initiative (WHI study results on the prescription of menopausal hormone therapy (MHT to treat menopause-related symptoms in Taiwan. Methods This retrospective study participant data collected from women interviewed in 2001 Taiwan's National Health Interview Survey (NHIS and the National Health Insurance (NHI outpatient claims for women being treated for menopause-related symptoms. We compared prescriptions made for MHI to women seeking outpatient treatment for menopause-related symptoms before and after the publication of the 2002 WHI to study its effect of prescription behavior in Taiwan. There was one dichotomous outcome variable, which was whether MHT was prescribed or not in an outpatient visit to treat menopause-related symptoms. Results Our study included 504 women 45 years old or above whose outpatient visits for menopause-related symptoms were covered by National Health Insurance in 2002. In total, these 504 women made 2549 outpatient visits to be treated for these symptoms. The proportion of outpatient visits in which MHT was prescribed dropped from 83.0% (n = 1,155 before WHI to 73.0% (n = 844 after WHI. We found a decrease in likelihood that women would be prescribed MHT for menopause-related symptoms after the release of the WHI report (OR = 0.36, 95%CI = 0.25 to 0.52, p Conclusion The WHI report caused a substantial decline in the use of MHT to treat menopause-related symptoms in Taiwan. It was found to exert most of its influence in patients with higher educations, physicians with specialties other than gynecologists and obstetricians, and academic medical centers.

  6. Tripeptide amide L-pyroglutamyl-histidyl-L-prolineamide (L-PHP-thyrotropin-releasing hormone, TRH) promotes insulin-producing cell proliferation.

    Science.gov (United States)

    Luo, LuGuang; Luo, John Z Q; Jackson, Ivor

    2013-02-01

    A very small tripeptide amide L-pyroglutamyl-L-histidyl-L-prolineamide (L-PHP, Thyrotropin-Releasing Hormone, TRH), was first identified in the brain hypothalamus area. Further studies found that L-PHP was expressed in pancreas. The biological role of pancreatic L-PHP is still not clear. Growing evidence indicates that L-PHP expression in the pancreas may play a pivotal role for pancreatic development in the early prenatal period. However, the role of L-PHP in adult pancreas still needs to be explored. L-PHP activation of pancreatic β cell Ca2+ flow and stimulation of β-cell insulin synthesis and release suggest that L-PHP involved in glucose metabolism may directly act on the β cell separate from any effects via the central nervous system (CNS). Knockout L-PHP animal models have shown that loss of L-PHP expression causes hyperglycemia, which cannot be reversed by administration of thyroid hormone, suggesting that the absence of L-PHP itself is the cause. L-PHP receptor type-1 has been identified in pancreas which provides a possibility for L-PHP autocrine and paracrine regulation in pancreatic function. During pancreatic damage in adult pancreas, L-PHP may protect beta cell from apoptosis and initiate its regeneration through signal pathways of growth hormone in β cells. L-PHP has recently been discovered to affect a broad array of gene expression in the pancreas including growth factor genes. Signal pathways linked between L-PHP and EGF receptor phosphorylation suggest that L-PHP may be an important factor for adult β-cell regeneration, which could involve adult stem cell differentiation. These effects suggest that L-PHP may benefit pancreatic β cells and diabetic therapy in clinic.

  7. Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

    Science.gov (United States)

    Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

    2009-07-15

    The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

  8. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    International Nuclear Information System (INIS)

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-01-01

    A sensitive and specific radioimmunoassay for [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp 6 ]LH-RH) was developed and used for following the rate of liberation of [D-Trp 6 ]LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against [D-Trp 6 ]LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of [D-Trp 6 ]LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of [D-Trp 6 ]LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 μg of the peptide, serum [D-Trp 6 ]LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of [D-Trp 6 ]LH-RH was followed. The improved batch of microcapsules of [D-Trp 6 ]LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection

  9. Non-invasive treatments of luteinizing hormone-releasing hormone for inducing spermiation in American (Bufo americanus) and Gulf Coast (Bufo valliceps) toads.

    Science.gov (United States)

    Rowson, Angela D.; Obringer, Amy R.; Roth, Terri L.

    2001-01-01

    As many as 20% of all assessed amphibian species are threatened with extinction, and captive breeding programs are becoming important components of conservation strategies for this taxon. For some species, exogenous hormone administration has been integrated into breeding protocols to improve propagation. However, most treatments are administered by an intraperitoneal injection that can be associated with some risks. The general goal of this study was to identify a non-invasive method of applying luteinizing hormone-releasing hormone (LHRH), which reliably induces sperm release in toads. Specific objectives were to 1) test the spermiation response after topical application of different LHRH doses to the abdominal seat region, 2) evaluate the effects of adding the absorption enhancers dimethyl sulfoxide (DMSO), acetone, and glyceryl monocaprylate (GMC) to the LHRH, 3) assess the spermiation response after oral delivery of LHRH in a mealworm vehicle, and 4) compare sperm characteristics and spermiation responses to treatments in two different toad species. Male American (n = 9) and Gulf Coast (n = 7) toads were rotated systematically through a series of treatments. Urine was collected and evaluated for the presence of sperm at 0, 3, 7, 12, and 24 hours post-treatment. There were no statistical differences in spermiation induction or sperm characteristics between American and Gulf Coast toads after the treatments. Oral administration of 100 &mgr;g LHRH was occasionally successful in inducing spermiation, but results appeared largely unreliable. Ventral dermal application of 100 or 10 &mgr;g LHRH in 40% DMSO were more effective (P Zoo Biol 20:63-74, 2001. Copyright 2001 Wiley-Liss, Inc.

  10. Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

    Directory of Open Access Journals (Sweden)

    Nathan W Kopper

    2008-10-01

    Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

  11. Effect of in ovo injection of corticotropin-releasing hormone on the timing of hatching in broiler chickens.

    Science.gov (United States)

    Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

    2017-09-01

    In chicken embryos, intravenous injection of corticotropin-releasing hormone (CRH) causes the release of both corticosteroids and thyroid hormones. These hormones initiate and enhance the hatching process, raising the possibility that CRH treatment of the late chicken embryo could accelerate hatching and/or decrease the spread of hatching. We performed a series of exploratory tests to investigate whether in ovo delivery methods of CRH other than intravenous injection that are more practical in a commercial setting, affect hatching time in broilers. Corticotropin-releasing hormone was injected into the air cell, albumen, or amniotic fluid of broiler breeder eggs, in the last week of embryonic development. Average incubation duration was significantly decreased by 22 h when 2 μg of CRH was injected into the air cell on embryonic day 18 (E18) of Cobb eggs. Acceleration of hatching (but only by 8 h) was also seen for Ross chicks when CRH was injected daily into the albumen between E10 and E18. However, repeats of both experiments did not show consistent effects of CRH on hatching time; in most experiments performed, CRH did not affect hatching time. We speculate that the effectiveness of CRH uptake via these delivery methods and/or the duration and magnitude of the thyroxine and corticosterone response to CRH is not sufficient to have a substantial effect on hatching time. We therefore conclude that in ovo CRH treatment does not seem a feasible option as a practical tool to increase hatchery productivity or to investigate the effects of CRH agonists and antagonists on hatching. © 2017 Poultry Science Association Inc.

  12. Hormone replacement therapy and risk of non-fatal stroke

    DEFF Research Database (Denmark)

    Pedersen, A T; Lidegaard, O; Kreiner, S

    1997-01-01

    haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement...... influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may...... to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years....

  13. Positive impact of hormone replacement therapy on the fibrinolytic system

    DEFF Research Database (Denmark)

    Madsen, J S; Kristensen, S R; Gram, J

    2003-01-01

    be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. Methods: Healthy postmenopausal women (n...... = 248) were randomized to HRT (n = 122) or no substitution (n = 126) 5 years prior to investigation. RESULTS: Significantly higher values of t-PA activity and lower values of PAI-1 activity and PAI-1 antigen were found in the HRT group compared with the control group. This effect was independent...... of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per...

  14. Editorial Foreword: Comments on "Growth hormone (GH-releasing hormone and GH secretagogues in normal aging" || FREE PAPER ||

    Directory of Open Access Journals (Sweden)

    Richard F Walker

    2008-03-01

    Full Text Available Richard F WalkerInternational Society for Applied Research in Aging (SARAThis issue of Clinical Interventions in Aging contains a quite interesting and informative article about a topic that is popular and also controversial among practitioners of age-management medicine. Appropriate to that controversy, Drs Hersch and Merriam (2008 have asked the question in the title of their paper, does the use of growth hormone secretagogues in age management medicine hold the promise of a fountain of youth, or that of a pool of Tantalus? While there is universal understanding of the fountain imagery, the meaning of the pool is perhaps less obvious. It derives, of course, from the Greek myth of Tantalus, who had both a hidden, divine sire and a mortal one. As the son of Zeus, he was uniquely favored among mortals and was invited to share the food of the gods. However, driven by pride, he shared the divine ambrosia with other mortals, and thus aroused the ire of the gods. As punishment, he was made to stand chin-deep in water with a variety of sweet-smelling and delicious fruit dangling just over his head. However, whenever he tried to drink or eat, the water would magically recede or the fruit would miraculously be lifted just out of his reach. Thus, it is that torment, through which something seems to be offered only to be withdrawn again, that has been called “tantalizing” in memory of its best known victim.

  15. Luteinizing hormone pulsatility in females following radiation therapy for central nervous system malignancies

    International Nuclear Information System (INIS)

    Brasacchio, R.A.; Constine, L.S.; Woolf, P.; Raubertas, R.F.; Veldhuis, J.D.; Muhs, A.G.

    1997-01-01

    Purpose: Females incidentally irradiated to the hypothalamic-pituitary axis (H/P-A) during radiation therapy (RT) for brain tumors may become oligoamenorrheic. We previously demonstrated that these women are hypoestrogenemic but frequently have near normal or only moderately decreased basal luteinizing hormone (LH) levels and maintain appropriate peak pituitary responses to exogenous gonadotropin releasing hormone (GnRH). We postulated that hypothalamic injury resulting in abnormal LH pulsatility could explain this complex of findings. This investigation intended to characterize this hypothalamic injury and test two potentially corrective pharmacologic interventions. Catecholamines (specifically dopamine) and opiates are known to suppress pituitary LH release through inhibition of the pituitary gonadotropes or of the GnRH neuronal terminals in the hypothalamus. Radiation-induced dysfunction of the catecholaminergic or opiate control mechanisms might translate into an increase in dopamine or opiate release or receptor responsiveness, which in turn would inhibit pulsatile gonadotropin secretion, leading to reduced LH pulsatility and to gonadal dysfunction. We therefore determined the pattern of LH release in normal controls and in patients, at baseline as well as after administration of the dopamine receptor antagonist metoclopramide (MCP), and the opiate-receptor antagonist naloxone (NAL). Methods: Patient eligibility criteria included RT to the H/P-A for a non-H/P-A CNS tumor, usually astrocytoma, with subsequent hypoestrogenemia and oligo-amenorrhea. Patients and normal volunteers were studied first under control conditions and then using MCP and NAL in a randomized cross-over manner at monthly intervals. Serum samples for LH determination were taken every 10 minutes for 12 hours during an overnight hospital stay. MCP (10 mg) was administered as an IV bolus every 4.5 hours, and NAL was administered as a continuous infusion (1.6 mg/hour). The following morning each

  16. Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles.

    Directory of Open Access Journals (Sweden)

    Adriane Fugh-Berman

    2011-03-01

    Full Text Available BACKGROUND: Even after the Women's Health Initiative (WHI found that the risks of menopausal hormone therapy (hormone therapy outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. METHODS AND FINDINGS: We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1 Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2 acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement

  17. Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles.

    Science.gov (United States)

    Fugh-Berman, Adriane; McDonald, Christina Pike; Bell, Alicia M; Bethards, Emily Catherine; Scialli, Anthony R

    2011-03-01

    Even after the Women's Health Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement for scientific accuracy (κ=0.57) and substantial

  18. Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals

    Directory of Open Access Journals (Sweden)

    Amy T. Desaulniers

    2017-12-01

    Full Text Available Gonadotropin-releasing hormone 1 (GnRH1 and its receptor (GnRHR1 drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2 and its receptor (GnRHR2 also exist in mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, signifying high selection pressure and a critical biological role. However, the GnRH2 gene is absent (e.g., rat or inactivated (e.g., cow and sheep in some species but retained in others (e.g., human, horse, and pig. Likewise, many species (e.g., human, chimpanzee, cow, and sheep retain the GnRHR2 gene but lack the appropriate coding sequence to produce a full-length protein due to gene coding errors; although production of GnRHR2 in humans remains controversial. Certain mammals lack the GnRHR2 gene (e.g., mouse or most exons entirely (e.g., rat. In contrast, old world monkeys, musk shrews, and pigs maintain the coding sequence required to produce a functional GnRHR2. Like GnRHR1, GnRHR2 is a 7-transmembrane, G protein-coupled receptor that interacts with Gαq/11 to mediate cell signaling. However, GnRHR2 retains a cytoplasmic tail and is only 40% homologous to GnRHR1. A role for GnRH2 and its receptor in mammals has been elusive, likely because common laboratory models lack both the ligand and receptor. Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from GnRH1/GnRHR1. Indeed, GnRH2 and its receptor are not physiological modulators of gonadotropin secretion in mammals. Instead, GnRH2 and GnRHR2 coordinate the interaction between nutritional status and sexual behavior in the female brain. Within peripheral tissues, GnRH2 and its receptor are novel regulators of reproductive organs. GnRH2 and GnRHR2 directly stimulate steroidogenesis within the porcine testis. In the female, GnRH2 and

  19. Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome.

    Directory of Open Access Journals (Sweden)

    Hazuki Komuro

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in the pathophysiology of irritable bowel syndrome (IBS and regulates the stress response through two CRH receptors (R1 and R2. Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436 and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220 were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017 and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS, and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710 and two SNPs (rs2284217 and rs2284220 in strong linkage disequilibrium (D' > 0.90. We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH

  20. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    Science.gov (United States)

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-04-25

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

  1. Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems

    International Nuclear Information System (INIS)

    Audhya, T.; Manzione, M.M.; Nakane, T.; Kanie, N.; Passarelli, J.; Russo, M.; Hollander, C.S.

    1985-01-01

    Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor [hpGRF(1-44)NH 2 ] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OH] were produced in rabbits. A subsequent booster injection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioimmunoassays for these peptides. The antibody to hpGRF(1-44)NH 2 is directed against the COOH-terminal region of the molecule, as shown by its cross reactivity with various hpGRF analogues. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 125 I-labeled tracer. There was no cross reactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays will serve as important tools for understanding the regulation of growth hormone secretion in both human and rat

  2. Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

    Science.gov (United States)

    Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

    2011-01-01

    There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

  3. Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; Jensen, Rikke Beck; Sundberg, Karin

    2014-01-01

    OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls.DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born...... in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown.CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19....

  4. Growth hormone therapy in a girl with Turner syndrome and diabetes type 1 - case report.

    Science.gov (United States)

    Obara-Moszynska, Monika; Banaszak, Magdalena; Niedziela, Marek

    2015-01-01

    The studies indicate the complex etiology of abnormal glucose metabolism in the Turner syndrome (TS). In the light of these carbohydrate disorders a therapy with recombinant growth hormone (rGH) in TS may be associated with complications, as growth hormone has a diabetogenic potential. Perinatal history is unknown since the patient was adopted at the age of 4 years. At 11 years old, due to typical phenotype, TS was diagnosed. The karyotype was 45,X[43]/46,X,i(X)(q10)[7]. At the same age, basing on laboratory results, insulin dependent diabetes was diagnosed and the conventional insulin therapy was initiated. During the hospitalization, at the age of 12 years, the patient was 123.5cm (-4.4SD). At the same age rGH tre-atment was initiated, with the dose 0.045 mg/kg/d. After 3 months of therapy the height velocity rose to 8.2 cm/ year. At the age of 13 years, substitution with 17β-estradiol was started. After 3 years and 4 months the growth hormone treatment was stopped because of poor height velocity. The final height of the patient was 140 cm (-4,OSD). Two years after the end of rGH treatment the height was 141.2 cm. After termination of rGH treatment the need for daily insulin dose decreased from 50-60U/d to 38-44U/d. The decision of rGH therapy in TS with diabetes is certainly difficult. While starting the growth hormone treatment the clinician must keep in mind the risk of metabolic complications, but also the awareness that gives the patient a chance to improve the final height. In terms of the proper psycho-emotional development the reduction of growth deficit is very important. © Polish Society for Pediatric Endocrinology and Diabetology.

  5. Risk of Breast Cancer in Relation to Combined Effects of Hormone Therapy, Body Mass Index, and Alcohol Use, by Hormone-receptor Status

    DEFF Research Database (Denmark)

    Hvidtfeldt, Ulla Arthur; Tjonneland, Anne; Keiding, Niels

    2015-01-01

    BACKGROUND: Alcohol consumption, increased body mass index (BMI), and hormone therapy are risk factors for postmenopausal breast cancer, but their combined effects are not well understood. Because hormone therapy is effective for the relief of menopausal symptoms, the identification of "high......,789 women ages 50+ years (study period 1981 to 2009). Information on risk factors was obtained in baseline questionnaires. We performed analyses using the Aalen additive hazards model. Serum estradiol and testosterone measurements were obtained in a subsample of approximately 1000 women. RESULTS: During 392...

  6. Synergistic effect of statins and postmenopausal hormone therapy in the prevention of skeletal fractures in elderly women.

    Science.gov (United States)

    Bakhireva, Ludmila N; Shainline, Michael R; Carter, Shelley; Robinson, Scott; Beaton, Sarah J; Nawarskas, James J; Gunter, Margaret J

    2010-09-01

    To examine the role of concurrent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on osteoporosis-related fractures. Case-control study. Data Source. Large integrated health plan in New Mexico. Patients. Case patients were 1001 women with incident fractures of the hip, wrist, forearm, or spine that occurred between January 1, 2000, and December 31, 2005, and controls were 2607 women without fractures during the same time frame; both groups were selected from the same population of women aged 50 years or older who utilized health plan services during the study time frame. Postmenopausal hormone therapy use was classified as "current" (12 mo before index date) or "never or past." The risk of fractures was ascertained among continuous (> or = 80% medication possession ratio during 12 mo before the index date) and current (3 mo before index date) statin users relative to patients without hyperlipidemia who did not use lipid-lowering drugs. The interaction between statins and hormone therapy was examined in multivariable logistic regression. The association between statin use and fractures was examined separately among current and never or past hormone therapy users after controlling for other risk factors. Nineteen percent of the study participants were current hormone therapy users; 9.5% were current and 4.8% were continuous statin users. No association between continuous statin use and fractures was observed among never or past hormone therapy users (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53-1.22). In contrast, a strong protective effect (OR 0.19, 95% CI 0.04-0.87) was observed among women who concurrently used statins and hormone therapy for 1 year, independent of age; corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index. Concurrent statin use and hormone therapy may have a synergistic

  7. Change in the use of hormone replacement therapy and the incidence of fracture in Oslo.

    Science.gov (United States)

    Meyer, H E; Lofthus, C M; Søgaard, A J; Falch, J A

    2009-05-01

    Fracture incidence in Oslo decreased from the 1970s to the 1990s in younger postmenopausal women, but not in older women or in men. Concurrently, hormone replacement therapy increased considerably. Using data from the Oslo Health Study, we estimated that roughly half the decline might be attributed hormone replacement therapy. Between the late 1970s and the late 1990s, the incidence of hip fracture and distal forearm fracture decreased in younger postmenopausal women in Oslo, but not in elderly women or in men. The purpose of this report is to evaluate whether the decreased incidence was coherent with trends in use of hormone replacement therapy (HRT). Data on estrogens were collected from official drug statistics, data on fractures from published studies and data on bone mineral density (BMD) from the Oslo Health Study. The sale of all estrogens increased 22 times from 1979 to 1999, and the sub-category estradiol combined with progestin increased 35 times. In the corresponding period the incidence of distal forearm fracture in women aged 50-64 years decreased by 33% and hip fracture by 39%. Based on differences in BMD between users and non-users of HRT, we estimated that up to half of this decline might be due to HRT. The reduction in fracture incidence in postmenopausal women in Oslo occurred in a period with a substantial increase in the use of HRT. Future surveillance will reveal whether the last years' decline in use of HRT will be translated into increasing fracture rates.

  8. Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study.

    Science.gov (United States)

    Warren, Michelle P; Brooks-Gunn, Jeanne; Fox, Richard P; Holderness, Claire C; Hyle, Emily P; Hamilton, William G; Hamilton, Linda

    2003-08-01

    To investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium. Clinical, placebo-controlled, randomized trial study.Healthy volunteers in an academic research environment. Fifty-five dancers (mean age: 22.0 +/- 4.6, age at menarche: 14.7 +/- 2.3 years), including 24 amenorrheics. Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day. Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine. Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization. These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea.

  9. Book review of "The estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins

    Science.gov (United States)

    Sonnenschein, Carlos

    2008-01-01

    "The Estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

  10. Book review of The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins

    Directory of Open Access Journals (Sweden)

    Sonnenschein Carlos

    2008-01-01

    Full Text Available Abstract The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

  11. Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Charlotte Guyader

    Full Text Available Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR antagonists (bicalutamide or flutamide. Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration, but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR as compared to continuous castration (RR(intermittent: 14.5, RR(complete blockade: 6.5 and 1.35. All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17 and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent

  12. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

    Directory of Open Access Journals (Sweden)

    Nikolaos Kyriakakis

    2017-01-01

    Full Text Available A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed.

  13. Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse.

    Science.gov (United States)

    Alba, Maria; Fintini, Danilo; Bowers, Cyril Y; Parlow, A F; Salvatori, Roberto

    2005-11-01

    Growth hormone (GH) secretagogues (GHS) stimulate GH secretion in vivo in humans and in animals. They act on the ghrelin receptor, expressed in both the hypothalamus and the pituitary. It is unknown whether GHSs act predominantly by increasing the release of hypothalamic GH-releasing hormone (GHRH) or by acting directly on the somatotroph cells. We studied whether a potent GHS could stimulate growth in the absence of endogenous GHRH. To this end, we used GHRH knockout (GHRH-KO) mice. These animals have proportionate dwarfism due to severe GH deficiency (GHD) and pituitary hypoplasia due to reduced somatotroph cell mass. We treated male GHRH-KO mice for 6 wk (from week 1 to week 7 of age) with GH-releasing peptide-2 (GHRP-2, 10 microg s.c. twice a day). Chronic treatment with GHRP-2 failed to stimulate somatotroph cell proliferation and GH secretion and to promote longitudinal growth. GHRP-2-treated mice showed an increase in total body weight compared with placebo-treated animals, due to worsening of the body composition alterations typical of GHD animals. These data demonstrate that GHRP-2 failed to reverse the severe GHD caused by lack of GHRH.

  14. Sexual dimorphism of gonadotropin-releasing hormone type-III (GnRH3) neurons and hormonal sex reversal of male reproductive behavior in Mozambique tilapia.

    Science.gov (United States)

    Kuramochi, Asami; Tsutiya, Atsuhiro; Kaneko, Toyoji; Ohtani-Kaneko, Ritsuko

    2011-10-01

    In tilapia, hormone treatment during the period of sexual differentiation can alter the phenotype of the gonads, indicating that endocrine factors can cause gonadal sex reversal. However, the endocrine mechanism underlying sex reversal of reproductive behaviors remains unsolved. In the present study, we detected sexual dimorphism of gonadotropin-releasing hormone type III (GnRH3) neurons in Mozambique tilapia Oreochromis mossambicus. Our immunohistochemical observations showed sex differences in the number of GnRH3 immunoreactive neurons in mature tilapia; males had a greater number of GnRH3 neurons in the terminal ganglion than females. Treatment with androgen (11-ketotestosterone (11-KT) or methyltestosterone), but not that with 17β-estradiol, increased the number of GnRH3 neurons in females to a level similar to that in males. Furthermore, male-specific nest-building behavior was induced in 70% of females treated with 11-KT within two weeks after the onset of the treatment. These results indicate androgen-dependent regulation of GnRH3 neurons and nest-building behavior, suggesting that GnRH3 is importantly involved in sex reversal of male-specific reproductive behavior.

  15. 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

  16. Plasma growth hormone response to human growth hormone releasing factor in rats administered with chlorpromazine and antiserum against somatostatin. Effects of hypo- and hyperthyroidism.

    Science.gov (United States)

    Wakabayashi, I; Tonegawa, Y; Ihara, T; Hattori, M; Shibasaki, T; Ling, N

    1985-10-01

    The effect of hypo- and hyperthyroidism on the plasma growth hormone (GH) response to synthetic human growth hormone releasing factor (GRF) was determined in conscious, freely moving rats pretreated with chlorpromazine and antiserum against somatostatin. Chlorpromazine plus somatostatin antiserum pretreated rats gave consistent response to GRF which was not observed in untreated rats. Chlorpromazine alone has no effect on GH secretion induced by GRF in rat pituitary monolayer culture. In rats made hypothyroid by thyroidectomy, both basal and peak plasma GH responses to a small (0.25 microgram/kg bw) and a moderate dose of GRF (1 microgram/kg bw) were significantly reduced as compared to controls. In rats made hyperthyroid by the administration of thyroxine, basal and peak plasma GH responses to a small but not to a moderate dose of GRF were significantly reduced as compared to controls. A reduced plasma GH response to a small dose of GRF was observed 8 days after the cessation of thyroxine administration. The pituitary GH reserve was markedly reduced in hypothyroid but not in hyperthyroid rats as compared to their respective controls. These results indicate that plasma GH response to GRF is reduced both in hypo- and hyperthyroidism. The mechanism involved in the phenomenon appears to be different between the two conditions.

  17. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Gonadotropin-Releasing Hormone Regulates Expression of the DNA Damage Repair Gene, Fanconi anemia A, in Pituitary Gonadotroph Cells1

    Science.gov (United States)

    Larder, Rachel; Chang, Lynda; Clinton, Michael; Brown, Pamela

    2007-01-01

    Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse LβT2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regulation of gene expression and differential display reverse transcription-polymerase chain reaction (RT-PCR) to identify and isolate hormonally induced changes. This approach identified Fanconi anemia a (Fanca), a gene implicated in DNA damage repair, as a differentially expressed transcript. Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility. We confirmed expression and hormonal regulation of Fanca mRNA by quantitative RT-PCR, which showed that GnRH induced a rapid, transient increase in Fanca mRNA. Fanca protein was also acutely upregulated after GnRH treatment of LβT2 cells. In addition, Fanca gene expression was confined to mature pituitary gonadotrophs and adult mouse pituitary and was not expressed in the immature αT3-1 gonadotroph cell line. Thus, this study extends the expression profile of Fanca into a highly specialized endocrine cell and demonstrates hormonal regulation of expression of the Fanca locus. We suggest that this regulatory mechanism may have a crucial role in the GnRH-response mechanism of mature gonadotrophs and perhaps the etiology of FA. PMID:15128600

  19. Gonadotropin-releasing hormone regulates expression of the DNA damage repair gene, Fanconi anemia A, in pituitary gonadotroph cells.

    Science.gov (United States)

    Larder, Rachel; Chang, Lynda; Clinton, Michael; Brown, Pamela

    2004-09-01

    Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse L beta T2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regulation of gene expression and differential display reverse transcription-polymerase chain reaction (RT-PCR) to identify and isolate hormonally induced changes. This approach identified Fanconi anemia a (Fanca), a gene implicated in DNA damage repair, as a differentially expressed transcript. Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility. We confirmed expression and hormonal regulation of Fanca mRNA by quantitative RT-PCR, which showed that GnRH induced a rapid, transient increase in Fanca mRNA. Fanca protein was also acutely upregulated after GnRH treatment of L beta T2 cells. In addition, Fanca gene expression was confined to mature pituitary gonadotrophs and adult mouse pituitary and was not expressed in the immature alpha T3-1 gonadotroph cell line. Thus, this study extends the expression profile of Fanca into a highly specialized endocrine cell and demonstrates hormonal regulation of expression of the Fanca locus. We suggest that this regulatory mechanism may have a crucial role in the GnRH-response mechanism of mature gonadotrophs and perhaps the etiology of FA.

  20. Building a better hormone therapy?: How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline

    Science.gov (United States)

    Frick, Karyn M.

    2012-01-01

    A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women. PMID:22289043

  1. Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Close Helen

    2012-05-01

    Full Text Available Abstract Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT. Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs were calculated for GORD and proton-pump inhibitor (PPI use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89. Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74. Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22. Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

  2. Shared decision making and patient choice for growth hormone therapy: current perspectives

    Directory of Open Access Journals (Sweden)

    George B

    2016-06-01

    Full Text Available Belinda George, Vageesh Ayyar Department of Endocrinology, St. John’s Medical College Hospital, Bangalore, Karnataka, India Abstract: Growth hormone has now been available in medical practice for close to 50 years. Its use has provided dramatic results in patients with growth hormone deficiency and it is associated with an overall favorable safety profile. Over the years, the utility of growth hormone has expanded to include treatment for short stature associated with conditions other than growth hormone deficiency, and this situation warrants greater involvement of the child and parents in the shared decision-making process. Shared decision making is in good conformance to the principle of informed consent, and it also improves the compliance and adherence to therapy as the patient fully understands the benefit and safety of the treatment. In the pediatric-care setting, the decision-making interactions usually occur between the health care provider, patient, and parents. The process may range from an autonomous decision-making pattern, where the patient or parents are fully responsible for the decision taken, to the paternalistic decision-making pattern, where the health care provider assumes full responsibility for the decision taken. However, the ideal situation is one where a truly shared decision-making process happens, in which the doctor and patient/parents work together to choose an evidence-based option, in line with the patient’s preferences and wishes. The limited data available on shared decision making with regard to growth hormone replacement, however, is not very encouraging and suggests that the actual involvement of the parents as perceived by them is less than optimal. Introduction of a simple structured model for a shared decision-making process that can be easily incorporated into clinical practice and familiarization of health care providers with the same is essential to improve our shared decision-making practices

  3. Prepubertal Development of Gonadotropin-Releasing Hormone Neuron Activity Is Altered by Sex, Age, and Prenatal Androgen Exposure.

    Science.gov (United States)

    Dulka, Eden A; Moenter, Suzanne M

    2017-11-01

    Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction though pulsatile hormone release. Disruption of GnRH release as measured via luteinizing hormone (LH) pulses occurs in polycystic ovary syndrome (PCOS), and in young hyperandrogenemic girls. In adult prenatally androgenized (PNA) mice, which exhibit many aspects of PCOS, increased LH is associated with increased GnRH neuron action potential firing. How GnRH neuron activity develops over the prepubertal period and whether this is altered by sex or prenatal androgen treatment are unknown. We hypothesized GnRH neurons are active before puberty and that this activity is sexually differentiated and altered by PNA. Dams were injected with dihydrotestosterone (DHT) on days 16 to 18 post copulation to generate PNA mice. Action potential firing of GFP-identified GnRH neurons in brain slices from 1-, 2-, 3-, and 4-week-old and adult mice was monitored. GnRH neurons were active at all ages tested. In control females, activity increased with age through 3 weeks, then decreased to adult levels. In contrast, activity did not change in PNA females and was reduced at 3 weeks. Activity was higher in control females than males from 2 to 3 weeks. PNA did not affect GnRH neuron firing rate in males at any age. Short-term action potential patterns were also affected by age and PNA treatment. GnRH neurons are thus typically more active during the prepubertal period than adulthood, and PNA reduces prepubertal activity in females. Prepubertal activity may play a role in establishing sexually differentiated neuronal networks upstream of GnRH neurons; androgen-induced changes during this time may contribute to the adult PNA, and possibly PCOS, phenotype. Copyright © 2017 Endocrine Society.

  4. Gene expression of thyrotropin- and corticotrophin-releasing hormones is regulated by environmental salinity in the euryhaline teleost Sparus aurata.

    Science.gov (United States)

    Ruiz-Jarabo, Ignacio; Martos-Sitcha, J A; Barragán-Méndez, C; Martínez-Rodríguez, G; Mancera, J M; Arjona, F J

    2018-04-01

    In euryhaline teleosts, the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-interrenal axes (HPT and HPI, respectively) are regulated in response to environmental stimuli such as salinity changes. However, the molecular players participating in this physiological process in the gilthead seabream (Sparus aurata), a species of high value for aquaculture, are still not identified and/or fully characterized in terms of gene expression regulation. In this sense, this study identifies and isolates the thyrotropin-releasing hormone (trh) mRNA sequence from S. aurata, encoding prepro-Trh, the putative factor initiating the HPT cascade. In addition, the regulation of trh expression and of key brain genes in the HPI axis, i.e., corticotrophin-releasing hormone (crh) and corticotrophin-releasing hormone-binding protein (crhbp), was studied when the osmoregulatory status of S. aurata was challenged by exposure to different salinities. The deduced amino acid structure of trh showed 65-81% identity with its teleostean orthologs. Analysis of the tissue distribution of gene expression showed that trh mRNA is, though ubiquitously expressed, mainly found in brain. Subsequently, regulation of gene expression of trh, crh, and crhbp was characterized in fish acclimated to 5-, 15-, 40-, and 55-ppt salinities. In this regard, the brain gene expression pattern of trh mRNA was similar to that found for the crh gene, showing an upregulation of gene expression in seabream acclimated to the highest salinity tested. Conversely, crhbp did not change in any of the groups tested. Our results suggest that Trh and Crh play an important role in the acclimation of S. aurata to hypersaline environments.

  5. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    Science.gov (United States)

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  6. Corticotropin-releasing hormone and mast cells in the regulation of mucosal barrier function in the human colon.

    Science.gov (United States)

    Wallon, Conny; Söderholm, Johan D

    2009-05-01

    Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

  7. Molecular and functional characterization of a novel gonadotropin-releasing-hormone receptor isolated from the common octopus (Octopus vulgaris)

    OpenAIRE

    Kanda, Atsuhiro; Takahashi, Toshio; Satake, Honoo; Minakata, Hiroyuki

    2006-01-01

    GnRH (gonadotropin-releasing hormone) plays a pivotal role in the regulation of reproduction in vertebrates through interaction with a specific receptor. Previously, we isolated a GnRH homo-logue, oct-GnRH, from the common octopus (Octopus vulgaris). In the present study, we have identified a GnRH receptor (oct-GnRHR) specific for oct-GnRH from Octopus brain. Oct-GnRHR includes domains and motifs typical of vertebrate GnRH receptors. The intron-inserted positions are conserved between oct-GnR...

  8. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    . This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese...... subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat...

  9. Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

    NARCIS (Netherlands)

    Moeniralam, H. S.; Endert, E.; van Lanschot, J. J.; Sauerwein, H. P.; Romijn, J. A.

    1997-01-01

    To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five

  10. Radiation therapy induced changes in male sex hormone levels in rectal cancer patients

    International Nuclear Information System (INIS)

    Dueland, Svein; Groenlie Guren, Marianne; Rune Olsen, Dag; Poulsen, Jan Peter; Magne Tveit, Kjell

    2003-01-01

    Background and purpose:To determine the effect of curative radiation therapy (46-50 Gy) on the sex hormone levels in male rectal cancer patients. Materials and methods:Twenty-five male rectal cancer patients (mean age 65 years), receiving pelvic radiation therapy (2 Gyx23-25 fractions in 5 weeks) were included. Serum testosterone, FSH and LH were determined before start of treatment, at the 10th and 25th fractions, and 4-6 weeks after completed radiotherapy. The testicular dose was determined by thermoluminescent dosimetry. Results:Five weeks of radiation therapy (46-50 Gy) resulted in a 100% increase in serum FSH, a 70% increase in LH, and a 25% reduction in testosterone levels. After treatment, 35% of the patients had serum testosterone levels below lower limit of reference. The mean radiation dose to the testicles was 8.4 Gy. A reduction in testosterone values was observed already after a mean dose of 3.3 Gy (10th fraction). Conclusion:Radiation therapy (46-50 Gy) for rectal cancer resulted in a significant increase in serum FSH and LH and a significant decrease in testosterone levels, indicating that sex hormone production is sensitive to radiation exposure in patients with a mean age of 65 years

  11. Comparison of low-normal and high-normal IGF-1 target levels during growth hormone replacement therapy : A randomized clinical trial in adult growth hormone deficiency

    NARCIS (Netherlands)

    van Bunderen, Christa C; Lips, Paul; Kramer, Mark H H; Drent, Madeleine L

    BACKGROUND: Current guidelines state that the goals of growth hormone (GH) therapy in adults should be an appropriate clinical response, avoidance of side effects, and an IGF-1 value within the age-adjusted reference range. There are no published studies on the target level for IGF-1 that offer

  12. The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial

    Directory of Open Access Journals (Sweden)

    Veerus Piret

    2012-04-01

    Full Text Available Abstract Background For postmenopausal women, the main reason to start hormone therapy (HT is to reduce menopausal symptoms and to improve quality of life (QOL. The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a randomised trial. A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy (EPHT trial in 1999–2001. Women were randomised to blind HT, open-label HT, placebo or non-treatment arm. After one year in the trial, a questionnaire was mailed and 1359 women (75% responded, 686 in the HT arms and 673 in the non-HT arms. Mean age at filling in the questionnaire was 59.8 years. The questionnaire included Women's Health Questionnaire (WHQ to assess menopause specific QOL of middle-aged women together with a 17-item questionnaire on symptoms related to menopause, a question about painful intercourse, and a question about women's self-rated health. Results After one year in the trial, fewer women in the HT arms reported hot flashes, trouble sleeping, and sweating on the symptom questionnaire. According to WHQ, women in the HT arms had fewer vasomotor symptoms, sleep problems, and problems with sexual behaviour, but more menstrual symptoms; HT had no effect on depression, somatic symptoms, memory, attractiveness, or anxiety. A smaller proportion of women reported painful intercourse in the HT arms. There were no significant differences between the trial arms in women’s self-rated subjective health. Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms, other than vasomotor symptoms, among postmenopausal women. WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women.

  13. 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)

  14. Optimal systemic therapy for premenopausal women with hormone receptor-positive breast cancer.

    Science.gov (United States)

    Jankowitz, Rachel C; McGuire, Kandace P; Davidson, Nancy E

    2013-08-01

    Although systemic therapy is one of the cornerstones of therapy for premenopausal women with early stage breast cancer, there remain many unknowns regarding its optimal use. By accident of clinical trial design, much clinical investigation in premenopausal women has focused on chemotherapy. More recently the value of endocrine therapy (tamoxifen and ovarian suppression/ablation via surgery, LHRH agonists, or chemotherapy-induced menopause) has become apparent, and some form of endocrine therapy is viewed as standard for virtually all premenopausal women with early stage invasive breast cancer that expresses estrogen and/or progesterone receptor. Critical open questions include type and duration of endocrine therapy and the development of prognostic/predictive markers to help identify patients who are likely to benefit from chemotherapy in addition to endocrine therapy. For some years, five years of tamoxifen has been viewed as the standard endocrine therapy for premenopausal hormone-responsive breast cancer, although the ATLAS trial suggests that an additional five years of tamoxifen can be considered. The MA17 trial also suggests that an additional five years of an aromatase inhibitor can be considered for women who become postmenopausal during tamoxifen therapy. Information about the value of ovarian suppression continues to emerge, most recently with the demonstration of excellent outcome with goserelin plus tamoxifen in the ABCSG12 trial. The SOFT and TEXT trials, whose accrual is now complete, should help to define optimal endocrine therapy. In addition, use of the 21-gene recurrence score assay may help to delineate the additional value of chemotherapy for patients with node-negative breast cancer, and its utility in the setting of women with 1-3 positive lymph nodes is under study in the RxPONDER trial. Nonetheless, the need for other predictive biomarkers to select appropriate therapy remains real. Finally, attention to long term benefits and side effects

  15. АBNORMAL UTERINE BLEEDING DURING МENOPAUSAL HORMONAL THERAPY

    Directory of Open Access Journals (Sweden)

    Ya. Z. Zaydieva

    2015-01-01

    Full Text Available Postmenopausal women using continuous combined estrogen/progestin therapy are likely to have irregular bleedings or spotting. Up to now, their causes remain unclear. Most investigators believe that a potential mechanism of abnormal bleedings during menopausal hormonal therapy could be a change in the ratio of pro- and anti-angiogenic factors, namely, of vascular endothelial growth factor to thrombospondin-1; alterations in metalloproteinases and their tissue inhibitors; changes in a tissue factor that is a mediator of endometrial hemostasis; as well as an increased number of endometrial leukocytes with predominance of uterine natural killer cells. As long as no link between bleeding discharge during continuous combined hormonal treatment and any of these  actors has been established, each and every of them is the subject of in vivo and in vitro investigations. At present, there are no  herapeutic methods to correct this complication of hormonal treatment. Patient monitoring to exclude neoplastic abnormalities in endometrium are of paramount importance.

  16. What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

    Directory of Open Access Journals (Sweden)

    Eli Marcelo Lakryc

    Full Text Available OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol, Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate and Group C received a placebo (control. The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels.

  17. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    International Nuclear Information System (INIS)

    Iwasawa, Toshihisa; Matsumoto, Hidetsugu

    1996-01-01

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  18. Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups.

    Science.gov (United States)

    Espeland, Mark A; Rapp, Stephen R; Manson, JoAnn E; Goveas, Joseph S; Shumaker, Sally A; Hayden, Kathleen M; Weitlauf, Julie C; Gaussoin, Sarah A; Baker, Laura D; Padula, Claudia B; Hou, Lifang; Resnick, Susan M

    2017-06-01

    Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age. Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos. Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase. CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    International Nuclear Information System (INIS)

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel

    2005-01-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term (≤6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment

  20. Effects of a gonadotropin-releasing hormone vaccine on ovarian cyclicity and uterine morphology of an Asian elephant (Elephas maximus).

    Science.gov (United States)

    Boedeker, Nancy C; Hayek, Lee-Ann C; Murray, Suzan; de Avila, David M; Brown, Janine L

    2012-09-01

    This report describes the successful use of a gonadotropin-releasing hormone (GnRH) vaccine to suppress ovarian steroidogenic activity and to treat hemorrhage and anemia associated with reproductive tract pathology in a 59-year-old Asian elephant (Elephas maximus). The Repro-BLOC GnRH vaccine was administered subcutaneously as a series of 4 boosters of increasing dose from 3 to 30 mg of recombinant ovalbumin-GnRH fusion protein given at variable intervals after initial vaccination with 3 mg protein. Efficacy was confirmed over a year after initial vaccination based on complete ovarian cycle suppression determined by serum progestagen analyses. Estrous cycle suppression was associated with a significant increase in GnRH antibody binding and subsequent decrease in serum luteinizing hormone and follicle-stimulating hormone concentrations. Ultrasonographic examinations of the reproductive tract documented a reduction in uterine size and vascularity after immunization. The hematocrit level normalized soon after the initial intrauterine hemorrhage, and no recurrence of anemia has been detected. No substantive adverse effects were associated with GnRH vaccination. The results indicate that GnRH vaccination in elephants shows potential for contraception and management of uterine pathology in older elephants.

  1. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic

    2004-01-01

    of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2......The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...

  2. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  3. Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

    Science.gov (United States)

    Mathew, Aju; Davidson, Nancy E

    2015-11-01

    Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Does growth hormone releasing factor desensitize the somatotroph? Interpretation of responses of growth hormone during and after 10-hour infusion of GRF 1-29 amide in man.

    Science.gov (United States)

    Davis, J R; Sheppard, M C; Shakespear, R A; Lynch, S S; Clayton, R N

    1986-02-01

    It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10-h infusion of the equipotent 1-29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1-29). Four normal adult males received an intravenous infusion of 1-29 GRF (1 microgram/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 micrograms intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0.5 mU/l) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/l) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 micrograms GRF bolus increased mean (+/- SEM) GH from 0.82 +/- 0.21 mU/l to a peak of 59.0 +/- 44.8 mU/l (P less than 0.002). Following 10-GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6.4 and 7.2 rising to peak values of 11.2 and 23.0 mU/l respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak. The loss of GRF responsiveness after GRF infusion may be due to 'desensitization'.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. The relationships among acculturation, biobehavioral risk, stress, corticotropin-releasing hormone, and poor birth outcomes in Hispanic women.

    Science.gov (United States)

    Ruiz, R Jeanne; Dolbier, Christyn L; Fleschler, Robin

    2006-01-01

    To determine the predictive ability of acculturation as an antecedent of stress, biobehavioral risk, corticotropin-releasing hormone levels, and poor birth outcomes in pregnant Hispanic women. A prospective, observational design with data collected at 22-25 weeks of gestation and at birth through medical record review. Public prenatal health clinics in south Texas serving low-income women. Self-identified Hispanic women who had singleton pregnancies, no major medical risk complications, and consented to answer questionnaires as well as a venipuncture and review of their prenatal and birth medical records. Gestational age, Apgar scores, length, weight, percentile size, and head circumference of the infant at birth. Significant differences were seen in infant birth weight, head circumference, and percentile size by acculturation. English acculturation predicted stress, corticotropin-releasing hormone, biobehavioral risk, and decreased gestational age at birth. Investigation must continue to understand the circumstances that give rise to the decline in birth outcomes observed in Hispanics with acculturation to the dominant English culture in the United States.

  6. Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review.

    Science.gov (United States)

    Streed, Carl G; Harfouch, Omar; Marvel, Francoise; Blumenthal, Roger S; Martin, Seth S; Mukherjee, Monica

    2017-08-15

    Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.

  7. Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

    Science.gov (United States)

    Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

    2016-11-01

    To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Comparative In Vitro Controlled Release Studies on the Chronobiotic Hormone Melatonin from Cyclodextrins-Containing Matrices and Cyclodextrin: Melatonin Complexes.

    Science.gov (United States)

    Vlachou, Marilena; Papamichael, Marianna; Siamidi, Angeliki; Fragouli, Irene; Afroudakis, Pandelis A; Kompogennitaki, Rodanthi; Dotsikas, Yannis

    2017-07-28

    A series of hydrophilic matrix tablets was prepared and tested with respect to their ability to release the hormone melatonin in a controlled manner, in order to alleviate sleep onset and sleep maintenance dysfunctions. Besides the active ingredient, the tablets were comprised of combinations of the following: HPMC K 15M, low viscosity sodium alginate, microcrystalline cellulose (Avicel PH 102), magnesium stearate, and the cyclodextrins, α-CD, β-CD, γ-CD, HP-β-CD, sulfated β-CD, HP-α-CD and HP-γ-CD, and MLT (guest):CD (host) complexes of the above cyclodextrins, in 1:1 ratio. The controlled release studies were conducted in two aqueous dissolution media at pH 1.2 and 7.4. The stoichiometry of the formed complexes was examined by applying the continuous variation method (Job plot), while the stability constants were calculated by monitoring the spectrophotometric properties of free and CD-encapsulated melatonin (UV-Vis). Host-guest interactions were studied by Nuclear Magnetic Resonance (NMR) spectroscopy. The dissolution data suggest that melatonin is released faster from the MLT:CD complexes than from the rest matrix systems. This enhancement in the dissolution rate and the % release of melatonin from the complexes is due to the increased solubility of the MLT:CD complexes.

  9. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    International Nuclear Information System (INIS)

    Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-01-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

  10. Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome.

    Science.gov (United States)

    Moore, Aleisha M; Prescott, Mel; Marshall, Christopher J; Yip, Siew Hoong; Campbell, Rebecca E

    2015-01-13

    Polycystic ovarian syndrome (PCOS), the leading cause of female infertility, is associated with an increase in luteinizing hormone (LH) pulse frequency, implicating abnormal steroid hormone feedback to gonadotropin-releasing hormone (GnRH) neurons. This study investigated whether modifications in the synaptically connected neuronal network of GnRH neurons could account for this pathology. The PCOS phenotype was induced in mice following prenatal androgen (PNA) exposure. Serial blood sampling confirmed that PNA elicits increased LH pulse frequency and impaired progesterone negative feedback in adult females, mimicking the neuroendocrine abnormalities of the clinical syndrome. Imaging of GnRH neurons revealed greater dendritic spine density that correlated with increased putative GABAergic but not glutamatergic inputs in PNA mice. Mapping of steroid hormone receptor expression revealed that PNA mice had 59% fewer progesterone receptor-expressing cells in the arcuate nucleus of the hypothalamus (ARN). To address whether increased GABA innervation to GnRH neurons originates in the ARN, a viral-mediated Cre-lox approach was taken to trace the projections of ARN GABA neurons in vivo. Remarkably, projections from ARN GABAergic neurons heavily contacted and even bundled with GnRH neuron dendrites, and the density of fibers apposing GnRH neurons was even greater in PNA mice (56%). Additionally, this ARN GABA population showed significantly less colocalization with progesterone receptor in PNA animals compared with controls. Together, these data describe a robust GABAergic circuit originating in the ARN that is enhanced in a model of PCOS and may underpin the neuroendocrine pathophysiology of the syndrome.

  11. Semi-quantitative ultrastructural analysis of the localization and neuropeptide content of gonadotropin releasing hormone nerve terminals in the median eminence throughout the estrous cycle of the rat.

    Science.gov (United States)

    Prevot, V; Dutoit, S; Croix, D; Tramu, G; Beauvillain, J C

    1998-05-01

    The ultrastructural appearance of gonadotropin releasing hormone-immunoreactive elements was studied in the external zone of the median eminence of adult female Wistar rats. On the one hand, the purpose of the study was to determine the distribution of gonadotropin releasing hormone terminals towards the parenchymatous basal lamina at the level of hypothalamo-hypophyseal portal vessels, throughout the estrous cycle. On the other hand, we have semi-quantified the gonadotropin releasing hormone content in nerve terminals or preterminals during this physiological condition. A morphometric study was coupled to a colloidal 15 mn gold postembedding immunocytochemistry procedure. Animals were killed at 09.00 on diestrus II, 0.900, 10.00, 13.00, 17.00 and 18.00 on proestrus and 09.00 on estrus (n = 4-8 rats/group). A preliminary light microscopic study was carried out to identify an antero-posterior part of median eminence strongly immunostained by anti-gonadotropin releasing hormone antibodies but which was, in addition, easily spotted. This last condition was necessary to make a good comparison between each animal. Contacts between gonadotropin releasing hormone nerve terminals and the basal lamina were observed only the day of proestrus. Such contacts, however, were rare and in the great majority of cases, gonadotropin releasing hormone terminals are separated from basal lamina by tanycytic end feet. The morphometric analysis showed no significant variation in average distance between gonadotropin releasing hormone terminals and capillaries throughout the estrous cycle. Consequently, it did not appear that a large neuroglial plasticity exists during the estrous cycle. However, the observation of contacts only on proestrus together with some ultrastructural images evoke the possibility of a slight plasticity. The semi-quantitative results show that the content of gonadotropin releasing hormone in the nerve endings presented two peaks on proestrus: one at 09.00 (23 +/- 5

  12. Development of new radioactive labelling methods (3H and 11C) in luteizing hormone (LH) and its releasing hormone (LRF). Study of physico-chemical properties of LRF by circular dichroism and emission spectroscopy

    International Nuclear Information System (INIS)

    Marche, Pierre.

    1975-01-01

    After a brief review of present knowledge on the hypothalamus-hypophysis this thesis falls into three parts. The first situates the peptide hormones studied in their biological context. Research on the radioactive labelling of hormonal peptides is dealt with in part two which includes, besides the application of already known tritiation methods to particular problems, the description of a new tritium labelling method and the use of carbon 11 for the kinetic distribution study of a hormone. Part three concerns the physico-chemical study of a hypothalamic hormone. As a contribution towards research on the hypophysary gonadotrophic function regulation, the work involved in all the above three sections was directed towards the luteinising hormone (LH) and its hypothalamic release factor (LRF). During the study of this latter the problem of peptides containing tryptophane arose and was consequently investigated [fr

  13. Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy

    International Nuclear Information System (INIS)

    Cheung, Rex; Kamat, Ashish M.; Crevoisier, Renaud de; Allen, Pamela K.; Lee, Andrew K.; Tucker, Susan L.; Pisters, Louis; Babaian, Richard J.; Kuban, Deborah

    2005-01-01

    Background: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. Patients and Methods: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. Results: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA ≤0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. Conclusion: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal

  14. Relationship between nitric oxide- and calcium-dependent signal transduction pathways in growth hormone release from dispersed goldfish pituitary cells.

    Science.gov (United States)

    Chang, John P; Sawisky, Grant R; Davis, Philip J; Pemberton, Joshua G; Rieger, Aja M; Barreda, Daniel R

    2014-09-15

    Nitric oxide (NO) and Ca(2+) are two of the many intracellular signal transduction pathways mediating the control of growth hormone (GH) secretion from somatotropes by neuroendocrine factors. We have previously shown that the NO donor sodium nitroprusside (SNP) elicits Ca(2+) signals in identified goldfish somatotropes. In this study, we examined the relationships between NO- and Ca(2+)-dependent signal transduction mechanisms in GH secretion from primary cultures of dispersed goldfish pituitary cells. Morphologically identified goldfish somatotropes stained positively for an NO-sensitive dye indicating they may be a source of NO production. In 2h static incubation experiments, GH release responses to the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) were attenuated by CoCl2, nifedipine, verapamil, TMB-8, BHQ, and KN62. In column perifusion experiments, the ability of SNP to induce GH release was impaired in the presence of TMB-8, BHQ, caffeine, and thapsigargin, but not ryanodine. Caffeine-elicited GH secretion was not affected by the NO scavenger PTIO. These results suggest that NO-stimulated GH release is dependent on extracellular Ca(2+) availability and voltage-sensitive Ca(2+) channels, as well as intracellular Ca(2+) store(s) that possess BHQ- and/or thapsigargin-inhibited sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases, as well as TMB-8- and/or caffeine-sensitive, but not ryanodine-sensitive, Ca(2+)-release channels. Calmodulin kinase-II also likely participates in NO-elicited GH secretion but caffeine-induced GH release is not upstream of NO production. These findings provide insights into how NO actions many integrate with Ca(2+)-dependent signalling mechanisms in goldfish somatotropes and how such interactions may participate in the GH-releasing actions of regulators that utilize both NO- and Ca(2+)-dependent transduction pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Effect of stage of development and sex on gonadotropin-releasing hormone secretion in in vitro hypothalamic perifusion.

    Science.gov (United States)

    Lacau-Mengido, I M; González Iglesias, A; Díaz-Torga, G; Thyssen-Cano, S; Libertun, C; Becú-Villalobos, D

    1998-04-01

    Marked sexual and ontogenic differences have been described in gonadotropin regulation in the rat. These could arise from events occurring both at the hypothalamic or hypophyseal levels. The present experiments were designed to evaluate the capacity of the hypothalamus in releasing GnRH in vitro, basally and in response to depolarization with KCl, during ontogeny in the rat. To that end we chose two well-defined developmental ages that differ markedly in sexual and ontogenic characteristics of gonadotropin regulation, 15 and 30 days. We compared GnRH release from hypothalami of females, neonatal androgenized females and males. Mediobasal hypothalami were perifused in vitro, and GnRH measured in the effluent. Basal secretion of the decapeptide increased with age in the three groups with no sexual differences encountered. When studying GnRH release induced by membrane depolarization, no differences within sex or age were encountered. On the other hand FSH serum levels decreased with age in females and increased in males, and in neonatal androgenized females followed a similar pattern to that of females. LH levels were higher in infantile females than in age-matched males or androgenized females. Such patterns of gonadotropin release were therefore not correlated to either basal or K+-induced GnRH release from the hypothalamus. We conclude that sexual and ontogenic differences in gonadotropin secretion in the developing rat are not dependent on the intrinsic capability of the hypothalamus to release GnRH in response to membrane depolarization. The hormonal differences observed during development and between sexes are probably related to differences in the sensitivity of the GnRH neuron to specific secretagogue and neurotransmitter regulation, and/or to differences in hypophyseal GnRH receptors and gonadotrope sensitivity.

  16. Compliance of patients concerning recommended radiotherapy in breast cancer. Association with recurrence, age, and hormonal therapy

    International Nuclear Information System (INIS)

    Winzer, K.J.; Gruber, C.; Badakhshi, H.; Charite Universitaetsmedizin Berlin; Hinkelbein, M.; Denkert, C.

    2012-01-01

    Background and purpose: In this study, we investigated how often guidelines for radiation therapy in patients with breast cancer are not complied with, which patient group is mostly affected, and how this influences local recurrence. Patients and methods: All patients (n = 1,903) diagnosed between November 2003 and December 2008 with primary invasive or intraductal breast cancer in the interdisciplinary breast center of the Charite Hospital Berlin were included and followed for a median 2.18 years. Results: Patients who, in contrast to the recommendation of the interdisciplinary tumor board, did not undergo postoperative radiation experienced a fivefold higher local recurrence rate (p < 0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5% in this group. The 5-year locoregional recurrence-free survival of patients following the recommendations was 93.3%. Guideline compliance was dependent on age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and increased diameter of the primary tumor. Multiple logistic regression analysis showed an association between compliance and age or hormonal therapy. Conclusion: In order to avoid local recurrence patients should be motivated to comply with guideline driven therapy. Since a higher number of local recurrences is observed in health services research compared to clinical research, studies on the value of adjuvant treatment following local recurrence should be performed. (orig.)

  17. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

    Directory of Open Access Journals (Sweden)

    Piotr Milecki

    2010-10-01

    Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

  18. A radioreceptor assay of luteinizing hormone-releasing hormone receptor and characterization of LHRH binding to pituitary receptors in Shao duck

    International Nuclear Information System (INIS)

    Yang Peixin; Wu Meiwen; Chen Ziyuan

    2000-01-01

    The properties of Shao duck pituitary luteinizing hormone-releasing hormone (LHRH) receptors were analyzed in pituitary membrane preparation and isolated pituitary cells prepared by enzymatic dispersion with collagenase and trypsin, by using a super-agonist analog of (D-Lys 6 ) LHRH. High binding of 125 I-(D-Lys 6 ) LHRH to 10 6 cultured cells of Shao duck was observed after a 90 minute incubation at 4 degree C, while binding was significantly reduced after a 24h incubation. Binding of the radioligand was a function of tissue concentration of Shao duck pituitary membrane preparation, with a positive correlation over the range of 1-2 pituitary per-tube. Specific binding for 125 I-(D-Lys 6 ) LHRH increased with the increase in the amount of 125 I-(D-Lys 6 ) LHRH. The Scatchard analysis of data revealed a linear relationship between the amount of specific binding and the ratio of specific binding to free 1 '2 5 I(D-Lys 6 )LHRH, indicating a single class of high affinity sites. Equilibrium dissociation constant (Kd) was 0.34 nM in pituitary membrane preparation and 0.43 nM in isolated pituitary cells. Both Kd values were near and the maximum binding capacity (B max ) was great in isolated cells, suggesting no significant loss of the LHRH receptor population caused by the enzymatic procedure employed for cell dispersion in the present study. Addition of 9D-Lys 6 ) LHRH displaced bound 125 I-(D-Lys 6 ) LHRH. These results demonstrated the presence and provided characterization of LHRH receptors in Shao duck pituitary

  19. Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) in the nervus terminalis and brain of the big brown bat, Eptesicus fuscus.

    Science.gov (United States)

    Oelschläger, H A; Northcutt, R G

    1992-01-15

    Little is known about the immunohistochemistry of the nervous system in bats. This is particularly true of the nervus terminalis, which exerts strong influence on the reproductive system during ontogeny and in the adult. Luteinizing hormone-releasing hormone (LHRH) was visualized immunocytochemically in the nervus terminalis and brain of juvenile and adult big brown bats (Eptesicus fuscus). The peripheral LHRH-immunoreactive (ir) cells and fibers (nervus terminalis) are dispersed along the basal surface of the forebrain from the olfactory bulbs to the prepiriform cortex and the interpeduncular fossa. A concentration of peripheral LHRH-ir perikarya and fibers was found at the caudalmost part of the olfactory bulbs, near the medioventral forebrain sulcus; obviously these cells mediate between the bulbs and the remaining forebrain. Within the central nervous system (CNS), LHRH-ir perikarya and fibers were distributed throughout the olfactory tubercle, diagonal band, preoptic area, suprachiasmatic and supraoptic nuclei, the bed nuclei of stria terminalis and stria medullaris, the anterior lateral and posterior hypothalamus, and the tuber cinereum. The highest concentration of cells was found within the arcuate nucleus. Fibers were most concentrated within the median eminence, infundibular stalk, and the medial habenula. The data obtained suggest that this distribution of LHRH immunoreactivity may be characteristic for microchiropteran (insectivorous) bats. The strong projections of LHRH-containing nuclei in the basal forebrain (including the arcuate nucleus) to the habenula, may indicate close functional contact between these brain areas via feedback loops, which could be important for the processing of thermal and other environmental stimuli correlated with hibernation.

  20. Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.

    Science.gov (United States)

    Liao, Fan; Zhang, Tony J; Mahan, Thomas E; Jiang, Hong; Holtzman, David M

    2015-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHR(lit/lit) mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHR(lit/lit) mice was significantly smaller than that in PS1APP/GHRHR(lit/+) mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition. Copyright © 2014

  1. Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement.

    Science.gov (United States)

    Grossman, David C; Curry, Susan J; Owens, Douglas K; Barry, Michael J; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phipps, Maureen G; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen

    2017-12-12

    Menopause occurs at a median age of 51.3 years, and the average US woman who reaches menopause is expected to live another 30 years. The prevalence and incidence of most chronic conditions, such as coronary heart disease, dementia, stroke, fractures, and breast cancer, increase with age; however, the excess risk for these conditions that can be attributed to menopause alone is uncertain. Since the publication of findings from the Women's Health Initiative that hormone therapy use is associated with serious adverse health effects in postmenopausal women, use of menopausal hormone therapy has declined. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on the use of menopausal hormone therapy for the primary prevention of chronic conditions. The USPSTF reviewed the evidence on the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal women and whether outcomes vary among women in different subgroups or by timing of intervention after menopause. The review did not address hormone therapy for preventing or treating menopausal symptoms. Although the use of hormone therapy to prevent chronic conditions in postmenopausal women is associated with some benefits, there are also well-documented harms. The USPSTF determined that the magnitude of both the benefits and the harms of hormone therapy in postmenopausal women is small to moderate. Therefore, the USPSTF concluded with moderate certainty that combined estrogen and progestin has no net benefit for the primary prevention of chronic conditions for most postmenopausal women with an intact uterus and that estrogen alone has no net benefit for the primary prevention of chronic conditions for most postmenopausal women who have had a hysterectomy. The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women. (D recommendation) The USPSTF

  2. Menopausia, hipertensión arterial y terapia de reemplazo hormonal Menopause, blood hypertension and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Daysi Navarro Despaigne

    2003-04-01

    Full Text Available Para evaluar la influencia de la terapia de reemplazo hormonal (THR sobre el síndrome climatérico (SC y los niveles de tensión arterial en mujeres posmenopáusicas con hipertensión arterial (HTA, se realizó un ensayo terapéutico abierto, el cual incluyó 45 mujeres no obesas con HTA ligera/moderada. En cada mujer se evaluó la evolución de los síntomas climatéricos y de los niveles de tensión arterial, así como los efectos indeseables a la THR. Como medicamento las pacientes recibieron Estradiol 2mg + Levonorgestrel 1 mg por día durante 12 meses. Durante la THR disminuyeron los síntomas climatéricos, en particular los vasomotores (de 86,6 a 10 % y los genitourinarios (de 56,7 a 15 %. En la totalidad de las mujeres existió estabilidad en los niveles de tensión arterial. En 5 mujeres hubo necesidad de incrementar la dosis de medicamentos antihipertensivos. En el resto esta se mantuvo o disminuyó. Como efectos indeseables se reportó sangramiento vaginal, mastodinia, cefalea, vasculitis e isquemia del quinto dedo del pie. Las dos últimas pacientes debieron suspender el tratamiento y se presentaron al sexto mes de haber iniciado la THR. En conclusión, en mujeres de edad mediana con hipertensión arterial la THR mejora el síndrome climatérico sin empeorar los niveles de tensión arterial.To evaluate the influence of hormone replacement therapy on the climateric syndrome (CS and the blood pressure values in postmenopausal women with hypertension, an open therapeutic assay was carried out, which included 45 non-obese women with slight/moderate hypertension. The course of the climateric symptoms and the blood pressure levels as well as the adverse effects of HRT were evaluated in every woman. The patients took Estradiol 2mg plus Levonorgestrel 1 mg per day for 12 months as drug therapy. During the application of the HRT, the climateric symptoms, particularly vasomotor (from 86,6 to 10% and genitourinary (from 56,7 to 15% decreased

  3. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  4. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

    Directory of Open Access Journals (Sweden)

    Ji Woo Lee

    2014-09-01

    Full Text Available PurposeLong-acting gonadotropin-releasing hormone agonists (GnRHa are commonly used to treat central precocious puberty (CPP in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.MethodsThis retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.ResultsSix serious side effects (0.9% were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621. Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.ConclusionSterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

  5. Influence of hormone substitution therapy on postmenopausal uterus; Einfluss einer Hormonsubstitution auf den postmenopausalen Uterus

    Energy Technology Data Exchange (ETDEWEB)

    Otte, A.; Ruedisueli, A.; Goetze, M.; Leibundgut, U.; Mueller-Brand, J. [Inst. fuer Nuklearmedizin, Kantonsspital, Universitaetskliniken, Basel (Switzerland); Nitzsche, E.U. [Abt. Nuklearmedizin, Radiologische Universitaetsklinik, Freiburg (Germany)

    1997-12-01

    In a 58-year-old postmenopausal woman blood flow and blood pool images of bone scintigraphy showed a focus of increased activity in the right pelvic region. Computed tomography and ultrasound exhibited no abnormalities in the abdomen; especially the uterus and ovaries were normal. Careful anamnestic evaluation revealed that the patient received a long-term peroral estrogen/gestagen replacement therapy for the prevention of osteoporosis, but did not have menstruation-like bleedings for the last twelve months of therapy. At time of admission, the patient was on day 25 of hormone replacement therapy, and the uterus wash, therefore, in a premenstrual stage. Hence, despite cessation of bleedings in postmenopausal women, one should think of hormone replacement therapy as an explanation for vascular pelvic tumors seen by the first two phases of bone scintigraphy, before further diagnostic steps are undertaken. (orig.) [Deutsch] Bei der Skelettszintigraphie einer 58jaehrigen postmenopausalen Frau erkannte man in der Perfusions- und Blood-pool-Phase einen unklaren Fokus erhoehter Aktivitaet im rechten Becken. Computertomographie und Sonographie des Abdomens, insbesondere des Uterus und der Ovarien, waren unauffaellig. Nach eingehender anamnestischer Befragung stellte sich heraus, dass die Patientin unter einer mehrjaehrigen peroralen Oestrogen-/Gestagen-Hormonsubstitutionstherapie zur Osteoporose-Prophylaxe stand, jedoch seit den letzten zwoelf Monaten der Therapie ueber keine menstruationsaehnlichen Abbruchblutungen mehr berichten konnte. Bei ihrer Zuweisung befand sich die Patientin am 25. Tag der Hormonsubstitutionstherapie und ihr Uterus somit in einem praemenstruellen Stadium. Trotz Ausbleibens der Blutung bei postmenopausalen Frauen sollte somit an die Moeglichkeit der Hormonsubstitution gedacht und danach gefragt werden, wenn in den ersten beiden Phasen der Skelettszintigraphie eine unklare, gut vaskularisierte Struktur im kleinen Becken gefunden wird, bevor weitere

  6. Changes in the thyroid hormone level and blood profile after radioiodine therapy in Graves' disease

    International Nuclear Information System (INIS)

    Ogbac, R.V.

    2007-01-01

    Full text: Exacerbation of hyperthyroidism has been reported to occur as early as 3 days after administration of radioiodine (I-131) therapy. The hematological effects of radioiodine also have been reported but mainly confined in thyroid cancer cases wherein high doses are administered. This study was undertaken to determine the possible acute changes in the thyroid hormone concentration and blood picture of patients one week after therapy. Twelve hyperthyroid patients (8 females, 4 males), with ages ranging from 27-56 years, were followed with measurements of serum thyroid hormone levels and blood profile a week after I-131 therapy. All patients were pretreated with antithyroid medications. Radioiodine doses given ranged from 8 mCi up to 16 mCi, all based from the computed dose of 160 uCi/g. Only two out of twelve (2/12) exhibited an increase in FT3 level. Two patients showed a decrease while the remaining 8 patients showed no significant difference. Six out of 12 (50%) exhibited an increase in FT4 level. Five patients showed a decrease while only one had no significant difference. Hematologically, there were 5/12, 1/12, 3/12, 5/12 and 1/12 patients who showed a decrease in hemoglobin, hematocrit, RBC, WBC and platelet counts, respectively. Four out of 12, 2/12, and 1/12 patients, however, showed an increase in hemoglobin, RBC and platelet, respectively. The rest exhibited no significant change. FT4 level was observed to be more affected than FT3 levels but there was no consistent pattern established. A significant decrease in WBC count was observed. Although a high percentage of decreased hemoglobin was noted, no pattern was established. Radioiodine therapy caused no significant increase of serum FT3 and FT4 concentrations in the majority of patients after one week of therapy. In the followup of patients, determination of complete blood count of patients is also important. (author)

  7. Human fear acquisition deficits in relation to genetic variants of the corticotropin releasing hormone receptor 1 and the serotonin transporter.

    Directory of Open Access Journals (Sweden)

    Ivo Heitland

    Full Text Available The ability to identify predictors of aversive events allows organisms to appropriately respond to these events, and failure to acquire these fear contingencies can lead to maladaptive contextual anxiety. Recently, preclinical studies demonstrated that the corticotropin-releasing factor and serotonin systems are interactively involved in adaptive fear acquisition. Here, 150 healthy medication-free human subjects completed a cue and context fear conditioning procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex (FPS was measured to assess both uninstructed fear acquisition and instructed fear expression. All participants were genotyped for polymorphisms located within regulatory regions of the corticotropin releasing hormone receptor 1 (CRHR1 - rs878886 and the serotonin transporter (5HTTLPR. These polymorphisms have previously been linked to panic disorder and anxious symptomology and personality, respectively. G-allele carriers of CRHR1 (rs878886 showed no acquisition of fear conditioned responses (FPS to the threat cue in the uninstructed phase, whereas fear acquisition was present in C/C homozygotes. Moreover, carrying the risk alleles of both rs878886 (G-allele and 5HTTLPR (short allele was associated with increased FPS to the threat context during this phase. After explicit instructions regarding the threat contingency were given, the cue FPS and context FPS normalized in all genotype groups. The present results indicate that genetic variability in the corticotropin-releasing hormone receptor 1, especially in interaction with the 5HTTLPR, is involved in the acquisition of fear in humans. This translates prior animal findings to the human realm.

  8. Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

    Science.gov (United States)

    Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

    2000-03-01

    Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

  9. Description of women's personality traits and psychological vulnerability prior to choosing hormone replacement therapy

    DEFF Research Database (Denmark)

    Loekkegaard, E; Eplov, L F; Køster, A

    2002-01-01

    INTRODUCTION: Data suggest that women using hormone replacement therapy (HRT) represent a special subgroup of the general population regarding, for instance, cardiovascular risk factors and education. OBJECTIVE: To analyse if women who choose HRT are characterised a priori by high neuroticism sco...... confounders. The study suggests that selection bias among women choosing HRT may also include personality traits....... included Eysencks personality questionnaire concerning intro/extroversion and neuroticism. At the age of 45, the re-examination of the women included a test for psychological vulnerability. The participants reported whether or not they used HRT at the age of 40, 45, 51 and 60 years. The analyses comprised...

  10. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

    2004-01-01

    was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases......Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...

  11. Synthesis and in vitro and in vivo activity of analogs of growth hormone-releasing hormone (GH-RH) with C-terminal agmatine.

    Science.gov (United States)

    Zarandi, M; Csernus, V; Bokser, L; Bajusz, S; Groot, K; Schally, A V

    1990-12-01

    In the search for more active analogs of human growth hormone-releasing hormone (GH-RH), 37 new compounds were synthesized by solid phase methodology, purified, and tested biologically. Most of the analogs contained a sequence of 27 amino acids and N-terminal desaminotyrosine (Dat) and C-terminal agmatine (Agm), which are not amino acids. In addition to Dat in position 1 and Agm in position 29, the majority of the analogs had Ala15 and Nle27 substitutions and one or more additional L- or D-amino acid modifications. [Dat1, Ala15, Nle27]GH-RH(1-28)Agm (MZ-2-51) was the most active analog. Its in vitro GH-releasing potency was 10.5 times higher than that of GH-RH(1-29)NH2 and in the i.v. in vivo assay, MZ-2-51 was 4-5 times more active than the standard. After s.c. administration to rats. MZ-2-51 showed an activity 34 times higher at 15 min and 179 times greater at 30 min than GH-RH(1-29)NH2 and also displayed a prolonged activity. D-Tyr10, D-Lys12, and D-Lys21 homologs of MZ-2-51 also showed enhanced activities. Thus, [Dat1, D-Tyr10, Ala15, Nle27]GH-RH(1-28)Agm (MZ-2-159), [Dat1, D-Lys12, Ala15, Nle27]GH-RH(1-28)AGM (MZ-2-57), and [Dat1, Ala15, D-Lys21, Nle27]GH-RH(1-28)Agm (MZ-2-75) were 4-6 times more active in vitro than GH-RH(1-29)NH2. In vivo, after i.v. administration, analog MZ-2-75 was equipotent and analogs MZ-2-159 and MZ-2-57 about twice as potent as the standard.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    International Nuclear Information System (INIS)

    Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

    1989-01-01

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

  13. Evaluation of the responsiveness of pituitary gland to thyrotropin releasing hormone (TRH) in rats in the period of 8:00 to 12:00 a.m

    International Nuclear Information System (INIS)

    Borghi, V.C.; Nicolau, W.; Bojarczuk, C.; Pieroni, R.R.

    1977-01-01

    The functional pituitary capacity for the secretion thyrotropin in rats, in relation to the period of time 8:00-12:00 a.m. was studied by means of the administration of synthetic TRH (thyrotropin releasing hormone). The highest pituitary response to the hypothalamic hormone attains its peak between 9:50 and 10:30 a.m., a time in which the gland denotes a high and practically constant level of TSH secretion [pt

  14. Elevation of plasma gonadotropin concentration in response to mammalian gonadotropin releasing hormone (GRH) treatment of the male brown trout as determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Crim, L.W.; Cluett, D.M.

    1974-01-01

    Rapid increase of the plasma gonadotropin concentration as measured by radioimmunoassay has been demonstrated in response to GRH treatment of the sexually mature male brown trout. Peak gonadotropin values were observed within 15 minutes of GRH treatment, however, the return to baseline values was prolonged compared with the mammalian response. These data support the concept that the brain, operating via releasing hormones, plays a role in the control of pituitary hormone secretion in fish

  15. [Significance of lateral release in the therapy of patellar chondromalacia].

    Science.gov (United States)

    Krüger, T; Göbel, F; Huschenbett, A; Hein, W

    2002-10-01

    A retrospective study was performed in 26 patients who underwent an operation for femoro-patellar pain due to a patellar chondromalacia with or without minor patellar dislocation/lateral pressure syndrome. The average age of the patients was 28.5 (15-39) years. 22 of the 26 patients revealed minor chondral damages of the stages 1 and 2 according to Outerbridge. In 12 patients ("lavage" group), an arthroscopic joint debridement only was carried out, while an additional open, lateral retinaculum release was made in 14 patients ("lateral release" group). The patella's distance of dislocation according to Hepp was reduced on an average of 3.0 (0-7) mm (p = 0.0019). The results of Bentley's score obtained during the follow-up interval on an average of 30.1 (9 to 60) months were almost identical for both groups. "Good" and "very good" results were achieved in the "lavage" group (83.3 %) and "lateral release" group (78.6 % of the patients). Lateral release should be used in cases of patellar decentration between 5 and 10 mm and adequate pain symptoms. The post-operative distance of dislocation should be less than 5 mm. Under such conditions and with minor chondral damage, a combined approach by using an arthroscopic joint debridement and open lateral release is promising to treat a patellar dislocation/lateral pressure syndrome.

  16. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  17. Influence of growth hormone therapy on selected dental and skeletal system parameters.

    Science.gov (United States)

    Partyka, Małgorzata; Chałas, Renata; Dunin-Wilczyńska, Izabella; Drohomyretska, Myroslava; Klatka, Maria

    2018-03-14

    Growth