Sample records for gonadotropin-releasing hormone analog

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

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


    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...... assembly for final review. If consensus could not be reached, conclusions were based on majority vote. All participants approved the final statement. CONCLUSIONS: The efficacy of gonadotropin-releasing hormone analogs in increasing adult height is undisputed only in early-onset (girls

  2. Final adult height of girls with central precocious puberty or early and fast puberty could be improved by treatment of gonadotropin-releasing hormone analogs



    Objective To assess the efficacy and impact factors of treatment with Gonadotropin-releasing hormone analogs(GnRHa) in central precocious puberty(CPP)or early and fast puberty(EFP)girls in a retrospective unicenter study

  3. Adult height in short normal girls treated with gonadotropin-releasing hormone analogs and growth hormone.

    Pasquino, A M; Pucarelli, I; Roggini, M; Segni, M


    Combined treatment with GH and GnRH analogs (GnRHa) has been proposed to improve final adult height in true precocious puberty, GH deficiency, and short normal subjects with early or normal timing of puberty with still controversial results. We treated 12 girls with idiopathic short stature and normal or early puberty with GH and GnRHa and followed them to adult height; 12 girls comparable for auxological and laboratory characteristics treated with GH alone served to better evaluate the efficacy of addition of GnRHa. At the start of combined treatment, the chronological age of the girls (CA; mean +/- SD) was 10.2 +/- 0.9 yr, bone age (BA) was 10.6 +/- 1.9 yr, height SD score for BA was - 1.81 +/- 0.8, PAH was 146.3 +/- 5.0 cm. PAH was significantly lower than target height (TH 152.7 +/- 3.6 cm; P < 0.005). GH was given at a dose of 0.3 mg/kg x week, sc, 6 days weekly, and GnRHa (depot-triptorelin) was given at a dose of 100 microg/kg every 21 days, im. The 12 girls were treated with GH alone at the same dose; at the start of therapy their CA was 10.7 +/- 1.0, BA was 10.1 +/- 1.4 yr, height SD score for BA was - 1.65 +/- 0.8, PAH was 145.6 +/- 4.4 cm, and TH was 155.8 +/- 4.6 cm. Pubertal Tanner stage in both groups was B2P2 or B3P3. LHRH test and pelvic ultrasound showed the beginning of puberty. The GH response to standard provocative tests was 10 g/L or more. The mean period of treatment was 4.6 +/- 1.7 yr in the group treated with GH plus GnRHa and 4.9 +/- 1.4 yr in the group treated with GH alone; both groups discontinued treatment at comparable CA and BA. Adult height was considered to be attained when growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients in the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than the pretreatment PAH (156.3 +/- 5.9 vs. 146.3 +/- 5 cm); the gain in centimeters calculated between pretreatment PAH and adult height was 10 +/- 2.9 cm, and 7 of 12 girls had a

  4. Treatment of idiopathic short stature: effects of gonadotropin-releasing hormone analogs, aromatase inhibitors and anabolic steroids.

    Dunkel, Leo


    Modulation of sex steroid action on the growth plate can, at least theoretically, increase adult height in children and adolescents with idiopathic short stature. Gonadotropin-releasing hormone (GnRH) analog therapy during adolescence has been shown effective in a placebo-controlled study, but to obtain clinically significant increases in adult height, the treatment duration must be lengthy (several years). Furthermore, such treatment seems to compromise bone health and, because of the resulting delay in pubertal development, likely has psychosocial consequences. Therefore, GnRH analogs are no longer recommended to augment height in adolescents with short stature and normally timed puberty. Aromatase inhibitors are probably more effective than GnRH analogs in promoting increased adult height in children with short stature and, unlike GnRH analogs, do not delay pubertal development in males. However, due to a dearth of safety data with aromatase inhibitors for the treatment of short stature, their use outside a research setting is currently not recommended. Positive effects of anabolic steroids on adult height have not been documented.

  5. Gonadotropin-Releasing Hormone Analog Cotreatment for the Preservation of Ovarian Function during Gonadotoxic Chemotherapy for Breast Cancer: A Meta-Analysis.

    Chuan Wang

    Full Text Available To determine by meta-analysis whether gonadotropin-releasing hormone analog (GnRHa cotreatment accompanying chemotherapy for breast cancer protects ovarian function.Randomized controlled trials (RCTs comparing GnRH cotreatment with chemotherapy alone in premenopausal women were collected by electronic and manual searches of Pubmed, MEDLINE (OVID, CENTRAL (The Coehrane Central Register of Controlled Trials, CBM, CNKI, VIP and Wanfang data bases. All the data was analyzed by Stata 11.2.Seven studies with a total of 677 participants met the inclusion criteria. The outcome of meta-analysis implied that, compared with adjuvant chemotherapy alone, the number of patients with resumption of spontaneous menstruation was statistically greater in the GnRH cotreatment patients (OR 2.83; 95% CI, 1.52-5.25.Evidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, producing higher rates of spontaneous resumption of menses.

  6. Gonadotropin-releasing hormone in the ovary.

    Metallinou, Chryssa; Asimakopoulos, Byron; Schröer, Andreas; Nikolettos, Nikos


    Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the physiology of reproduction in mammals. GnRH acts by binding to the GnRH receptor (GnRHR). In humans, only 1 conventional GnRH receptor subtype (type I GnRH receptor) has been found. In the human genome, 2 forms of GnRH have been identified, GnRH-I (mammal GnRH) and GnRH-II (chicken GnRH II). Both forms and their common receptor are expressed, apart from the hypothalamus, in various compartments of the human ovary. Gonadal steroids, gonadotropins, and GnRH itself controls the regulation of the GnRH/GnRHR system gene expression in the human ovary. The 2 types of GnRH acting paracrinally/autocrinally influence ovarian steroidogenesis, decrease the proliferation, and induce apoptosis of ovarian cells. In this review, the biology of GnRH/GnRHR system in humans, the potential roles of GnRH, and the direct effects of GnRH analogues in ovarian cells are discussed.

  7. Gonadotropin releasing hormone agonists: Expanding vistas

    Navneet Magon


    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.

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

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


    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.

  9. The use of the gonadotropin-releasing hormone analog deslorelin for short-term contraception in red pandas (Ailurus fulgens).

    Koeppel, Katja N; Barrows, Michelle; Visser, Katherine


    Red pandas (Ailurus fulgens) are threatened with extinction owing to habitat loss, exacerbated by their unique ecology and low fecundity. Regional breeding programs manage captive red panda populations. Recommendations not to breed may be made for various reasons, including genetic overrepresentation of certain individuals. No recommendations have been published on the use of contraception for red pandas. This article discusses the use of the GnRH analog deslorelin as a reversible method of contraception in both male and female pandas. The mean time from last contraception to conception was 3 years with a 4.6-mg deslorelin implant. The average dose of GnRH implant received was 1.09 mg/kg (range, 0.88-1.32). Males returned to breeding sooner than females. No reproductive side effects were noted with up to three consecutive annual GnRH implants.

  10. Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

    Haogang Xue; Chunying Yang; Xiaodong Ge; Weiqi Sun; Chun Li; Mingyu Qi


    Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kisspeptin antagonist peptide 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

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

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


    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.

  12. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

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


    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.......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....

  13. Optimizing subcutaneous injection of the gonadotropin-releasing hormone receptor antagonist degarelix.

    Barkin, Jack; Burton, Shelley; Lambert, Carole


    The gonadotropin-releasing hormone (GnRH) receptor antagonist degarelix has several unique characteristics compared to luteinizing hormone-releasing hormone (LHRH) analogs used in the management of prostate cancer. Notable differences of GnRH receptor antagonists include no flare reaction, and a more rapid suppression of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate-specific antigen (PSA) compared to LHRH analogs. Despite emerging evidence supporting the use of GnRH receptor antagonists over the more widely used LHRH analogs in the management of prostate cancer, physicians may be reluctant to prescribe degarelix. They may be concerned about patient complaints about injection-site reactions (ISRs). The subcutaneous injection of degarelix has been associated with a higher rate of ISRs compared with the intramuscular injections of LHRH analogs. This "How I Do It" article describes techniques and strategies that have been developed by physicians and nurses to reduce the discomfort associated with the subcutaneous delivery of degarelix.

  14. Metabolic Health in Short Children Born Small for Gestational Age Treated With Growth Hormone and Gonadotropin-Releasing Hormone Analog : Results of a Randomized, Dose-Response Trial

    van der Steen, Manouk; Lem, Annemieke J.; van der Kaay, Danielle C. M.; Bakker-van Waarde, Willie M.; van der Hulst, Flip J. P. C. M.; Neijens, Floor S.; Noordam, Cees; Odink, Roelof J.; Oostdijk, Wilma; Schroor, Eelco J.; Westerlaken, Ciska; Hokken-Koelega, Anita C. S.


    Context: Previously we showed that pubertal children born small for gestational age (SGA) with a poor adult height (AH) expectation can benefit from treatment with GH1 mg/m(2) per day (similar to 0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with a double GH

  15. Basic understanding of gonadotropin-releasing hormone-agonist triggering.

    Casper, Robert F


    A single bolus of human chorionic gonadotropin (hCG) at midcycle has been the gold standard for triggering final oocyte maturation and ovulation in assisted reproductive technology cycles. More recently, gonadotropin-releasing hormone (GnRH)-agonist (GnRH-a) triggering has been introduced. The GnRH-a trigger may allow a more physiologic surge of both luteinizing hormone (LH) and follicle-stimulating hormone, although whether the combined surge will result in improved oocyte and embryo quality remains to be seen. However, the short duration of the LH surge with the GnRH-a trigger (approximately 34 hours) has been shown to be beneficial for preventing ovarian hyperstimulation syndrome in GnRH antagonist in vitro fertilization (IVF) cycles when compared with the prolonged elevation of hCG (≥6 days) after exposure to an hCG bolus. This review discusses the physiologic basis for the use of a GnRH-a trigger in IVF cycles.

  16. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    Fergus Keane


    Full Text Available Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour.

  17. Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

    Haluk Kelestimur; Emine Kacar; Aysegul Uzun; Mete Ozcan; Selim Kutlu


    The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1–7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

  18. Development of gonadotropin-releasing hormone secretion and pituitary response.

    Glanowska, Katarzyna M; Burger, Laura L; Moenter, Suzanne M


    Acquisition of a mature pattern of gonadotropin-releasing hormone (GnRH) secretion from the CNS is a hallmark of the pubertal process. Little is known about GnRH release during sexual maturation, but it is assumed to be minimal before later stages of puberty. We studied spontaneous GnRH secretion in brain slices from male mice during perinatal and postnatal development using fast-scan cyclic voltammetry (FSCV) to detect directly the oxidation of secreted GnRH. There was good correspondence between the frequency of GnRH release detected by FSCV in the median eminence of slices from adults with previous reports of in vivo luteinizing hormone (LH) pulse frequency. The frequency of GnRH release in the late embryonic stage was surprisingly high, reaching a maximum in newborns and remaining elevated in 1-week-old animals despite low LH levels. Early high-frequency GnRH release was similar in wild-type and kisspeptin knock-out mice indicating that this release is independent of kisspeptin-mediated excitation. In vivo treatment with testosterone or in vitro treatment with gonadotropin-inhibitory hormone (GnIH) reduced GnRH release frequency in slices from 1-week-old mice. RF9, a putative GnIH antagonist, restored GnRH release in slices from testosterone-treated mice, suggesting that testosterone inhibition may be GnIH-dependent. At 2-3 weeks, GnRH release is suppressed before attaining adult patterns. Reduction in early life spontaneous GnRH release frequency coincides with the onset of the ability of exogenous GnRH to induce pituitary LH secretion. These findings suggest that lack of pituitary secretory response, not lack of GnRH release, initially blocks downstream activation of the reproductive system.

  19. Value of Urinary Gonadotropin during Gonadotropin - Releasing Hormone Analog Stimulation Testing in Monitoring Gonadotropin- Releasing Hormone Analog Therapy for Children%促性腺激素释放激素类似物激发试验尿检法对儿童促性腺激素释放激素类似物疗效的判断价值

    马亚萍; 徐庄剑; 张婷婷; 谢书艳; 王勍; 赵金玲


    Objective To determine whether noninvasive urinary gonadotropin( Ucn) following gonadotropin releasing hormone analog (GnRHa) stimulation testing can be used for monitoring GnRHa therapy for children. Methods Seventeen female cases who suffered with central precocious puberty were treated with Diphereline. Other 6 cases (4 males,2 females) with short stature of predicted adult height were treated with growth hormone co - treatment within Diphereline. GnRHa stimulation testing was performed a week before the therapy, and repeated 3 months after the therapy. The 3.5 h timed urine collections were obtained during the testing,as well as urine in 18 cases were collected the day before the testing. Luteinizing hormone ( LH) and follicle stimulating hormone ( FSH) were assayed by immunochemiluminometric assay (ICMA). Results 1. The comparison for Ugn content during GnRHa stimulation testing between before and after therapy: Urinary stimulated LH content (ULH) before and after therapy were respectively ( 1.27 ± 1.63) IU and (0.07 ±0.06) IU;for urinary stimulated FSH content(l)FSH) were (6.38 ±3.85) II) and (0.54 ±0.30) IU. 2. Serum peak Gn and Ugn during GnRHa stimulation testing for monitoring therapy: When serum peak LH (PLH) and peak FSH (PFSH) were respectively no more than 2.30 IU · L-1 and 2.39 IU · L-1, the sensitivities to assess hypothalamic - pituitary - gonadal axis suppression were 95.45% and 100% , respectively, and both specificities were 100%. For the ULH and UFSH were respectively no more than 0.083 IU and 1.089 IU.the sensitivities were respectively 90.91% and 100% ,and both specificities were 100%. 3. The ratio of serum peak Gn to serum spontaneous Gn and the ratio of urinary stimulated Gn content to urinary spontaneous Gn content: When the ratio of PLH to serum spontaneous LH, the ratio of PFSH to serum spontaneous FSH, the ratio of ULH to urinary spontaneous LH content and the ratio of UFSH to urinary spontaneous FSH content were respectively no

  20. Serum gonadotropins after gonadotropin-releasing hormone injection in bulls subjected to spacial restriction.

    Gwazdauskas, F C; Bindas, E M; Anderson, G W; McGilliard, M L


    Response patterns of luteinizing hormone, follicle-stimulating hormone, and testosterone after injection of gonadotropin-releasing hormone were investigated in bulls grouped by weight (250 to 459 kg body weight) and confined five per pen in 9.2 or 6.4 m2 space per bull in two replicates. Blood samples were collected for 1 h prior to injection of 100 micrograms gonadotropin releasing hormone and 5 h after injection at 15-min intervals. Overall mean luteinizing hormone concentrations were not affected by spacial restriction or replicate. Interaction of treatment by time revealed that luteinizing hormone response curves were not similar. Restricted bulls had a higher response of luteinizing hormone to gonadotropin-releasing hormone. Follicle-stimulating hormone increased in all groups within 15 min and peaked at 219.4 ng/ml at 45 min. Both gonadotropin responses returned to preinjection concentrations by 4 h. Testosterone was affected by treatment, replicate, and time of sampling. Testosterone was higher in restricted bulls and higher in replicate 2. Mean testosterone peak following gonadotropin-releasing hormone was 3.86 ng/ml and occurred between 105 and 120 min which was approximately 90 min after the gonadotropin peaks. It appears that hormone responses to gonadotropin-releasing hormone were not depressed by spacial restriction, and additional spacial restriction of young bulls could be used commercially.

  1. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...


    ... drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Pfizer, Inc. The supplemental NADA extends the slaughter interval for intact male swine injected with..., filed a supplement to NADA 141-322 for IMPROVEST (gonadotropin releasing factor analog-diphtheria...

  2. Negative Feedback Governs Gonadotrope Frequency-Decoding of Gonadotropin Releasing Hormone Pulse-Frequency


    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...

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

    Musgrove Lois C


    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

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

    Turkstra, Jouwert Anne


    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 gametogen

  5. Molecular Mechanisms of Gonadotropin-Releasing Hormone Signaling: Integrating Cyclic Nucleotides into the Network

    Craig Alexander McArdle


    Full Text Available Gonadotropin-releasing hormone (GnRH is the primary regulator of mammalian reproductive function in both males and females. It acts via G-protein coupled receptors on gonadotropes to stimulate synthesis and secretion of the gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These receptors couple primarily via G-proteins of the Gq/11 family, driving activation of phospholipase C and mediating GnRH effects on gonadotropin synthesis and secretion. There is also good evidence that GnRH causes activation of other heterotrimeric G-proteins (Gs and Gi with consequent effects on cyclic AMP production, as well as for effects on the soluble and particulate guanylyl cyclases that generate cGMP. Here we provide an overview of these pathways. We emphasise mechanisms underpinning pulsatile hormone signaling and the possible interplay of GnRH and autocrine or paracrine regulatory mechanisms in control of cyclic nucleotide signaling.

  6. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates.

    Minakata, Hiroyuki


    Recent advances in peptide search methods have revealed two peptide systems that have been conserved through metazoan evolution. Members of the oxytocin/vasopressin-superfamily have been identified from protostomian and deuterostomian animals, indicating that the oxytocin/vasopressin hormonal system represents one of the most ancient systems. In most protostomian animals, a single member of the superfamily shares oxytocin-like and vasopressin-like actions. Co-occurrence of two members has been discovered in modern cephalopods, octopus, and cuttlefish. We propose that cephalopods have developed two peptides in the molluscan evolutionary lineage like vertebrates have established two lineages in the oxytocin/vasopressin superfamily. The existence of gonadotropin-releasing hormone (GnRH) in protostomian animals was initially suggested by immunohistochemical analysis using chordate GnRH antibodies. A peptide with structural features similar to those of chordate GnRHs was originally isolated from octopus, and an identical peptide has been characterized from squid and cuttlefish. Novel forms of GnRH-like molecules from other molluscs, an annelid, arthropods, and nematodes demonstrate somewhat conserved structures at the N-terminal regions; but structures of the C-terminal regions critical to gonadotropin-releasing activity are diverse. These findings may be important for the study of the molecular evolution of GnRH in protostomian animals.

  7. Treatment of canine pyometra with the gonadotropin-releasing hormone antagonist acyline: a case series.

    Batista, Pablo R; Blanco, Paula G; Gobello, Cristina


    To describe the effect of the third-generation gonadotropin-releasing hormone antagonist acyline in the treatment of 4 diestrous bitches with the cystic endometrial hyperplasia-pyometra complex. The 4 bitches were treated with 330 μg/kg of subcutaneous acyline on day 0 and antibiotics, and followed up for 2 weeks. One closed-cervix case showed cervical dilatation 36 hours after treatment, and all the 4 animals showed resolution of clinical signs starting on day 3 posttreatment. Ultrasonographic uterine diameters and luminal contents decreased in the bitches having high progesterone serum concentrations before treatment but not in those with low levels. Serum progesterone importantly decreased from high to basal concentrations in the 3 "ultrasonographically cured" animals. No local or systemic side effects related to the treatment were observed. The gonadotropin-releasing hormone antagonist acyline may have a promising place for the medical treatment of cystic endometrial hyperplasia-pyometra complex in dogs. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Efficacy and safety of gonadotropin-releasing hormone agonists used in the treatment of prostate cancer

    Choi S


    Full Text Available Seungtaek Choi, Andrew K LeeDepartment of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USAAbstract: Androgen deprivation therapy (ADT is the most effective systemic treatment for prostate cancer. ADT has been shown to have a high rate of response and to improve overall survival in patients with metastatic prostate cancer. In addition, multiple studies have shown that adding ADT to external beam radiation therapy leads to improvement in cure rates and overall survival in prostate cancer patients. The most commonly used ADT is gonadotropin-releasing hormone (GnRH agonist therapy. Although GnRH agonist therapy has significant benefits for patients with prostate cancer, it has also been shown to have significant side effects, including fatigue, hot flashes, decreased libido, decreased quality of life, obesity, diabetes mellitus, coronary artery disease, decreased bone mineral density, and increased risk of fractures. Therefore, it is crucial that the benefits of ADT be weighed against its potential adverse effects before its use.Keywords: androgen deprivation therapy, gonadotropin-releasing hormone agonists, prostate cancer

  9. Gonadotropin-releasing hormone: regulation of the GnRH gene.

    Lee, Vien H Y; Lee, Leo T O; Chow, Billy K C


    As the key regulator of reproduction, gonadotropin-releasing hormone (GnRH) is released by neurons in the hypothalamus, and transported via the hypothalamo-hypophyseal portal circulation to the anterior pituitary to trigger gonadotropin release for gonadal steroidogenesis and gametogenesis. To achieve appropriate reproductive function, mammals have precise regulatory mechanisms; one of these is the control of GnRH synthesis and release. In the past, the scarcity of GnRH neurons and their widespread distribution in the brain hindered the study of GnRH gene expression. Until recently, the development of GnRH-expressing cell lines with properties similar to those of in vivo GnRH neurons and also transgenic mice facilitated GnRH gene regulation research. This minireview provides a summary of the molecular mechanisms for the control of GnRH-I and GnRH-II gene expression. These include basal transcription regulation, which involves essential cis-acting elements in the GnRH-I and GnRH-II promoters and interacting transcription factors, and also feedback control by gonadotropins and gonadal sex steroids. Other physiological stimuli, e.g. insulin and melatonin, will also be discussed.

  10. Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis.

    Di Lauro, Luigi; Pizzuti, Laura; Barba, Maddalena; Sergi, Domenico; Sperduti, Isabella; Mottolese, Marcella; Amoreo, Carla Azzurra; Belli, Franca; Vici, Patrizia; Speirs, Valerie; Santini, Daniele; De Maria, Ruggero; Maugeri-Saccà, Marcello


    Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting. We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients). Overall response rate was 43.5% in patients treated with monotherapy and 51.3% with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2% versus 21.7%; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9% versus 43.5%; p = 0.05). In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting.

  11. Intraperitoneal administration of gonadotropin-releasing hormone-PE40 induces castration in male rats

    Li Yu; Zhong-Fang Zhang; Chun-Xia Jing; Feng-Lin Wu


    AIM: To evaluate the long-term effects of gonadotropin-releasing hormone (GnRH)-based vaccine on levels of GnRH antibody and testosterone, and vaccine-induced immunocastration on sexual behavior of male rats.METHODS: The rats were treated with GnRH-PE40 intraperitoneally every other day for 12 wk. GnRH antibody and testosterone level in rat blood were determined by ELISA and radioimmunoassay, respectively. Morphological changes in testes and sexual behavior of rats were evaluated.RESULTS: GnRH-PE40 induced a high production in GnRH antibody, decreased the serum testosterone level, testis atrophy and sexual function in rats.CONCLUSION: Intraperitoneal administration of GnRH-PE40 produces structural and functional castration of male rat reproductive system by inducing anti-GnRH antibody.

  12. P-fimbriae of Escherichia coli as carriers for gonadotropin releasing hormone: development of a recombinant contraceptive vaccine

    Zee, van der A.; Noordegraaf, C.V.; Bosch, van den H.; Gielen, J.; Bergmans, H.; Hoekstra, W.; Die, van I.


    The demand for an effective and low cost means of fertility control of domestic animals has raised interest in the development of contraceptive vaccines. A promising candidate for a vaccine component is the brain peptide gonadotropin releasing hormone (GnRH), which plays a central role in the regula

  13. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    Faraco, J.; Francke, U.; Toledo, S. [Stanford Univ. School of Medicine, CA (United States)


    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

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

    Schvartz, I.; Hazum, E.


    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.

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

    Cortés-Campos, Christian; Letelier, Joaquín; Ceriani, Ricardo; Whitlock, Kathleen E.


    ABSTRACT 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. PMID:26209533

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

    Christian Cortés-Campos


    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.

  17. Enzymatic tracer damage during the gonadotropin releasing hormone radioimmunoassay: analytical and immunological assessment

    O' Conner, J.L.; Lapp, C.A.; Clary, A.R.


    Hypothalamic supernatants from 60 day female rats were fractionated from Sephadex G-200 columns. The radioimmunoassay (RIA) for gonadotropin releasing hormone (GnRH) detected an apparently cross-reacting high molecular weight substance. The substance caused apparent displacement of iodinated GnRH binding in dose response fashion; however, no biological activity was observed in pituitary cell cultures. In order to determine whether the depressed binding might be caused by enzymatic degradation of iodinated GnRH during the RIA incubation, iodinated GnRH was preincubated under RIA conditions with either buffer or increasing concentrations of the GnRH cross-reacting material. Aliquots were subjected to polyacrylamide gel electrophoresis (PAGE) and the gels slices counted. Identical aliquots were subsequently used as iodinated hormone in the RIA of known quantities of synthetic GnRH. Tracer damage during the RIA-like preincubation period was reflected in the subsequent PAGE studies as decreased counts per minute in the intact GnRH peak and in the RIA studies as over-estimated quantification of the GnRH standards. This report describes such damage during the GnRH RIA and the data misinterpretations which result. 30 references, 6 figures, 1 table.

  18. Gonadotropin-releasing hormone is prerequisite for the constitutive expression of pituitary annexin A5.

    Yonezawa, Tomohiro; Watanabe, Aiko; Kurusu, Shiro; Kawaminami, Mitsumori


    Annexin A5 (ANXA5), a member of the structurally related family of annexin proteins, is expressed in pituitary gonadotropes. We previously reported that ANXA5 expression is stimulated by gonadotropin-releasing hormone (GnRH). In the present study, we investigated ANXA5 expression in the anterior pituitary gland of GnRH-deficient mutant hypogonadal (hpg) mice. RT-PCR demonstrated that luteinizing hormone β subunit (LHβ) and ANXA5 mRNA levels were both lower in the pituitary gland of hpg mice than in wild-type mice. Immunohistochemistry showed that ANXA5 expression throughout the pituitary gland was very low in hpg mice, suggesting that ANXA5 is diminished in gonadotropes and also in other cell types. Subcutaneous administration of a GnRH analogue, des-gly10 (Pro9)-GnRH ethylamide (1 μg/day for 7 days), augmented the expression of LHβ and ANXA5 in the pituitary gland in hpg mice. However, LHβ- and ANXA5-positive cells did not show exactly matched spatial distributions. These findings suggest that GnRH is necessary for constitutive ANXA5 expression in the pituitary gland, not only in gonadotropes but also in other pituitary gland cell types. A close relationship between ANXA5 and LHβ expression was confirmed. It is suggested that a significant role of ANXA5 in the physiologic secretion of LH.

  19. Ancient origins of metazoan gonadotropin-releasing hormone and their receptors revealed by phylogenomic analyses.

    Plachetzki, David C; Tsai, Pei-San; Kavanaugh, Scott I; Sower, Stacia A


    The discovery of genes related to gonadotropin-releasing hormones (GnRH) and their receptors from diverse species has driven important advances in comparative endocrinology. However, our view of the evolutionary histories and nomenclature of these gene families has become inconsistent as several different iterations of GnRH and receptor relationships have been proposed. Whole genome sequence data are now available for most of the major lineages of animals, and an exhaustive view of the phylogenies of GnRH and their receptors is now possible. In this paper, we leverage data from publically available whole genome sequences to present a new phylogenomic analysis of GnRH and GnRH receptors and the distant relatives of each across metazoan phylogeny. Our approach utilizes a phylogenomics pipeline that searches data from 36 whole genome sequences and conducts phylogenetic analyses of gene trees. We provide a comprehensive analysis of the major groupings of GnRH peptides, related hormones and their receptors and provide some suggestions for a new nomenclature. Our study provides a framework for understanding the functional diversification of this family of neuromodulatory peptides and their receptors.

  20. Conformation of an analog of human follicular gonadotropin releasing peptide TF14 in solution by 2D-NMR

    吴宏伟; 翟纯; 王德心; 林克椿


    Since the discovery of hF-GRP, several analogs have been synthesized in order to see their effects on the gonadotropin releasing activity, either as agonists or antagonists to this peptide. TF14 is one of these analogs, whose 14th position in the primary sequence is Phe instead of Asn in hF-GRP, while its activity is doubled. 2D-NMR (TOCSY, ROESY) was used to determine the conformation of TF14 in solution. Compared with hF-GRP, the whole peptide is in a non-typical more extended conformation, which may give some due to the relation between structure and function of these two peptides.

  1. Binding properties of solubilized gonadotropin-releasing hormone receptor: role of carboxylic groups

    Hazum, E.


    The interaction of /sup 125/I-buserelin, a superactive agonist of gonadotropin-releasing hormone (GnRH), with solubilized GnRH receptor was studied. The highest specific binding of /sup 125/I-buserelin to solubilized GnRH receptor is evident at 4/sup 0/C, and equilibrium is reached after 2 h of incubation. The soluble receptor retained 100% of the original binding activity when kept at 4 or 22/sup 0/C for 60 min. Mono- and divalent cations inhibited, in a concentration-dependent manner, the binding of /sup 125/I-buserelin to solubilized GnRH receptor. Monovalent cations require higher concentrations than divalent cations to inhibit the binding. Since the order of potency with the divalent cations was identical with that of their association constants to dicarboxylic compounds, it is suggested that there are at least two carboxylic groups of the receptor that participate in the binding of the hormone. The carboxyl groups of sialic acid residues are not absolutely required for GnRH binding since the binding of /sup 125/I-buserelin to solubilized GnRH receptor was only slightly affected by pretreatment with neuraminidase and wheat germ agglutinin. The finding that polylysines stimulate luteinizing hormone (LH) release from pituitary cell cultures with the same efficacy as GnRH suggest that simple charge interactions can induce LH release. According to these results, the authors propose that the driving force for the formation of the hormone-receptor complex is an ionic interaction between the positively charged amino acid arginine in position 8 and the carboxyl groups in the binding site.

  2. Antibodies against gonadotropin-releasing hormone in patients with posterior laryngitis.

    Pendleton, Hillevi; Alm, Ragnar; Nordin Fredrikson, Gunilla; Ohlsson, Bodil


    Patients with functional gastrointestinal disorders express antibodies against gonadotropin-releasing hormone (GnRH) in serum. One common cause of posterior laryngitis (PL) is extra-esophageal reflux, but a functional etiology has also been suggested. The aim of this study was to scrutinize patients with PL with regard to the presence of GnRH antibodies and to examine the association between antibodies and symptoms and reflux. Consecutive PL patients were included after examination. Serum was analyzed for the presence of antibodies using an enzyme-linked immunosorbent assay (ELISA) method and expressed as relative units (RU). Two age- and gender-matched healthy subjects per case served as controls. The prevalence of IgM GnRH antibodies in patients was 35% compared with 28% in controls (P = 0.06), with higher levels in patients (0.8 (0.3-2.2) RU) than in controls (0.2 (0.1-0.6) RU) (P = 0.007). The corresponding IgG antibody prevalences were 43% and 4%, respectively (P = 0.001), with no difference in levels (P = 0.70). There was no association between antibodies and clinical findings.

  3. Effect of gonadotropin-releasing hormone antagonist on primordial follicle survival in the primate ovary.

    Attaman, Jill; Arbogast, Laura K; Friedman, Chad I; Danforth, Douglas R


    To examine the effects of gonadotropin-releasing hormone (GnRH) antagonist on primordial follicle reserve in the primate ovary. A prospective basic research study in which 10 juvenile cynomolgus monkeys (Macaca fascicularis) had 1 ovary surgically removed. Six animals were then treated with the GnRH antagonist antide (1.0 mg/kg/day) for 14 days, and 4 animals were treated with vehicle. After treatment the contralateral ovary was removed and both ovaries were prepared for assessment of primordial, primary, and secondary follicle numbers. Antide treatment resulted in a modest (13%) but significant decrease in primordial follicle number in juvenile macaques (p = 0.048, n = 6). Three animals demonstrated a marked reduction in primordial follicles (19%, 25%, 36%) and 3 animals had no (primordial follicles after antide treatment. Control animals demonstrated no change in primordial follicle number following vehicle treatment. Antide had no effect on primary, secondary, or early antral follicle numbers and did not affect circulating estradiol concentrations. In contrast to mice, in which GnRH antagonist treatment markedly reduces primordial follicle reserve, the effect of antide in nonhuman primates was less dramatic and somewhat variable. These data suggest there may be a subset of animals susceptible to the adverse effects of GnRH antagonist on primordial follicle survival.

  4. Ovarian hyperstimulation syndrome prevention strategies: use of gonadotropin-releasing hormone antagonists.

    Griesinger, Georg


    The most serious complication of ovarian stimulation for in vitro fertilization is severe ovarian hyperstimulation syndrome (OHSS), a rare but potentially life-threatening condition. The present review discusses the place of gonadotropin-releasing hormone antagonists (GnRH-ant) in primary, secondary, and tertiary prevention of OHSS. Sound evidence indicates that the routine use of GnRH-ant instead of GnRH agonists (GnRHa) during ovarian stimulation drastically reduces the relative risk of OHSS. GnRH-ant are therefore useful for primary OHSS prevention, and an increased use of antagonists should help reduce the overall incidence of severe OHSS with its associated risks and complications. In patients on antagonist protocols identified to be at risk of developing severe OHSS, replacing human chorionic gonadotropin with GnRHa as a trigger of final oocyte maturation has been proposed as an effective measure of secondary prevention. A concept of combining GnRHa triggering with cryopreservation of all oocytes or embryos has yielded promising results as far as total avoidance of OHSS is concerned while providing a good chance of pregnancy for the patient in later frozen-thawed embryo transfers. In patients with early onset of OHSS, reinitiation of GnRH-ant in the luteal phase as a measure of tertiary prevention might lead to rapid regression of the syndrome; however only limited data on this new concept are available in the literature.

  5. Suppression of boar taint in cryptorchid pigs using a vaccine against the gonadotropin-releasing hormone.

    Gutzwiller, A; Ampuero Kragten, S


    Thirteen unilaterally cryptorchid Large White pigs, which had been immunized at 4 and 8 weeks of age and a third time at 64 ± 4 kg body weight against the gonadotropin releasing hormone with the vaccine Improvac®, were slaughtered at the age of 170 ± 9 days at a body weight of 102 ± 12 kg. Twelve pigs tested negative in the olfactory test of the salivary gland; their descended testicles were small and their fat androstenone concentration was low compared to normally developed boars of a previous experiment which had been vaccinated twice with Improvac® according the manufacturer's recommendation. One cryptorchid boar, which tested positive in the olfactory test and whose testicular weight and fat androstenone concentration corresponded to values of unvaccinated boars of the same age, obviously had not responded to the vaccination. It is an open question if the vaccination protocol for normal boars is sufficient to prevent boar taint in the majority of cryptorchid pigs, too.

  6. Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells

    Carina Lund


    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.

  7. Morphological changes of gonadotropin-releasing hormone neurons in the rat preoptic area across puberty

    Haogang Xue; Xiaodong Gai; Weiqi Sun; Chun Li; Quan Liu


    Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area may undergo mor-phological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green lfuorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive matu-ration. There was no signiifcant difference between male and female rats. Immunolfuorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.

  8. The use of gonadotropin-releasing hormone antagonist post-ovulation trigger in ovarian hyperstimulation syndrome.

    Chappell, Neil; Gibbons, William E


    The purpose of this paper is to assimilate all data pertaining to the use of gonadotropin-releasing hormone (GnRH) antagonists in in vitro fertilization cycles after ovulation trigger to reduce the symptoms of ovarian hyperstimulation syndrome (OHSS). A systematic review of the literature was performed to identify all studies performed on the use of a GnRH antagonist in IVF cycle post-ovulation trigger with patients at high risk for OHSS. Ten studies were identified and reviewed. Descriptions of the studies and their individual results are presented in the following manuscript. Due to significant heterogeneity among the studies, it was not possible to perform a group analysis. The use of GnRH antagonists post-ovulation trigger for treatment of OHSS has been considered for almost 20 years, though research into its use is sparse. Definitive conclusions and recommendations cannot be made at this time, though preliminary data from these trials demonstrate the potential for GnRH antagonists to play a role in the treatment of OHSS in certain patient populations.

  9. [Effect of bacterial endotoxin on migration of gonadotropin-releasing, hormone producing neurons in rat embryogenesis].

    Sharova, V S; Izvol'skaia, M S; Voronova, S N; Zakharova, L A


    The effect of bacterial lipopolysaccharide endotoxin (LPS), immune system activator, on differentiation and migration of gonadotropin-releasing, hormone producing neurons in rat embryogenesis has been studied. Intraperitoneal introduction of LPS (18 jg/kg) to pregnant rats on the 12th day of pregnancy led to 50% decrease in total number of GRH-neurons in the forebrain of 17-day-old embryos and 17% decrease in 19-day-old embryos. At the same time, the number of GRH-neurons in the nasal area of the head of 17- and 19-day-old embryos increased by 40 and 50%, respectively, whereas it increased by 20% in olfactory bulbs of 17-day-old embryos and did not changed in olfactory bulbs of 19-day-old embryos. Neither the total number of neurons nor their distribution patterns were affected by the introduction of LPS into pregnant rats on the 15th day of pregnancy. Singular localization of GRH-neurons in embryo forebrain was observed after LPS administration, whereas the neurons were located by groups of 3-4 cells in rostral areas. Therefore, at the early stages of pregnancy, LPS was shown to suppress initial stages of differentiation and migration of GRH producing neurons. The effects observed in our study may be mediated by LPS-induced, proinflammatory cytokines.

  10. Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.

    Rosati, Fabiana; Sturli, Niccolò; Cungi, Maria Chiara; Morello, Matteo; Villanelli, Fabio; Bartolucci, Gianluca; Finocchi, Claudia; Peri, Alessandro; Serio, Mario; Danza, Giovanna


    Neurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex. Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.0 nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50% after 90 min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90 min and by 3.5 times after 3 h, respectively. GnRH action is mediated by LH and 1.0 nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90 min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72 h. These data indicate for the first time that GnRH regulates both cholesterol and steroid biosynthesis in human neuronal-like cells and suggest a new physiological role for GnRH in the brain.

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

    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.

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

    Lim, Stefan; Pnueli, Lilach; Tan, Jing Hui; Naor, Zvi; Rajagopal, Gunaretnam; Melamed, Philippa


    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. Apoptotic death of prostate cancer cells by a gonadotropin-releasing hormone-II antagonist.

    Sumi Park

    Full Text Available Gonadotropin-releasing hormone-I (GnRH-I has attracted strong attention as a hormonal therapeutic tool, particularly for androgen-dependent prostate cancer patients. However, the androgen-independency of the cancer in advanced stages has spurred researchers to look for new medical treatments. In previous reports, we developed the GnRH-II antagonist Trp-1 to inhibit proliferation and stimulate the autophagic death of various prostate cancer cells, including androgen-independent cells. We further screened many GnRH-II antagonists to identify molecules with higher efficiency. Here, we investigated the effect of SN09-2 on the growth of PC3 prostate cancer cells. SN09-2 reduced the growth of prostate cancer cells but had no effect on cells derived from other tissues. Compared with Trp-1, SN09-2 conspicuously inhibited prostate cancer cell growth, even at low concentrations. SN09-2-induced PC3 cell growth inhibition was associated with decreased membrane potential in mitochondria where the antagonist was accumulated, and increased mitochondrial and cytosolic reactive oxygen species. SN09-2 induced lactate dehydrogenase release into the media and annexin V-staining on the PC3 cell surface, suggesting that the antagonist stimulated prostate cancer cell death by activating apoptotic signaling pathways. Furthermore, cytochrome c release from mitochondria to the cytosol and caspase-3 activation occurred in a concentration- and time-dependent manner. SN09-2 also inhibited the growth of PC3 cells xenotransplanted into nude mice. These results demonstrate that SN09-2 directly induces mitochondrial dysfunction and the consequent ROS generation, leading to not only growth inhibition but also apoptosis of prostate cancer cells.

  14. [Stimulation test of the adenohypophysis with arginine, gonadotropin-releasing hormone (GRH), and thyrotropin-releasing hormone (TRH) in 45, XO patients with Turner's syndrome (author's transl)].

    Rudolf, K; Kyank, H; Göretzlehner, G; Kunkel, S


    Pituitary stimulation tests with arginine, gonadotropin-releasing hormone (GRH) and thyrotropin-releasing hormone (TRH) were performed in five 45, XO patients with Turner's syndrome. Their ages ranged from 12--17 years. Serum levels of LH, FSH, PRL, HGH, and TSH were measured by RIA. The hypothalamo-pituitary system appeared normal in the patients with Turner's syndrome.

  15. Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

    Hertel, Niels; Stoltenberg, Meredin; Juul, A


    Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s...

  16. Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate

    Hertel, Niels; Stoltenberg, Meredin; Juul, A


    Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s...

  17. Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients

    ZHU Hong-lan; WANG Yan; LI Xiao-ping; WANG Chao-hua; WANG Yue; CUI Heng; WANG Jian-liu


    Background Recently,conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer.The preservation of these patients' future fertility has been the focus of recent interest.This study aimed to observe the effect of gonadotropin-releasing hormone agonists (GnRHa) cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients.Methods Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People's Hospital from January 2006 to July 2010 were retrospectively analyzed.This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy (n=5) without GnRHa or were historical controls (n=11).The disease recurrence,the menstruation status and reproductive outcome were followed up and compared between the two groups.Results There were no significant differences between both groups regarding age,body weight,height,marriage status,classification of the tumors,stage of the disease,as were the cumulative doses of each chemotherapeutic agent.One (1/16) patient in the study group while 2 (2/16) patients in the control group relapsed 2 years after conclusion of the primary treatment (P >0.05).All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment (P <0.05).There were 4 spontaneous pregnancies in the study group while 2 in the control group,all of the neonates were healthy.Conclusions GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate.Long-term follow up and large scale clinical studies are required.

  18. Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

    Ryo eNishiguchi


    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.

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

    Malpaux Benoît


    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.

  20. Gonadotropin releasing hormone in the primitive vertebrate family Myxinidae: reproductive neuroanatomy and evolutionary aspects.

    Sills, Eric Scott; Palermo, Gianpiero D


    The family Myxinidae embraces all hagfish species, and occupies an evolutionary niche intermediate between ancestral vertebrates and the gnathostomes (jawed vertebrates). Gonadotropin releasing hormone (GnRH) modulates neuroendocrine activity in vertebrates and works in the context of the hypothalamic-pituitary (H-P) axis. The appearance of this neuroendocrine axis marks one of the most crucial developmental achievements in vertebrate evolution, because it enabled further diversification in general growth, metabolism, osmoregulation and reproduction as jawed vertebrates evolved. GnRH studies in hagfish draw attention because such work may be considered as providing proxy data for similar investigations conducted upon long extinct species. Indeed, the fossil record reveals little anatomical difference between those hagfish living 300 million years ago and their modern descendants. Accordingly, the hagfish can offer important evolutionary lessons as they have some highly unusual characteristics not seen in any other vertebrate; they retain many representative features of an ancestral state from which all vertebrates originated. Indeed, because central control of reproduction is perhaps the most basic function of the vertebrate H-P axis, and given the importance of GnRH in this network, research on GnRH in hagfish can help elucidate the early evolution of the H-P system itself. Like all vertebrates, hagfish have a functional hypothalamic area and a pituitary gland, constituting a basic H-P axis. But what role does GnRH play in the reproductive system of this "living fossil"? How can understanding GnRH in hagfish help advance the knowledge of vertebrate neuroendocrinology? Here, information on neuroendocrine function and the role of GnRH specifically in this very basal vertebrate is reviewed.

  1. Gonadotropin-releasing hormone agonist use in men without a cancer registry diagnosis of prostate cancer

    Kuo Yong-fang


    Full Text Available Abstract Background Use of gonadotropin-releasing hormone (GnRH agonists has become popular for virtually all stages of prostate cancer. We hypothesized that some men receive these agents after only a limited work-up for their cancer. Such cases may be missed by tumor registries, leading to underestimates of the total extent of GnRH agonist use. Methods We used linked Surveillance, Epidemiology and End-Results (SEER-Medicare data from 1993 through 2001 to identify GnRH agonist use in men with either a diagnosis of prostate cancer registered in SEER, or with a diagnosis of prostate cancer based only on Medicare claims (from the 5% control sample of Medicare beneficiaries residing in SEER areas without a registered diagnosis of cancer. The proportion of incident GnRH agonist users without a registry diagnosis of prostate cancer was calculated. Factors associated with lack of a registry diagnosis were examined in multivariable analyses. Results Of incident GnRH agonist users, 8.9% had no diagnosis of prostate cancer registered in SEER. In a multivariable logistic regression model, lack of a registry diagnosis of prostate cancer in GnRH agonist users was significantly more likely with increasing comorbidity, whereas it was less likely in men who had undergone either inpatient admission or procedures such as radical prostatectomy, prostate biopsy, or transurethral resection of the prostate. Conclusion Reliance solely on tumor registry data may underestimate the rate of GnRH agonist use in men with prostate cancer.

  2. Functional Authentication of a Novel Gastropod Gonadotropin-Releasing Hormone Receptor Reveals Unusual Features and Evolutionary Insight

    Kavanaugh, Scott I.; Tsai, Pei-San


    A gonadotropin-releasing hormone (GnRH)-like molecule was previously identified in a gastropod, Aplysia californica, and named ap-GnRH. In this study, we cloned the full-length cDNA of a putative ap-GnRH receptor (ap-GnRHR) and functionally authenticated this receptor as a bona fide ap-GnRHR. This receptor contains two potential translation start sites, each accompanied by a Kozak sequence, suggesting the translation of a long and a short form of the receptor is possible. The putative ap-GnRH...

  3. Seasonal differences in the parameters of luteinizing hormone release to exogenous gonadotropin releasing hormone in prepubertal Holstein heifers in Sapporo.

    Kadokawa, Hiroya


    Stress due to summer heat has adverse effects on reproduction in Holstein dairy cattle. Summer suppression of reproduction of Holsteins can pose an important economic problem, even in Hokkaido prefecture located in the northern region of Japan. Hokkaido is one of the most important dairy farming areas of Japan. This study is an attempt to clarify the seasonal differences in the parameters of luteinizing hormone (LH) response to exogenous gonadotropin releasing hormone (GnRH) in Sapporo, Hokkaido, Japan. A total of 12 prepubertal heifers received an injection with GnRH analogue intramuscularly in either May (n=4, May group), July (n=4, July group), or November (n=4, November group), and serial blood samples were collected to analyze the parameters of the LH response curve after GnRH injection. The parameters were as follows: the basal LH concentration, peak LH concentration, duration from the time of GnRH injection to the time of the peak LH concentration, and area under the LH response curve (AUC). There were no significant differences in the basal and peak LH concentrations or the AUC among the three groups. The July group reached the LH peak significantly (P<0.05) faster than the May group, but there was no significant difference with the November group. Therefore, the results of the present study do not demonstrate an effect of summer heat on the LH response to the exogenous GnRH in Holstein heifers.

  4. The regulation and function of fibroblast growth factor 8 and its function during gonadotropin-releasing hormone neuron development

    Wilson CJ Chung


    Full Text Available Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF signaling regulates neuroendocrine progenitor cell proliferation, fate-specification, and cell survival, and therefore is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the gonadotropin-releasing hormone (GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus-pituitary-gonadal (HPG axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence, and hence HPG-function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid and epigenetic modifies control mouse OP Fgf8 transcription in the context of GnRH neuronal development, and mammalian reproductive success.

  5. 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

    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.


    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

  6. The gonadotropin-releasing hormone antagonist protocol--the protocol of choice for the polycystic ovary syndrome patient undergoing controlled ovarian stimulation

    Kol, Shahar; Homburg, Roy; Alsbjerg, Birgit


    Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-releasing...... hormone antagonist protocol should be the protocol of choice for the PCOS patient undergoing ovarian stimulation with gonadotropins for in vitro fertilization. If an excessive ovarian response is encountered, the clinician will always have two options: either to trigger final oocyte maturation...

  7. Effects of oral contraceptives or a gonadotropin-releasing hormone agonist on ovarian carcinogenesis in genetically engineered mice.

    Romero, Iris L; Gordon, Ilyssa O; Jagadeeswaran, Sujatha; Mui, Keeley L; Lee, Woo Seok; Dinulescu, Daniela M; Krausz, Thomas N; Kim, Helen H; Gilliam, Melissa L; Lengyel, Ernst


    Although epidemiologic evidence for the ability of combined oral contraception (OC) to reduce the risk of ovarian cancer (OvCa) is convincing, the biological mechanisms underlying this effect are largely unknown. We conducted the present study to determine if OC also influences ovarian carcinogenesis in a genetic mouse model and, if so, to investigate the mechanism underlying the protective effect. LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with ethinyl estradiol plus norethindrone, contraceptive hormones commonly used in combined OC, or norethindrone alone, or a gonadotropin-releasing hormone agonist. The combined OC had a 29% reduction in mean total tumor weight compared with placebo (epithelial tumor weight, -80%). Norethindrone alone reduced mean total tumor weight by 42% (epithelial tumor weight, -46%), and the gonadotropin-releasing hormone agonist increased mean total tumor weight by 71% (epithelial tumor weight, +150%). Large variations in tumor size affected the P values for these changes, which were not statistically significant. Nonetheless, the OC reductions are consistent with the epidemiologic data indicating a protective effect of OC. Matrix metalloproteinase-2 activity was decreased in association with OC, indicating that OC may affect ovarian carcinogenesis by decreasing proteolytic activity, an important early event in the pathogenesis of OvCa. In contrast, OC increased invasion in a K-ras/Pten OvCa cell line established from the mouse tumors, suggesting that OC hormones, particularly estrogen, may have a detrimental effect after the disease process is under way. Our study results support further investigation of OC effects and mechanisms for OvCa prevention.

  8. 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

    D.C.M. van der Kaay (Danielle); F.H. de Jong (Frank); S.R. Rose (Susan); R.J.H. Odink (Roelof); W.M. Bakker-Van Waarde (Willie); E.J. Sulkers (Eric); A.C.S. Hokken-Koelega (Anita)


    textabstractAims: 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 gro

  9. Luteinizing Hormone Secretion during Gonadotropin-Releasing Hormone Stimulation Tests in Obese Girls with Central Precocious Puberty

    Lee, Hae Sang; Yoon, Jong Seo; Hwang, Jin Soon


    Objective: Girls with precocious puberty have high luteinizing hormone (LH) levels and advanced bone age. Obese children enter puberty at earlier ages than do non-obese children. We analyzed the effects of obesity on LH secretion during gonadotropin-releasing hormone (GnRH) tests in girls with precocious puberty. Methods: A total of 981 subjects with idiopathic precocious puberty who had undergone a GnRH stimulation testing between 2008 and 2014 were included in the study. Subjects were divided into three groups based on body mass index (BMI). Auxological data and gonadotropin levels after the GnRH stimulation test were compared. Results: In Tanner stage 2 girls, peak stimulated LH levels on GnRH test were 11.9±7.5, 10.4±6.4, and 9.1±6.1 IU/L among normal-weight, overweight, and obese subjects, respectively (p=0.035 for all comparisons). In Tanner stage 3 girls, peak stimulated LH levels were 14.9±10.9, 12.8±7.9, and 9.6±6.0 IU/L, respectively (p=0.022 for all comparisons). However, in Tanner stage 4 girls, peak stimulated LH levels were not significantly different among normal, overweight, and obese children. On multivariate analysis, BMI standard deviation score was significantly and negatively associated with peak LH (β=-1.178, p=0.001). Conclusion: In girls with central precocious puberty, increased BMI was associated with slightly lower peak stimulated LH levels at early pubertal stages (Tanner stages 2 and 3). This association was not valid in Tanner stage 4 girls. PMID:27215137

  10. Identification and distribution of gonadotropin-releasing hormone-like peptides in the brain of horseshoe crab Tachypleus tridentatus

    HUANG Huiyang; LI Linming; YE Haihui; FENG Biyun; LI Shaojing


    Gonadotropin-releasing hormone (GnRH) is a crucial peptide for the regulation of reproduction.Using immunological techniques,we investigated the presence of GnRH in horseshoe crab Tachypleus tridentatus.Octopus GnRH-like immunoreactivity,tunicate GnRH-like immunoreactivity,and lamprey GnRH-I-like immunoreactivity were detected in the neurons and fibers of the protocerebrum.However,no mammal GnRH-like immunoreactivity or lamprey GnRH-Ⅲ-like immunoreactivity was observed.Our results suggest that a GnRH-like factor,an ancient peptide,existed in the brain of T.tridentatus and may be involved in the reproductive endocrine system.

  11. The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS

    Eftekhar, Maryam; Miraj, Sepideh; Mortazavifar, Zahrasadat


    Background: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. Objective: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. Materials and Methods: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. Results: The pregnancy outcomes were not significantly different between two groups (p=0.224). Conclusion: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes. PMID:27679825

  12. Pregnancy rates to timed artificial insemination in dairy cows treated with gonadotropin-releasing hormone or porcine luteinizing hormone.

    Colazo, M G; Gordon, M B; Rajamahendran, R; Mapletoft, R J; Ambrose, D J


    We compared the effects of porcine luteinizing hormone (pLH) versus gonadotropin-releasing hormone (GnRH) on ovulatory response and pregnancy rate after timed artificial insemination (TAI) in 605 lactating dairy cows. Cows (mean+/-SEM: 2.4+/-0.08 lactations, 109.0+/-2.5 d in milk, and 2.8+/-0.02 body condition score) at three locations were assigned to receive, in a 2x2 factorial design, either 100 microg GnRH or 25mg pLH im on Day 0, 500 microg cloprostenol (PGF) on Day 7, and GnRH or pLH on Day 9, with TAI 14 to 18h later. Ultrasonographic examinations were performed in a subset of cows on Days 0, 7, 10, and 11 to determine ovulations, presence of corpus luteum, and follicle diameter and in all cows 32 d after TAI for pregnancy determination. In 35 cows, plasma progesterone concentrations were determined 0, 3, 4, 5, 6, 7, and 12 d after ovulation. The proportion of noncyclic cows and cows with ovarian cysts on Day 0 were 12% and 6%, respectively. Ovulatory response to first treatment was 62% versus 44% for pLH and GnRH and 78% versus 50% for noncyclic and cyclic cows (PpLH or GnRH, cyclic status, presence of an ovarian cyst, and preovulatory follicle size did not affect pregnancy rate. Plasma progesterone concentrations after TAI did not differ among treatments. Pregnancy rate to TAI was greater (PpLH group (42%) than in the other three groups (28%, 30%, and 26% for GnRH/PGF/GnRH, pLH/PGF/GnRH, and pLH/PGF/pLH, respectively). Although only 3% of cows given pLH in lieu of GnRH on Day 9 lost their embryo versus 7% in those subjected to a conventional TAI using two GnRH treatments, the difference was not statistically significant. In summary, pLH treatment on Day 0 increased ovulatory response but not pregnancy rate. Cows treated with GnRH/PGF/pLH had the highest pregnancy rate to TAI, but progesterone concentrations after TAI were not increased. In addition, preovulatory follicle diameter did not affect pregnancy rate.

  13. Factors to predict positive results of gonadotropin releasing hormone stimulation test in girls with suspected precocious puberty.

    Nam, Hyo-Kyoung; Rhie, Young Jun; Son, Chang Sung; Park, Sang Hee; Lee, Kee-Hyoung


    Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.

  14. Effects of a gonadotropin-releasing hormone vaccine on ovarian cyclicity and uterine morphology of an Asian elephant (Elephas maximus).

    Boedeker, Nancy C; Hayek, Lee-Ann C; Murray, Suzan; de Avila, David M; Brown, Janine L


    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.

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

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


    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.

  16. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

    Erik eHrabovszky


    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  17. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series

    Zagouri, F; Sergentanis, T N; Koutoulidis, V; Sparber, C; Steger, G G; Dubsky, P; Zografos, G C; Psaltopoulou, T; Gnant, M; Dimopoulos, M-A; Bartsch, R


    Background: Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce. Methods: In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated. Results: Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted. Conclusion: Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients. PMID:23722469

  18. Treatment of cryptorchidism with human chorionic gonadotropin or gonadotropin releasing hormone. A double-blind controlled study of 243 boys

    Christiansen, P; Müller, J; Buhl, S;


    We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled...... the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p......% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies...

  19. The role of Serine Proteases and Serine Protease Inhibitors in the migration of Gonadotropin-Releasing Hormone neurons

    Silverman Ann-Judith


    Full Text Available Abstract Background Mechanisms regulating neuronal migration during development remain largely undefined. Extracellular matrix cues, target site released factors, and components of the migratory neurons themselves are likely all coordinated in time and space directing neurons to their appropriate locations. We have studied the effects of proteases and their inhibitors on the extracellular matrix and the consequences to the migration of gonadotropin releasing hormone (GnRH neurons in the embryonic chick. Chick GnRH neurons differentiate in the olfactory epithelium, migrate along the olfactory nerve and enter the forebrain. The accessibility of this coherent cell group make it amenable for studying protease/inhibitor roles in migratory processes. Results Affigel blue beads were used to deliver a serine protease inhibitor, protease nexin-1 (PN-1, and a target protease, trypsin, to the olfactory epithelium coincident with initiation of GnRH neuronal migration. PN-1 inhibited neuronal migration while trypsin accelerated their transit into the CNS. Prior to initiation of migration, neither PN-1 nor trypsin altered the timing of neuronal exit. Trypsin did, however, accelerate the timing of neuronal crossing into the nerve-forebrain junction. Conclusions These data support the hypothesis that protease activity modulates neuronal movements across barriers. Moreover, the data suggest, for the first time, that aspects of GnRH neuronal migration may be cell autonomous but modulated by ECM alterations.

  20. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome.

    Bosch, Ernesto; Valencia, Iván; Escudero, Ernesto; Crespo, Juana; Simón, Carlos; Remohí, José; Pellicer, Antonio


    To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. Prospective observational study. In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. Cycles were grouped according to serum P level on the day of hCG administration ( or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.

  1. Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons

    Perrine Barraud


    Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs. Here, we demonstrate that in homozygous Sox10lacZ/lacZ mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting. Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.

  2. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH in cystic fibrosis epithelial cells.

    Nathalie Benz

    Full Text Available Cystic fibrosis (CF, the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(- channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5 directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(- channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R and that GnRH induces an AnxA5 overexpression and an increased Cl(- channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  3. Body image and depression in girls with idiopathic precocious puberty treated with gonadotropin-releasing hormone analogue

    Choi, Min-Seon


    Purpose Precocious puberty (PP) is associated with psychological and behavioral problems. This study aimed to evaluate the perception of body image and depression in girls with PP receiving gonadotropin-releasing hormone (GnRH) analogue therapy. Methods From March to August 2013, 82 girls with PP receiving GnRH analogue therapy were enrolled. Height, weight, body mass index, and stages of pubertal development were assessed. Participants completed a series of questionnaires on their body image perception and pubertal self-assessment. The depression score was calculated using the Korean Kovacs' Children's Depression Inventory. Results The patients perceived their body to be more obese than the controls did. The mean depression score did not differ between the patients and controls. The mean depression scores according to Tanner stages (1: prepubertal, 2: early pubertal, and 3–5: mid to late pubertal stage) by self-assessment were 5.2±3.6, 6.8±4.9, and 11.4±10.1 (Pperception of overall body build and figure (%) and the mean depression scores in patients were: dissatisfied (25.6%, 9.7±7.8) and satisfied (74.4%, 5.5±3.4) (Pperception of pubertal status and satisfaction about height or weight are unrelated to objective physical findings. Patients with PP are prone to distorted perception about their body image and breast development. Such incorrect body image seems to contribute to depression score. PMID:27777908

  4. Changes in gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor gene expression after an increase in carbon monoxide concentration in the cavernous sinus of male wild boar and pig crossbread.

    Romerowicz-Misielak, M; Tabecka-Lonczynska, A; Koziol, K; Gilun, P; Stefanczyk-Krzymowska, S; Och, W; Koziorowski, M


    Previous studies indicate that there are at least a few regulatory systems involved in photoperiodic synchronisation of reproductive activity, which starts with the retina and ends at the gonadotropin-releasing hormone (GnRH) pulse generator. Recently we have shown indicated that the amount of carbon monoxide (CO) released from the eye into the ophthalmic venous blood depends on the intensity of sunlight. The aim of this study was to test whether changes in the concentration of carbon monoxide in the ophthalmic venous blood may modulate reproductive activity, as measured by changes in GnRH and GnRH receptor gene expression. The animal model used was mature male swine crossbred from wild boars and domestic sows (n = 48). We conducted in vivo experiments to determine the effect of increased CO concentrations in the cavernous sinus of the mammalian perihypophyseal vascular complex on gene expression of GnRH and GnRH receptors as well as serum luteinizing hormone (LH) levels. The experiments were performed during long photoperiod days near the summer solstice (second half of June) and short photoperiod days near the winter solstice (second half of December). These crossbred swine demonstrated a seasonally-dependent marked variation in GnRH and GnRH receptor gene expression and systemic LH levels in response to changes in CO concentration in ophthalmic venous blood. These results seem to confirm the hypothesis of humoral phototransduction as a mechanism for some of bright light's effects in animal chronobiology and the effect of CO on GnRH and GnRH receptor gene expression.

  5. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Qi-Hong Sun; Yu Zheng; Xiao-Lin Zhang; Yi-Ming Mu


    Background:Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH).Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty.The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.Methods:A study of 91 IHH,27 CDP patients,6 prepubertal children,and 20 pubertal adults was undertaken.Blood samples were obtained at 0,30,60,and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured.For each parameter,the sensitivities and specificities were estimated,and the receiver operating characteristic (ROC) curves were constructed.Results:The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males.Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.Conclusions:Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males,but unnecessary in females.The most useful predictor is serum basal or peak LH to differentiate these two disorders in males,but serum basal LH or FSH in females.

  6. Postoperative Levonorgestrel-Releasing Intrauterine System Insertion After Gonadotropin-Releasing Hormone Agonist Treatment for Preventing Endometriotic Cyst Recurrence: A Prospective Observational Study.

    Kim, Min Kyoung; Chon, Seung Joo; Lee, Jae Hoon; Yun, Bo Hyon; Cho, SiHyun; Choi, Young Sik; Lee, Byung Seok; Seo, Seok Kyo


    The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence. The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis. Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosis were 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P < .0001 and 0.50 vs 4.26 U/mL, P < .0001, respectively). Of the 28 patients, 13 (46.4%) simultaneously had adenomyosis, and 2 (7.1%) underwent LNG-IUS removal because of unresolved vaginal bleeding and dysmenorrhea. Recurrence was noted in 2 (7.1%) women. Postoperative LNG-IUS insertion after GnRH-a treatment is an effective approach for preventing endometriotic cyst recurrence, especially in women who do not desire to conceive.

  7. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)


    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  8. Impact of gonadotropin-releasing hormone antagonist addition on pregnancy rates in gonadotropin-stimulated intrauterine insemination cycles

    Shikha Jain


    Full Text Available OBJECTIVES: The objective of the study is to evaluate the efficacy of gonadotropin-releasing hormone (GnRH antagonist in improving clinical pregnancy rate in gonadotropin-stimulated intrauterine insemination (IUI cycles in patients of unexplained infertility. STUDY DESIGN: This was a prospective, randomized case-controlled study. SETTINGS: The study was conducted in the infertility clinic of a tertiary care center. MATERIALS AND METHODS: Four hundred twenty-seven women undergoing IUI following controlled ovarian stimulation with gonadotropins (recombinant follicle-stimulating hormone [r-FSH] 75 IU/day were randomly divided into two groups. Women in Group I received GnRH antagonist (Cetrorelix 0.25 mg/day in a multiple dose flexible protocol. Women in Group II received r-FSH alone. Ovulatory trigger was given with human chorionic gonadotropin 5000 IU when dominant follicle was ≥18 mm. IUI was performed within 44-48 h. Both groups received similar luteal phase support. Primary outcome measure was clinical pregnancy rate. The trial was powered to detect an absolute increase in clinical pregnancy rate by 13% from an assumed 20% clinical pregnancy rate in the control group, with an alpha error level of 0.05 and a beta error level of 0.20. RESULTS: Clinical pregnancy rate in Groups I and II was 27.6% (n = 56 and 26.5% (n = 54, respectively (P=0.800. Ongoing pregnancy and multiple pregnancy rates were likewise similar between the groups. CONCLUSIONS: Addition of GnRH antagonist to gonadotropin-stimulated IUI cycles results in no significant difference in clinical pregnancy rate.

  9. Predictive Value of Dental Maturity for a Positive Gonadotropin-Releasing Hormone Stimulation Test Result in Girls with Precocious Puberty


    Dental maturity is associated with skeletal maturity, which is advanced in girls with central precocious puberty (CPP). We investigated the performance of dental maturity as a screening method for CPP using mandibular second premolar and molar calcification stages, assessed the associated anthropometric and laboratory factors, and evaluated pubertal response predictors using the gonadotropin-releasing hormone stimulation test (GnRHST) in prepubertal and pubertal girls. A prospective case-control study was conducted in girls, aged 7.0–8.9 years, classified into pubertal (peak luteinizing hormone [LH] after GnRHST ≥ 5 IU/L), prepubertal (peak LH < 5 IU/L), and control groups. Auxological and biochemical tests, panoramic radiographs, and GnRHSTs in participants with breast development were conducted. Dental maturity was assessed using the Demirjian index (DI). We included 103 girls (pubertal, 40; prepubertal, 19; control, 44). Chronological age (CA) was not significantly different between groups. Bone age (BA) and BA advancement was higher in the pubertal and prepubertal groups. Increased DI values at the mandibular second premolar and molar were significantly associated with CA, BA, BA advancement, height standard deviation score (SDS), peak LH after GnRHST, and insulin-like growth factor-I (IGF-I) (all P < 0.05). Moreover, odds ratio (OR) of the mandibular second premolar and molar (a DI value of ≥ E) for predicting a positive response to GnRHST was 8.7 (95% confidence intervals [CI], 2.9–26.1) and 5.2 (95% CI, 2.2–12.7), respectively. Dental maturity was a strong predictor for diagnosing CPP. Determining dental maturity in girls with suspected precocious puberty might help determine the performance of GnRHSTs. PMID:28049241

  10. Effects of a gonadotropin-releasing hormone antagonist on gonadotropin levels in Masu salmon and Sockeye salmon.

    Amano, Masafumi; Ikuta, Kazumasa; Kitamura, Shoji


    The salmon gonadotropin-releasing hormone (sGnRH) is considered to be involved in gonadal maturation via gonadotropin (GTH) secretion in salmonid fishes. However, there is no direct evidence for endogenous sGnRH-stimulated GTH secretion in salmonids. In this study, to clarify whether endogenous sGnRH stimulates GTH secretion, we examined the effects of the mammalian GnRH (mGnRH) antagonist [Ac-Delta(3)-Pro(1), 4FD-Phe(2), D-Trp(3,6)]-mGnRH on luteinizing hormone (LH) levels in 0-year-old masu salmon Oncorhynchus masou and sockeye salmon Oncorhynchus nerka. First, the effects of the GnRH antagonist on LH release were examined in 0-year-old precocious male masu salmon. GnRH antagonist treatment for 3 hr significantly inhibited an increase in plasma LH levels that was artificially induced by exogenous sGnRH administration, indicating that the GnRH antagonist is effective in inhibiting LH release from the pituitary. Subsequently, we examined the effect of the GnRH antagonist on LH synthesis in 0-year-old immature sockeye salmon that were pretreated with exogenous testosterone for 42 days to increase the pituitary LH contents; the testosterone treatment did not affect the plasma LH levels. GnRH antagonist treatment slightly but significantly inhibited an increase in the testosterone-stimulated pituitary LH content levels. However, no significant differences in the plasma LH levels were observed between the GnRH antagonist-treated and control groups. These results suggest that endogenous sGnRH is involved in LH secretion in salmonid fishes.

  11. In vitro fertility rate of 129 strain is improved by buserelin (gonadotropin-releasing hormone) administration prior to superovulation.

    Vasudevan, K; Sztein, J M


    The 129 mice are well recognized for their low fertility and it is speculated that this lack of fertility may be due to the oocyte condition. In this study we investigated superovulation regimens for the 129S1/SvImJ mouse strain to improve the oocyte quality and fertility rate of in vitro fertilization (IVF). Female mice were divided into four groups based on hormone and timing of injection. Group 1 received pregnant mare serum gonadotropin (PMSG) and 48 h later human chorionic gonadotropin (hCG); using the same dose, group 2 received hCG 52 h post-PMSG and group 3, 55 h post-PMSG. Group 4 received buserelin (gonadotropin-releasing hormone agonist [GnRH]) followed 24 h later by PMSG and then hCG 55 h post-PMSG. IVF was performed using 129S1/SvImJ oocytes and sperm; C57BL/6J sperm with 129S1/SvImJ oocytes was used as fertility control. The IVF fertility rate was 1% (Groups 1 and 2), 17% (Group 3) and 55% (Group 4) for 129 oocytes fertilized with 129 sperm. For 129 oocytes fertilized with C57BL/6J sperm, the fertility rate was 5% (Group 1), 10% (Group 2), 40% (Group 3) and 59% (Group 4). These results suggest that extending the interval time between PMSG and hCG and giving GnRH in addition to the standard PMSG and hCG treatments can improve IVF fertility rate of 129S1/SvImJ mouse strains significantly.

  12. Seasonal variation in the gonadotropin-releasing hormone response to kisspeptin in sheep: possible kisspeptin regulation of the kisspeptin receptor.

    Li, Qun; Roa, Alexandra; Clarke, Iain J; Smith, Jeremy T


    Kisspeptin signaling in the hypothalamus appears critical for the onset of puberty and driving the reproductive axis. In sheep, reproduction is seasonal, being activated by short days and inhibited by long days. During the non-breeding (anestrous) season, gonadotropin-releasing hormone (GnRH) and gonadotropin secretion is reduced, as is the expression of Kiss1 mRNA in the brain. Conversely, the luteinizing hormone response to kisspeptin during this time is greater. To determine whether the GnRH response to kisspeptin is increased during anestrus, we utilized hypophysial portal blood sampling. In anestrus ewes, the GnRH and LH responses to kisspeptin were greater compared to the breeding season (luteal phase). To ascertain whether this difference reflects a change in Kiss1r, we measured its expression on GnRH neurons using in situ hybridization. The level of Kiss1r was greater during the non-breeding season compared to the breeding season. To further examine the mechanism underlying this change in Kiss1r, we examined Kiss1r/GnRH expression in ovariectomized ewes (controlling for sex steroids) during the breeding and non-breeding seasons, and also ovariectomized non-breeding season ewes with or without estradiol replacement. In both experiments, Kiss1r expression on GnRH neurons was unchanged. Finally, we examined the effect of kisspeptin treatment on Kiss1r. Kiss1r expression on GnRH neurons was reduced by kisspeptin infusion. These studies indicate the kisspeptin response is indeed greater during the non-breeding season and this may be due in part to increased Kiss1r expression on GnRH neurons. We also show that kisspeptin may regulate the expression of its own receptor.

  13. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.


    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  14. Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (Carassius auratus)

    Illing, Nicola; Troskie, Brigitte E.; Nahorniak, Carol S.; Janet P Hapgood; Peter, Richard E.; Millar, Robert P.


    In the goldfish (Carassius auratus) the two endogenous forms of gonadotropin-releasing hormone (GnRH), namely chicken GnRH II ([His5,Trp7,Tyr8]GnRH) and salmon GnRH ([Trp7,Leu8]GnRH), stimulate the release of both gonadotropins and growth hormone from the pituitary. This control is thought to occur by means of the stimulation of distinct GnRH receptors. These receptors can be distinguished on the basis of differential gonadotropin and growth hormone releasing activities of naturally occurring...

  15. Maternal behavior in transgenic mice with reduced fibroblast growth factor receptor function in gonadotropin-releasing hormone neurons

    Brooks Leah R


    Full Text Available Abstract Background Fibroblast growth factors (FGFs and their receptors (FGFRs are necessary for the proper development of gonadotropin-releasing hormone (GnRH neurons, which are key activators of the hypothalamo-pituitary-gonadal axis. Transgenic mice that have the targeted expression of a dominant negative FGFR (dnFGFR in GnRH neurons (dnFGFR mice have a 30% decrease of GnRH neurons. Additionally, only 30–40% of the pups born to the transgenic dams survive to weaning age. These data raised the possibility that FGFR defects in GnRH neurons could adversely affect maternal behavior via novel mechanisms. Methods We first determined if defective maternal behavior in dnFGFR mothers may contribute to poor pup survival by measuring pup retrieval and a battery of maternal behaviors in primiparous control (n = 10–12 and dnFGFR (n = 13–14 mothers. Other endocrine correlates of maternal behaviors, including plasma estradiol levels and hypothalamic pro-oxyphysin and GnRH transcript levels were also determined using enzyme-linked immunoassay and quantitative reverse transcription polymerase chain reaction, respectively. Results Maternal behaviors (% time crouching with pups, time off pups but not feeding, time feeding, and total number of nesting bouts were not significantly different in dnFGFR mice. However, dnFGFR dams were more likely to leave their pups scattered and took significantly longer to retrieve each pup compared to control dams. Further, dnFGFR mothers had significantly lower GnRH transcripts and circulating E2, but normal pro-oxyphysin transcript levels. Conclusions Overall, this study suggests a complex scenario in which a GnRH system compromised by reduced FGF signaling leads to not only suboptimal reproductive physiology, but also suboptimal maternal behavior.

  16. Gonadotropin-releasing hormone positively regulates steroidogenesis via extracellular signal-regulated kinase in rat Leydig cells

    Bing Yao; Hai-Yan Liu; Yu-Chun Gu; Shan-Shan Shi; Xiao-Qian Tao; Xiao-Jun Li; Yi-Feng Ge; Ying-Xia Cui; Guo-Bin Yang


    Gonadotropin-releasing hormone (GnRH) is secreted from neurons within the hypothalamus and is necessary for reproductive function in all vertebrates. GnRH is also found in organs outside of the brain and plays an important role in Leydig cell steroidogenesis in the testis. However, the signalling pathways mediating this function remain largely unknown. In this study, we investigated whether components of the mitogen-activated protein kinase (MAPK) pathways are involved in GnRH agonist (GnRHa)-induced testis steroidogenesis in rat Leydig cells. Primary cultures of rat Leydig cells were established. The expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and the production of testosterone in response to GnRHa were examined at different doses and for different durations by RT-PCR, Western blot analysis and radioimmunoassay (RIA). The effects of GnRHa on ERK1/2, JNK and p38 kinase activation were also investigated in the presence or absence of the MAPK inhibitor PD-98059 by Western blot analysis. GnRHa induced testosterone production and upregulated 3β-HSD expression at both the mRNA and protein levels; it also activated ERK1/2, but not JNK and p38 kinase. Although the maximum effects of GnRHa were observed at a concentration of 100 nmnol L-1 after 24 h, activation of ERK1/2 by GnRHa reached peak at 5 min and it returned to the basal level within 60 min. PD-98059 completely blocked the activation of ERK1/2, the upregulation of 3β-HSD and testosterone production. Our data show that GnRH positively regulates steroidogenesis via ERK signalling in rat Leydig cells. ERK1/2 activation by GnRH may be responsible for the induction of 3β-HSDgene expression and enzyme production, which may ultimately modulate steroidogenesis in rat Leydig cells.

  17. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Wei Ling Lim


    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  18. Histone deacetylases regulate gonadotropin-releasing hormone I gene expression via modulating Otx2-driven transcriptional activity.

    Lu Gan

    Full Text Available BACKGROUND: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of HDACs activities by trichostatin A (TSA and valproic acid (VPA promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1-7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modulated by Grg4, a member of the Groucho-related-gene (Grg family. In the present study, the expression of Otx2 was downregulated by TSA and VPA in GT1-7 cells, accompanied with the opposite changes of Grg4 expression. Chromatin immunoprecipitation and electrophoretic mobility shift assays demonstrated that the DNA-binding activity of Otx2 to Gnrh1 gene was suppressed by TSA and VPA. Overexpression of Otx2 partly abolished the TSA- and VPA-induced downregulation of Gnrh1 gene expression. CONCLUSIONS/SIGNIFICANCE: Our data indicate that HDAC inhibitors downregulate Gnrh1 gene expression via repressing Otx2-driven transcriptional activity. This study should provide an insight for our understanding on the effects of HDACs in the reproductive system and suggests that HDACs could be potential novel targets for the therapy of GnRH-related diseases.

  19. Addition of gonadotropin releasing hormone agonist for luteal phase support in in-vitro fertilization: an analysis of 2739 cycles

    Şimşek, Erhan; Kılıçdağ, Esra Bulgan; Aytaç, Pınar Çağlar; Çoban, Gonca; Şimşek, Seda Yüksel; Çok, Tayfun; Haydardedeoğlu, Bülent


    Objective Luteal phase is defective in in vitro fertilization (IVF) cycles, and many regimens were tried for the very best luteal phase support (LPS). Gonadotropin releasing hormone (GnRH) agonist use, which was administered as an adjunct to the luteal phase support in IVF cycles, was suggested to improve pregnancy outcome measures in certain randomized studies. We analyzed the effects of addition of GnRH agonist to standard progesterone luteal support on pregnancy outcome measures, particularly the live birth rates. Material and Methods This is a retrospective cohort study, including 2739 IVF cycles. Long GnRH agonist and antagonist stimulation IVF cycles with cleavage-stage embryo transfer were included. Cycles were divided into two groups: Group A included cycles with single-dose GnRH agonist plus progesterone LPS and Group B included progesterone only LPS. Live birth rates were the primary outcome measures of the analysis. Miscarriage rates and multiple pregnancy rates were the secondary outcome measures. Results Live birth rates were not statistically different in GnRH agonist plus progesterone (Group A) and progesterone only (Group B) groups in both the long agonist and antagonist stimulation arms (40.8%/41.2% and 32.8%/34.4%, p<0.05 respectively). Moreover, pregnancy rates, implantation rates, and miscarriage rates were found to be similar between groups. Multiple pregnancy rates in antagonist cycles were significantly higher in Group A than those in Group B (12.0% and 6.9%, respectively). Conclusion A beneficial effect of a single dose of GnRH agonist administration as a luteal phase supporting agent is yet to be determined because of the wide heterogeneity of data present in literature. Well-designed randomized clinical studies are required to clarify any effect of luteal GnRH agonist addition on pregnancy outcome measures with different doses, timing, and administration routes of GnRH agonists. PMID:26097392

  20. Brain morphology and immunohistochemical localization of the gonadotropin-releasing hormone in the bluefin tuna, Thunnus thynnus

    G Palmieri


    Full Text Available The present study was focused on the morphology of the diencephalic nuclei (likely involved in reproductive functions as well as on the distribution of GnRH (gonadotropin-releasing hormone in the rhinencephalon, telencephalon and the diencephalon of the brain of bluefin tuna (Thunnus thynnus by means of immunohistochemistry. Bluefin tuna has an encephalization quotient (QE similar to that of other large pelagic fish. Its brain exhibits well-developed optic tecta and corpus cerebelli. The diencephalic neuron cell bodies involved in reproductive functions are grouped in two main nuclei: the nucleus preopticus-periventricularis and the nucleus lateralis tuberis. The nucleus preopticus-periventricularis consists of the nucleus periventricularis and the nucleus preopticus consisting of a few sparse multipolar neurons in the rostral part and numerous cells closely packed and arranged in several layers in its aboral part. The nucleus lateralis tuberis is located in the ventral-lateral area of the diencephalon and is made up of a number of large multipolar neurones. Four different polyclonal primary antibodies against salmon (sGnRH, chicken (cGnRH-II (cGnRH-II 675, cGnRH-II 6 and sea bream (sbGnRH were employed in the immunohistochemical experiments. No immunoreactive structures were found with anti sbGnRH serum. sGnRH and cGnRH-II antisera revealed immunoreactivity in the perikarya of the olfactory bulbs, preopticus-periventricular nucleus, oculomotor nucleus and midbrain tegmentum. The nucleus lateralis tuberis showed immunostaining only with anti-sGnRH serum. Nerve fibres immunoreactive to cGnRH and sGnRH sera were found in the olfactory bulbs, olfactory nerve and neurohypophysis. The significance of the distribution of the GnRHimmunoreactive neuronal structures is discussed.

  1. Functional Authentication of a Novel Gastropod Gonadotropin-Releasing Hormone Receptor Reveals Unusual Features and Evolutionary Insight

    Kavanaugh, Scott I.


    A gonadotropin-releasing hormone (GnRH)-like molecule was previously identified in a gastropod, Aplysia californica, and named ap-GnRH. In this study, we cloned the full-length cDNA of a putative ap-GnRH receptor (ap-GnRHR) and functionally authenticated this receptor as a bona fide ap-GnRHR. This receptor contains two potential translation start sites, each accompanied by a Kozak sequence, suggesting the translation of a long and a short form of the receptor is possible. The putative ap-GnRHR maintains the conserved structural motifs of GnRHR-like receptors and shares 45% sequence identity with the octopus GnRHR. The expression of the putative ap-GnRHR short form is ubiquitous in all tissues examined, whereas the long form is only expressed in parts of the central nervous system, osphradium, small hermaphroditic duct, and ovotestis. The cDNA encoding the long or the short receptor was transfected into the Drosophila S2 cell line and subject to a radioreceptor assay using 125I-labeled ap-GnRH as the radioligand. Further, the transfected cells were treated with various concentrations of ap-GnRH and measured for the accumulation of cAMP and inositol monophosphate (IP1). Radioreceptor assay revealed that only the long receptor bound specifically to the radioligand. Further, only the long receptor responded to ap-GnRH with an increased accumulation of IP1, but not cAMP. Our studies show that despite the more prevalent expression of the short receptor, only the long receptor is the functional ap-GnRHR. Importantly, this is only the second report on the authentication of a protostome GnRHR, and based on the function and the phylogenetic grouping of ap-GnRHR, we suggest that this receptor is more similar to protostome corazonin receptors than chordate GnRHRs. PMID:27467252

  2. Functional Authentication of a Novel Gastropod Gonadotropin-Releasing Hormone Receptor Reveals Unusual Features and Evolutionary Insight.

    Kavanaugh, Scott I; Tsai, Pei-San


    A gonadotropin-releasing hormone (GnRH)-like molecule was previously identified in a gastropod, Aplysia californica, and named ap-GnRH. In this study, we cloned the full-length cDNA of a putative ap-GnRH receptor (ap-GnRHR) and functionally authenticated this receptor as a bona fide ap-GnRHR. This receptor contains two potential translation start sites, each accompanied by a Kozak sequence, suggesting the translation of a long and a short form of the receptor is possible. The putative ap-GnRHR maintains the conserved structural motifs of GnRHR-like receptors and shares 45% sequence identity with the octopus GnRHR. The expression of the putative ap-GnRHR short form is ubiquitous in all tissues examined, whereas the long form is only expressed in parts of the central nervous system, osphradium, small hermaphroditic duct, and ovotestis. The cDNA encoding the long or the short receptor was transfected into the Drosophila S2 cell line and subject to a radioreceptor assay using 125I-labeled ap-GnRH as the radioligand. Further, the transfected cells were treated with various concentrations of ap-GnRH and measured for the accumulation of cAMP and inositol monophosphate (IP1). Radioreceptor assay revealed that only the long receptor bound specifically to the radioligand. Further, only the long receptor responded to ap-GnRH with an increased accumulation of IP1, but not cAMP. Our studies show that despite the more prevalent expression of the short receptor, only the long receptor is the functional ap-GnRHR. Importantly, this is only the second report on the authentication of a protostome GnRHR, and based on the function and the phylogenetic grouping of ap-GnRHR, we suggest that this receptor is more similar to protostome corazonin receptors than chordate GnRHRs.

  3. Gonadotropin-releasing hormone (GnRH) variants in a lizard brain: is mammalian GnRH being expressed?

    Montaner, A D; Gonzalez, O; Paz, D A; Affanni, J M; Somoza, G M


    In reptiles as in other vertebrates, multiple forms of gonadotropin-releasing hormone (GnRH) within a single brain have been identified. In this group the following GnRH molecular variants have been characterized either by direct or indirect methods: chicken GnRH I (cGnRH-I), chicken GnRH II (cGnRH-II), salmon GnRH (sGnRH) and several unidentified GnRH-like forms. In the present study GnRH variants were investigated in brain extracts of the lizard Tupinambis teguixin (= T. merinae) by combining high-performance liquid chromatography (RP-HPLC) followed by radioimmunoassays (RIA). Two peaks showing GnRH immunoreactivity with the elution position of synthetic mammalian GnRH (mGnRH) and cGnRH-II were detected. Both peaks were further analyzed with different radioimmunoassay systems specific for mGnRH, cGnRH-I, and cGnRH-II. Pooled fractions corresponding to the first eluting peak showed no crossreactivity when analyzed with a cGnRH-I specific assay and logit-log displacement curves were not significantly different from those of synthetic mGnRH with homologous RIA systems. The second peak showed immunological characteristics of cGnRH-II when analyzed with a specific antiserum. The first ir-GnRH peak was selected for further RP-HPLC purification showing similar chromatographic behavior as mGnRH synthetic standard. We demonstrated the absence of cGnRH-I in this lizard using well-characterized antisera.

  4. The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane.

    Michelle Re

    Full Text Available The mammalian type I gonadotropin releasing hormone receptor (GnRH-R is a structurally unique G protein-coupled receptor (GPCR that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME. Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor.

  5. Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer

    Jeremy YC Teoh


    Full Text Available We investigated the cardiovascular thrombotic risk after surgical castration (SC versus gonadotropin-releasing hormone agonists (GnRHa in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3 ± 7.5 years was significantly higher than the GnRHa group (71.8 ± 8.3 years (P < 0.001. There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis (P = 0.014. Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P< 0.001, hyperlipidemia (HR 2.455, 95% CI 1.53-3.93, P< 0.001, and SC (HR 1.648, 95% CI 1.05-2.59, P= 0.031 were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

  6. The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane.

    Re, Michelle; Pampillo, Macarena; Savard, Martin; Dubuc, Céléna; McArdle, Craig A; Millar, Robert P; Conn, P Michael; Gobeil, Fernand; Bhattacharya, Moshmi; Babwah, Andy V


    The mammalian type I gonadotropin releasing hormone receptor (GnRH-R) is a structurally unique G protein-coupled receptor (GPCR) that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME). Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER) leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS) in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor.

  7. Assessing the adequacy of gonadotropin-releasing hormone agonist leuprolide to trigger oocyte maturation and management of inadequate response.

    Chang, Frank E; Beall, Stephanie A; Cox, Jeris M; Richter, Kevin S; DeCherney, Alan H; Levy, Michael J


    To compare outcomes of in vitro fertilization (IVF) cycles with adequate versus inadequate response to the gonadotropin-releasing hormone (GnRH) agonist trigger rescued with the use of human chorionic gonadotropin (hCG) retrigger, and to identify risk factors associated with an inadequate trigger. Retrospective cohort study. Private practice. Women at high risk for ovarian hyperstimulation syndrome who underwent an autologous IVF cycle and used GnRH agonist to trigger oocyte maturation before oocyte retrieval. Patients were triggered with GnRH agonist for final oocyte maturation before retrieval. Patients with an inadequate response, defined by low post-trigger serum LH and P concentrations or failure to recover oocytes after aspiration of several follicles, were retriggered with hCG. Number of oocytes retrieved, fertilization rate, clinical pregnancy, and live birth. Two percent of patients triggered with GnRH agonist had an inadequate response and were retriggered with hCG. There was no statistically significant difference in clinical outcomes between the cycles that were retriggered with hCG and successful GnRH agonist triggers. Low body mass index, low baseline LH, and higher total dosage of gonadotropins required for stimulation were associated with an increased risk of having an inadequate response to the GnRH agonist trigger. A small minority of patients triggered with GnRH agonist had an inadequate response. Rescheduling of oocyte retrieval after hCG retrigger yielded similar IVF outcomes. Evaluation of trigger response based on serum LH and P concentrations is time dependent. Patient characteristics suggestive of hypothalamic hypofunction were predictive of an inadequate response to the GnRH agonist trigger. Copyright © 2016 American Society for Reproductive Medicine. All rights reserved.

  8. Effects of administration of gonadotropin-releasing hormone at artificial insemination on conception rates in dairy cows.

    Shephard, R W; Morton, J M; Norman, S T


    A controlled trial investigating the effect on conception of administration of 250 μg of gonadotropin-releasing hormone (GnRH) at artificial insemination (AI) in dairy cows in seasonal or split calving herds was conducted. Time of detection of estrus, body condition, extent of estrous expression, treatment, breed, age and milk production from the most recent herd test of the current lactation was recorded. Cows were tested for pregnancy with fetal aging between 35 and 135 days after AI. Sixteen herds provided 2344 spring-calved cows and 3007 inseminations. Logistic regression adjusting for clustering at herd level was used to examine the effect of treatment for first (2344) and second (579) inseminations separately. For first AI, treatment significantly improved conception rate in cows with milk protein concentrations of 3.75% or greater and for cows with milk protein concentrations between 3.00% and 3.50% and less than 40 days calved; increased conception rate from 41.2% to 53.4%. Treatment reduced conception rates in cows with milk protein concentrations of 2.75% or less. Treating only cows identified as responding positively to treatment (11% of all study cows) was estimated to increase first service conception rate in herds from 48.1% to 49.4%. There was no significant effect of treatment on conception to second AI, nor any significant interactions. These findings indicate that GnRH at AI should be limited to the sub-group cows most likely to respond. The positive effect of GnRH at AI may be mediated through improved oocyte maturation and/or improved luteal function, rather than by reducing AI-to-ovulation intervals.

  9. The effects of Bushenhuoxue prescription combined with gonadotropin-releasing hormone analogs on ovarian endometriosis cyst after laparoscopic surgery%补肾活血方联合促性腺激素释放激素类似物对卵巢子宫内膜异位囊肿腹腔镜手术后的影响



    目的:探讨补肾活血方联合促性腺激素释放激素类似物( gonadotropin-releasing hormone analogue,GnRH-a)对卵巢子宫内膜异位囊肿腹腔镜手术后的影响。方法选取2013年2月~2014年5月湖北省中国人民解放军第161医院收治的83例卵巢子宫内膜异位囊肿患者,根据患者意愿分为两组。全部患者采用腹腔镜保守性手术治疗与GnRH-a辅助治疗,研究组同时给予补肾活血方治疗。对比两组患者性激素水平变化,随访1年,对比两组患者复发率、妊娠率、不良反应发生情况。结果研究组总有效率(93.02%)显著高于对照组(72.50%)(P <0.05);两组治疗后雌二醇(estradiol,E2)、促卵泡素(follicle stimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、癌抗原125(cancer antigen 125,CA125)、血管内皮生长因子( vascularendothelia gro wth factor ,VEGF)、视觉模拟评分( visual analogue scale ,VAS)显著降低( P<0.05);研究组治疗后E2、FSH、LH、CA125、VEGF、VAS评分较对照组更低,复发率、不良反应发生率低于对照组,妊娠率高于对照组,差异均有统计学意义( P<0.05)。结论补肾活血方联合GnRH-a辅助腹腔镜手术治疗卵巢子宫内膜异位囊肿,能进一步降低患者性激素水平,降低复发率,提高妊娠率。%Objective To investigate the effect of Bushenhuoxue prescription combined with gonadotropin -releasing hormone analogue(GnRH-a) on ovarian endometriosis after laparoscopic surgery .Methods 83 cases of ovarian endometriosis treated in 161 Hospital of People’s Liberation Army in Hubei from Feb 2013 to May 2013 were chosen.They were divided into two groups by patients ’ own will.all patients were treated by laparoscopic conservative surgery treatment .The two groups were given GnRH -a treatment,and the research group were added Bushenhuoxue prescription treatment

  10. Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

    LIANG Yan; WEI Hong; ZHANG Jianling; HOU Ling; LUO Xiaoping


    In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46 girls with ICPP were treated with GnRHa.Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage,bone age, uterine volume and ovarian size, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics.Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment.The height velocity was decreased significantly from 6.3±1.4 cm/year to 5.8±1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBA/deltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively.The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in diameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients,which disappeared after 6- 12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was

  11. Effect of constant administration of a gonadotropin-releasing hormone agonist on reproductive activity in mares: preliminary evidence on suppression of ovulation during the breeding season.

    Fitzgerald, B P; Peterson, K D; Silvia, P J


    During the breeding season, the effect of constant administration of an agonist analog of gonadotropin-releasing hormone (GnRH; goserelin acetate) on reproductive activity of mares was determined. Twenty-four mares undergoing estrous cycles were allocated at random to 6 groups (n = 4/group) and, on May 29 (day 0), received no treatment (group 1, controls), 120 micrograms (group 2), 360 micrograms (group 3), 600 micrograms (group 4), or 1,200 micrograms (group 5) of GnRH agonist/d for 28 days via a depot implanted subcutaneously. The final group of mares (group 6) was treated with 120 micrograms of GnRH agonist/d for 84 days (3 occasions at 28-day intervals). During a pretreatment period (April 19 to May 29) and for 90 days after initiation of GnRH agonist treatment, follicular development and ovulation were monitored by transrectal ultrasonography of the reproductive tract at 2- to 3-day intervals. On each occasion a blood sample was collected for determination of luteinizing hormone (LH) and progesterone. Estrous behavior was monitored by teasing of mares with a stallion. Initiation of agonist treatment was random, relative to the stage of the estrous cycle, and all mares ovulated within 11 days before or after implantation. In 3 of 4 nontreated control mares, estrous cycles were observed throughout the study, with interovulatory intervals ranging from 18 to 26 days. In the remaining mare, concentration of progesterone was high after asynchronous double ovulation during the pretreatment period, suggestive of persistent corpus luteum.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

    Busby, Ellen R.; Sherwood, Nancy M.


    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that...

  13. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment.

    Park, Chan Woo; Choi, Min Hye; Yang, Kwang Moon; Song, In Ok


    To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following GnRH agonist treatment. This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. GnRH agonist pretreatment increased the stimulation duration (11.5±2.1 days vs. 9.9±2.0 days) and total dose of gonadotropin (3,421±1,141 IU vs. 2,588±1,192 IU), which resulted in a significantly higher number of retrieved oocytes (10.0±8.2 vs. 7.9±6.8, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes (14.3±9.2 vs. 10.0±8.2, p=0.022) with a lower dose of gonadotropin (2,974±1,112 IU vs. 3,421±1,141 IU, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further large-scale prospective studies are required to confirm this result.

  14. Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13. 1-q21. 1 and mouse chromosome 5

    Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. (Harvard Medical School, Boston, MA (United States)); Altherr, M.R. (Los Alamos National Lab., NM (United States))


    The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. The authors have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with the evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction. 22 refs., 2 figs.

  15. Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

    Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard


    Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth.

  16. Effects of leptin on gonadotropin-releasing hormone release from hypothalamic-infundibular explants and gonadotropin release from adenohypophyseal primary cell cultures: further evidence that fully nourished cattle are resistant to leptin.

    Amstalden, M; Harms, P G; Welsh, T H; Randel, R D; Williams, G L


    In rodents and pigs, leptin stimulates the release of gonadotropin-releasing hormone (GnRH) from hypothalamus, gonadotropins from adenohypophyseal (AP) explants and cells, and luteinizing hormone (LH) from full-fed animals. In the current studies, we investigated whether leptin could stimulate the release of GnRH from bovine hypothalamic-infundibular (HYP) explants and gonadotropins from bovine adenohypophyseal cells. In Experiment 1A, HYP explants collected from 17 bulls and seven steers were incubated with Krebs-Ringer bicarbonate buffer (KRB) containing 0, 10, 100, or 1000 ng/ml recombinant ovine leptin (oleptin) for 30 min after a 3-h period of equilibration. None of the doses of leptin affected (P > 0.05) GnRH release into the media. In Experiment 1B, HYP explants collected from six steers were incubated with KRB containing 0 or 1000 ng/ml oleptin for two consecutive 30-min periods and challenged with 60 mM K(+) afterwards. Leptin did not affect (P > 0.05) basal or K(+)-stimulated release of GnRH. In Experiment 2, adenohypophyses from steers were collected at slaughter and cells dispersed and cultured for 4 days. On day 5, cells were treated with media alone (control) or media containing 10(-11), 10(-10), 10(-9), and 10(-8)M oleptin. Three independent replications were performed. None of the doses of leptin stimulated (P > 0.05) the release of LH. Although leptin at 10(-11), 10(-10), and 10(-9)M increased (P release of FSH compared to control-treated cells in one replicate, this effect was not confirmed in the other two replicates. Results support the hypothesis that leptin has limited effects on the release of GnRH and gonadotropins in full-fed cattle and reiterate important species differences in responsiveness to leptin.

  17. Expression of Two Gonadotropin-Releasing Hormone (GnRH) Precursor Genes in Various Tissues of the Japanese Eel and Evolution of GnRH(Endocrinology)

    Kataaki, Okubo; Hiroaki, Suetake; KATSUMI, AIDA; Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo


    We isolated and characterized two distinct cDNAs for mammalian gonadotropin-releasing hormone (mGnRH) and chicken GnRH-ll (cGnRH-ll) precursors from the Japanese eel by rapid amplification of cDNA ends. Each GnRH precursors were composed of a signal peptide, a GnRH decapeptide, a processing site and a GnRH-associated peptide. Northern blot and reverse transcription-polymerase chain reaction analysis revealed that the mGnRH precursor gene is expressed in all tissues tested including the brain,...

  18. Ovarian hyperstimulation syndrome prevention strategies: oral contraceptive pills-dual gonadotropin-releasing hormone agonist suppression with step-down gonadotropin protocols.

    Damario, Mark A


    The identification of patients at high risk for excessive responses to ovarian stimulation for in vitro fertilization and embryo transfer is essential in the tailoring of safe and effective treatment strategies. Known factors associated with increased sensitivity to gonadotropins include polycystic ovary syndrome, young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral follicle count, and high baseline ovarian volume. Although several treatment strategies have been proposed for these patients, this report describes the experience using the dual suppression with gonadotropin step-down protocol. This protocol uses oral contraceptive pretreatment in combination with a long gonadotropin-releasing hormone agonist followed by a programmed step-down in gonadotropin dosing. Hormonal characteristics of dual suppression include an improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower serum androgens, particularly dehydroepiandrosterone sulfate. Clinical characteristics of the protocol include a lower cancellation rate and favorable clinical and ongoing pregnancy rates per initiated cycle while mitigating the risk of OHSS.

  19. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers.

    Haughian, James M; Ginther, O J; Diaz, Francisco J; Wiltbank, Milo C


    Mechanisms regulating gonadotropin surges and gonadotropin requirements for follicle emergence and selection were studied in heifers. Experiment 1 evaluated whether follicular inhibins regulate the preovulatory luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surges elicited by gonadotropin-releasing hormone (GnRH) injection (Hour = 0) and the subsequent periovulatory FSH surge. Treatments included control (n = 6), steroid-depleted bovine follicular fluid (bFF) at Hour -4 (n = 6), and bFF at Hour 6 (n = 6). Gonadotropins in blood were assessed hourly from Hours -6 to 36, and follicle growth tracked by ultrasound. Consistent with inhibin independence, bFF at Hour -4 did not impact the GnRH-induced preovulatory FSH surge, whereas treatment at Hour 6 delayed onset of the periovulatory FSH surge and impeded growth of a new follicular wave. Experiment 2 examined GnRH and estradiol (E2) regulation of the periovulatory FSH surge. Treatment groups were control (n = 8), GnRH-receptor antagonist (GnRHr-ant, n = 8), and E2 + GnRHr-ant (n = 4). GnRHr-ant (acyline) did not reduce the concentrations of FSH during the periovulatory surge and early follicle development (8.0 mm) was prevented by GnRHr-ant. Addition of E2 delayed both the onset of the periovulatory FSH surge and emergence of a follicular wave. Failure to select a dominant follicle in the GnRHr-ant group was associated with reduced concentrations of LH but not FSH. Maximum diameter of F1 in controls (13.3 ± 0.5 mm) was greater than in both GnRHr-ant (7.7 ± 0.3 mm) and E2 + GnRHr-ant (6.7 ± 0.8 mm) groups. Results indicated that the periovulatory FSH surge stems from removal of negative stimuli (follicular E2 and inhibin), but is independent of GnRH stimulation. Emergence and early growth of follicles (until about 8 mm) requires the periovulatory FSH surge but not LH pulses. However, follicular deviation and late-stage growth of a single dominant follicle requires GnRH-dependent LH pulses.

  20. Effects of inorganic and organic manganese supplementation on gonadotropin-releasing hormone-I and follicle-stimulating hormone expression and reproductive performance of broiler breeder hens.

    Xie, Jingjing; Tian, Chuanhuan; Zhu, Yongwen; Zhang, Liyang; Lu, Lin; Luo, Xugang


    Manganese is an essential microelement. Manganese deficiency affects reproduction performance and reproductive hormones in layers. However, little is known about its effects and the possible mechanism in regulating reproduction in broiler breeder hens. In the current study, broiler breeder hens at peak production were fed with diets supplemented with 0, 120, or 240 mg of Mn/kg as MnSO4 or Mn proteinate for 13 wk. Manganese supplementation did not alter egg laying rate, egg weight, fertility, hatchability, or hatchling weight over a 13-wk trial period. However, 240 mg of Mn/kg supplementation significantly increased serum Mn (P Manganese supplements increased the eggshell breaking strength (P < 0.05) without affecting the eggshell thickness. There was no difference in serum cholesterol and estradiol. Expression of follicle-stimulating hormone) and gonadotropin-releasing hormone-I (GnRH-I) genes was significantly elevated by 240 mg of Mn/kg (P < 0.05). Furthermore, inorganic Mn supplementation doubled GnRH-I expression compared with supplementation with the organic form (P < 0.05), although serum Mn was comparable between these 2 supplements. No obvious difference was shown in gene expression of luteinizing hormone, prolactin, GnRH-I receptor, inducible NO synthase, and dopamine receptor D1 in the pituitary as well as tyrosine hydroxylase and inducible NO synthase in the hypothalamus. This suggests that dietary Mn supplementation could improve eggshell quality in the long term. The central mechanism of nontoxic high doses of Mn suggested the transcriptional activation of GnRH-I and follicle-stimulating hormone genes. The central effect of inorganic Mn activating GnRH-I genes compared with the reduced effect by organic Mn could possibly be due to a decreased capacity of the latter passing through the blood-brain barrier.

  1. Antimullerian hormone: prediction of cumulative live birth in gonadotropin-releasing hormone antagonist treatment for in vitro fertilization

    Hamdine, O.; Eijkemans, M.J.; Lentjes, E.G.; Torrance, H.L.; Macklon, N.S.; Fauser, B.C.; Broekmans, F.J.


    OBJECTIVE: To assess the accuracy of antimullerian hormone (AMH) in predicting cumulative live birth rate (CLBR) within 1 year after treatment initiation in GnRH antagonist treatment cycles for in vitro fertilization (IVF). DESIGN: Observational (retrospective) substudy as part of an ongoing

  2. Hormonal induction of spawning in 4 species of frogs by coinjection with a gonadotropin-releasing hormone agonist and a dopamine antagonist

    Wignall Jacqui


    Full Text Available Abstract Background It is well known that many anurans do not reproduce easily in captivity. Some methods are based on administration of mammalian hormones such as human chorionic gonadotropin, which are not effective in many frogs. There is a need for simple, cost-effective alternative techniques to induce spawning. Methods Our new method is based on the injection of a combination of a gonadotropin-releasing hormone (GnRH agonist and a dopamine antagonist. We have named this formulation AMPHIPLEX, which is derived from the combination of the words amphibian and amplexus. This name refers to the specific reproductive behavior of frogs when the male mounts and clasps the female to induce ovulation and to fertilize the eggs as they are laid. Results We describe the use of the method and demonstrate its applicability for captive breeding in 3 different anuran families. We tested several combinations of GnRH agonists with dopamine antagonists using Lithobates pipiens. The combination of des-Gly10, D-Ala6, Pro-LHRH (0.4 microrams/g body weight and metoclopramide (10 micrograms/g BWt. MET was most effective. It was used in-season, after short-term captivity and in frogs artificially hibernated under laboratory conditions. The AMPHIPLEX method was also effective in 3 Argentinian frogs, Ceratophrys ornata, Ceratophrys cranwelli and Odontophrynus americanus. Conclusion Our approach offers some advantages over other hormonally-based techniques. Both sexes are injected only once and at the same time, reducing handling stress. AMPHIPLEX is a new reproductive management tool for captive breeding in Anura.

  3. Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction.

    Park, Hyo Young; Lee, Min Young; Jeong, Hyo Young; Rho, Yong Sook; Song, Sang Jin; Choi, Bum-Chae


    To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS.

  4. Hormonal induction of spawning in 4 species of frogs by coinjection with a gonadotropin-releasing hormone agonist and a dopamine antagonist


    Background It is well known that many anurans do not reproduce easily in captivity. Some methods are based on administration of mammalian hormones such as human chorionic gonadotropin, which are not effective in many frogs. There is a need for simple, cost-effective alternative techniques to induce spawning. Methods Our new method is based on the injection of a combination of a gonadotropin-releasing hormone (GnRH) agonist and a dopamine antagonist. We have named this formulation AMPHIPLEX, which is derived from the combination of the words amphibian and amplexus. This name refers to the specific reproductive behavior of frogs when the male mounts and clasps the female to induce ovulation and to fertilize the eggs as they are laid. Results We describe the use of the method and demonstrate its applicability for captive breeding in 3 different anuran families. We tested several combinations of GnRH agonists with dopamine antagonists using Lithobates pipiens. The combination of des-Gly10, D-Ala6, Pro-LHRH (0.4 microrams/g body weight) and metoclopramide (10 micrograms/g BWt. MET) was most effective. It was used in-season, after short-term captivity and in frogs artificially hibernated under laboratory conditions. The AMPHIPLEX method was also effective in 3 Argentinian frogs, Ceratophrys ornata, Ceratophrys cranwelli and Odontophrynus americanus. Conclusion Our approach offers some advantages over other hormonally-based techniques. Both sexes are injected only once and at the same time, reducing handling stress. AMPHIPLEX is a new reproductive management tool for captive breeding in Anura. PMID:20398399

  5. Blood-brain barrier to peptides: (/sup 3/H)gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    Ermisch, A.; Ruehle, H.J. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften); Klauschenz, E.; Kretzschmar, R. (Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)


    After intracarotid injection of (/sup 3/H)gonadotropin-releasing hormone ((/sup 3/H)GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g/sup -1/ of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of (/sup 3/H)GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated (/sup 3/H)OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of (/sup 3/H)GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for (/sup 3/H)GnRH are similar to those for other peptides so far investigated.

  6. Gonadotropin-releasing hormone (Gn-RH) in striped mullet (Mugil cephalus), milkfish (Chanos chanos), and rainbow trout (Salmo gairdneri): comparison with salmon Gn-RH

    Sherwood, N.M.; Harvey, B.; Brownstein, M.J.; Eiden, L.E.


    Immunoreactive gonadotropin-releasing hormone (Gn-RH) was extracted from brains of striped mullet, milkfish, rainbow trout, and chum salmon with acetone/HCl and petroleum ether. High pressure liquid chromatography and cross-reactivity studies show mullet, milkfish, and trout brains to contain a peptide chromatographically and immunologically identical to synthetic salmon Gn-RH, while the mammalian form of Gn-RH is detectable in none of these fishes. Gn-RH is present in immature 7-month-old and 4-year-old milkfish. A second immunoreactive peptide is separable by HPLC in all the fish studied. This early-eluting form of Gn-RH is unlikely to be a precursor; its cross-reactivity with antisera R-42 and number185 suggests that any modification is in the C-terminal region. Several possible roles for this peptide are advanced.

  7. Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis: Effects on Bone Mineral Density

    Cho, Young Hwa; Um, Mi Jung; Kim, Suk Jin; Kim, Soo Ah


    Objectives To evaluate the efficacy of raloxifene in preventing bone loss associated with long term gonadotropin-releasing hormone agonist (GnRH-a) administration. Methods Twenty-two premenopausal women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3.75 mg/4 weeks, for 48 weeks. Bone mineral density (BMD) was evaluated at admission, and after 12 treatment cycles. Results At cycle 12 of GnRH-a plus raloxifene treatment, lumbar spine, trochanter femoral neck, and Ward's BMD differed from before the treatment. A year after treatment, the lumbar spine and trochanter decreased slightly, but were not significantly different. Conclusions Our study shows that the administration of GnRH-a plus raloxifene in pre-menopausal women with severe endometriosis, is an effective long-term treatment to prevent bone loss. PMID:28119898

  8. Detection of Messenger RNA for Gonadotropin-Releasing Hormone (GnRH) but not for GnRH Receptors in Rat Pancreas

    王雷; 谢莉萍; 黄威权; 张荣庆


    Although gonadotropin-releasing hormone (GnRH), GnRH-like molecule, and GnRH receptor (GnRH-R) have been reported to exist in several tissues other than brain or anterior pituitary, there are no reports concerning GnRH or GnRH-R gene expression in a normal pancreatic gland. In order to define the production of GnRH as well as GnRH-R in the pancreatic gland, we examined their gene expression in various developmental stages of rat pancreas using the reverse transcriptase-polymerase chain reaction (RT-PCR).GnRH mRNA transcripts were found in pancreas of male and female rats at different ages, expressing at about the same level, whereas GnRH-R mRNA transcripts could not be detected in any rat pancreatic gland samples. These results suggest a possible biological role of GnRH in rodent pancreas.

  9. Cytoplasmic kinases downstream of GPR30 suppress gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone secretion from bovine anterior pituitary cells.

    Rudolf, Faidiban O; Kadokawa, Hiroya


    GPR30 is known as a membrane receptor for picomolar concentrations of estradiol. The GPR30-specific agonist G1 causes a rapid, non-genomic suppression of gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion from bovine anterior pituitary (AP) cells. A few studies have recently clarified that protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (pERK) might be involved in cytoplasmic signaling pathways of GPR30 in other cells. Therefore, we tested the hypothesis that PKA and ERK kinase (MEK) are important cytoplasmic mediators for GPR30-associated non-genomic suppression of GnRH-induced LH secretion from bovine AP cells. Bovine AP cells (n = 8) were cultured for 3 days under steroid-free conditions. The AP cells were previously treated for 30 min with one of the following: 5000 nM of PKA inhibitor (H89), 1000 nM of MEK inhibitor (U0126), or a combination of H89 and U0126. Next, the AP cells were treated with 0.01 nM estradiol for 5 min before GnRH stimulation. Estradiol treatment without inhibitor pretreatment significantly suppressed GnRH-induced LH secretion (P < 0.01). In contrast, estradiol treatment after pretreatment with H89, U0126 or their combination had no suppressive effect on GnRH-induced LH secretion. The inhibitors also inhibited the G1 suppression of GnRH-induced LH secretion. Therefore, these data supported the hypothesis that PKA and MEK (thus, also pERK) are the intracellular mediators downstream of GPR30 that induce the non-genomic suppression of GnRH-induced LH secretion from bovine AP cells by estradiol or G1.

  10. Polymorphisms in luteinizing hormone receptor and hypothalamic gonadotropin-releasing hormone genes and their effects on sperm quality traits in Chinese Holstein bulls.

    Sun, Li-Ping; Du, Qing-Zhi; Song, Ya-Pan; Yu, Jun-Na; Wang, Shu-Juan; Sang, Lei; Song, Luo-Wen; Yue, Yao-Min; Lian, Yu-Ze; Zhang, Sheng-Li; Hua, Guo-Hua; Zhang, Shu-Jun; Yang, Li-Guo


    Genes of hypothalamic-pituitary-gonadal axis play a key role in male reproductive performance. This study evaluated the polymorphisms of luteinizing hormone receptor (LHR) and hypothalamic gonadotropin-releasing hormone (GnRH) genes and their effects on sperm quality traits including semen volume per ejaculate (VOL), sperm density (SD), fresh sperm motility (FSM), thawed sperm motility (TSM), acrosome integrity rate (AIR), and abnormal sperm rate (ASR) collected from 205 Chinese Hostein bulls. The study bulls consisted of 205 mature Chinese Holstein, 27 Simmental, 28 Charolais, and 14 German yellow cattle. One single nucleotide polymorphism (SNP) (A883G) in exon 2 of GnRH and two SNPs (A51703G and G51656T) in intron 9 of LHR were identified in 274 bulls. Analysis of variance in 205 Chinese Holstein bulls showed that age had significant effect on both SD and FSM (P bulls with AG genotype had higher FSM than bulls with AA and GG genotype in LHR at 51,703 locus (P bulls with GG genotype had higher SD than bulls with TT genotype in LHR at G51656T locus (P < 0.10). Phenotypic correlation among the traits revealed that significant negative correlations were observed between ASR and AIR (r = -0.736, P < 0.01), ASR and AIR (r = -0.500, P < 0.01). There were moderate positive correlations between VOL and SD (r = 0.422, P < 0.01), as well as FSM (r = 0.411, P < 0.01). In conclusion, LHR may be a potential marker for sperm quality of SD and FSM.

  11. The effect of dietary monensin on th luteinizing hormone response of prepuberal heifers given a multiple gonadotropin-releasing hormone challenge.

    Randel, R D; Rhodes, R C


    Ten prepuberal Simmental X Brahman-Hereford heifers (average weight 208 +/- 4 kg) were randomly assigned to receive either 2.7 kg/head/day of ground milo containing 0 mg monensin sodium (C) or 2.7 kg/head/day of ground milo containing 200 mg monensin sodium (M). Both groups of animals (n = 5) received Coastal bermudagrass hay ad libitum throughout the trial. On day 21 of the feeding period all heifers were fitted with jugular cannulas. Immediately after cannulation, the heifers were injected IM with 100 microgram of gonadotropin-releasing hormone (GnRH) and blood was collected every 10 min for 4 hours. Four hours after the first GnRH challenge, a second 100-microgram GnRH injection was administered, and blood samples were collected at 10-min intervals for an additional 5 hours. Serum was stored at -20 C until radioimmunoassayed for luteinizing hormone (LH). The amount of LH released after each GnRH injection was greater in the heifers fed M than in the controls (P less than .05). Peak LH after the first GnRH challenge was greater (P less than .05) in heifers fed M than in controls. The area under th first GnRH induced LH curve tended (P less than .20) to be greater for the M group than for the controls. Peak LH concentration was greater in heifers fed M than in control heifers, as the duration (P less than .05) and area under the second GnRH-induced LH curve. In prepuberal heifers, dietary monensin appears to increase hypophyseal capability of releasing LH after a first and second GnRH challenge.

  12. Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of fasting.

    Tuziak, Sarah M; Volkoff, Hélène


    Melanin-concentrating hormone (MCH) is classically known for its role in regulating teleost fish skin color change for environmental adaptation. Recent evidence suggests that MCH also has appetite-stimulating properties. The gonadotropin-releasing hormone (GnRH) peptide family has dual roles in endocrine control of reproduction and energy status in fish. Atlantic cod (Gadus morhua) are a commercially important aquaculture species inhabiting the shores of Atlantic Canada. In this study, we examine MCH and GnRH transcript expression profiles during early development as well as in central and peripheral tissues and quantify juvenile Atlantic cod MCH and GnRH hypothalamic mRNA expressions following food deprivation. MCH and GnRH3 cDNAs are maternally deposited into cod eggs, while MCH has variable expression throughout early development. GnRH2 and GnRH3 mRNAs "turn-on" during mid-segmentation once the brain is fully developed. For both MCH and GnRH, highest expression appears during the exogenous feeding stages, perhaps supporting their functions as appetite regulators during early development. MCH and GnRH transcripts are found in brain regions related to appetite regulation (telencephalon/preoptic area, optic tectum/thalamus, hypothalamus), as well as the pituitary gland and the stomach, suggesting a peripheral function in food intake regulation. Atlantic cod MCH mRNA is upregulated during fasting, while GnRH2 and GnRH3 transcripts do not appear to be influenced by food deprivation. In conclusion, MCH might be involved in stimulating food intake in juvenile Atlantic cod, while GnRHs may play a more significant role in appetite regulation during early development.

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

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


    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.

  14. Effects of early vaccination with a gonadotropin releasing factor analog-diphtheria toxoid conjugate on boar taint and growth performance of male pigs.

    Kantas, D; Papatsiros, V; Tassis, P; Tzika, E; Pearce, M C; Wilson, S


    The aim of this study was to evaluate safety (in terms of detecting possible adverse clinical effects attributable to vaccination), efficacy, and effects on growth performance of a gonadotropin releasing factor analog-diphtheria toxoid conjugate (commercially distributed as Improvac; Zoetis, Zaventem, Belgium) in male pigs raised in a commercial Greek farm. A total of 1,230 male pigs was enrolled in 16 weekly batches and allocated to 3 groups: barrows (castrated on the next day after birth [study Day 0]), pigs vaccinated with the above-mentioned product, and intact boars. Vaccinated pigs were injected subcutaneously with 2 mL of the anti-gonadotropin releasing factor (GnRF) vaccine at 9 to 11 wk of age (60-78 d) and 15 to 17 wk of age (102-120 d) and slaughtered at 22 to 25 wk of age (152-176 d). No clinical abnormalities or adverse events attributable to vaccination occurred. Mean BW of vaccinated pigs was 6% greater compared with barrows at slaughter (P vaccinated pigs had greater ADG than barrows from castration to slaughter (8%). In detail, a lower ADG from first to second vaccination (-12%; P vaccination to slaughter (P vaccinated pigs and intact boars was not significantly different throughout the study, except from first to second vaccination (boars greater; P = 0.0059) and second vaccination to slaughter (vaccinates greater; P = 0.0390). Feed conversion ratio of barrows was 11 and 8% greater compared with vaccinated pigs (P = 0.0005) and boars (P = 0.0062) from first to second vaccination but was 23 to 26% lower compared with vaccinated pigs (P vaccination to slaughter and 7 to 9.5% lower from the second vaccination to slaughter (P = 0.0029 and P = 0.0003 for vaccinates and intact boars, respectively). At slaughter, the belly fat androstenone concentration of all vaccinated pigs and 64% of intact boars was below 200 ng/g. Belly fat skatole concentration was below 20 ng/g in samples from all groups. In conclusion, vaccination against GnRF using the Gn

  15. Temporal changes in serum luteinizing hormone following ovariohysterectomy and gonadotropin-releasing hormone vaccination in domestic cats.

    Bateman, H L; Vansandt, L M; Newsom, J; Swanson, W F


    Measurement of circulating luteinizing hormone (LH) concentrations in cats and temporal changes following ovariohysterectomy (OHE) or possibly GnRH vaccination may be informative for assessing their fertility, contraception or sterilization status. In this study, serum LH concentrations were measured in domestic cats (n = 6) immediately prior to and up to 120 days post-OHE. Basal LH concentrations of females previously subjected to OHE (n = 4; ~1.5 years post-OHE) were compared pre- and post-vaccination with a GnRH immunocontraceptive, and to LH concentrations in intact females. Basal serum LH concentrations (2.67 ± 0.43 ng/ml; mean ± SEM) in intact females increased (p < .01) by 30 days post-OHE (5.65 ± 0.87 ng/ml) but then declined (p < .05) to pre-OHE levels (mean range, 3.26-3.62 ng/ml) at days 60-120 post-OHE. Serum LH (3.84 ± 0.51 ng/ml) in four females ~1.5 years after OHE tended to be higher (p = .10) than those of intact females prior to OHE. Three months following first or second GnRH immunocontraceptive vaccine treatment, serum LH values in females previously subjected to OHE decreased (p < .05) to concentrations similar to those observed in intact females. Our preliminary results suggest that OHE of domestic cats causes a marked increase in basal LH levels within the first few weeks after ovariohysterectomy followed by a return to pre-OHE basal values over the next several months. Reduced LH concentrations after GnRH vaccine may indicate the effectiveness of the immunocontraceptive in reducing the circulating levels of GnRH, thereby reducing secretion of LH. © 2016 Blackwell Verlag GmbH.

  16. Effects of MboII and BspMI polymorphisms in the gonadotropin releasing hormone receptor (GnRHR) gene on sperm quality in Holstein bulls.

    Yang, Wu-Cai; Tang, Ke-Qiong; Yu, Jun-Na; Zhang, Chun-Yan; Zhang, Xiao-Xia; Yang, Li-Guo


    The hypothalamic gonadotropin-releasing hormone receptor (GnRHR) plays an essential physiological role in reproductive function, which triggers the synthesis and release of luteinizing hormone and follicle stimulating hormone in the pituitary. The objective of this study was to investigate the effects of polymorphisms of GnRHR gene on the quality of fresh and frozen semen in Holstein bulls. The PCR-RFLP method was applied to detect G286A and T340C transitions determining MboII and BspMI polymorphisms, respectively, in the exon I of bovine GnRHR gene and evaluated its associations with sperm quality traits in 131 Holstein bulls. In polymorphic locus 286, bulls with the GA genotype had significantly higher sperm motility in frozen semen (FMOT) than GG genotype (P bulls with heterozygote CT genotype had significantly higher sperm motility (MOT), semen volume per ejaculate (VOL), and lower abnormal spermatozoa rate (ASR) than homozygote TT genotype (P Bulls contained one A allele or C allele had a favorable, positive effect on sperm quality traits. These results indicate that GnRHR gene can be a potential marker for improving sperm quality traits, and imply that bulls with GA or CT genotype should be selected in breeding program.

  17. Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

    Park, Jina; Kim, Jae Hyun


    Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. No statistical difference in BMI z-score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all Presistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z-scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z-scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

  18. The effects of serotonin, dopamine, gonadotropin-releasing hormones, and corazonin, on the androgenic gland of the giant freshwater prawn, Macrobrachium rosenbergii.

    Siangcham, Tanapan; Tinikul, Yotsawan; Poljaroen, Jaruwan; Sroyraya, Morakot; Changklungmoa, Narin; Phoungpetchara, Ittipon; Kankuan, Wilairat; Sumpownon, Chanudporn; Wanichanon, Chaitip; Hanna, Peter J; Sobhon, Prasert


    Neurotransmitters and neurohormones are agents that control gonad maturation in decapod crustaceans. Of these, serotonin (5-HT) and dopamine (DA) are neurotransmitters with known antagonist roles in female reproduction, whilst gonadotropin-releasing hormones (GnRHs) and corazonin (Crz) are neurohormones that exercise both positive and negative controls in some invertebrates. However, the effects of these agents on the androgenic gland (AG), which controls testicular maturation and male sex development in decapods, via insulin-like androgenic gland hormone (IAG), are unknown. Therefore, we set out to assay the effects of 5-HT, DA, l-GnRH-III, oct-GnRH and Crz, on the AG of small male Macrobrachium rosenbergii (Mr), using histological studies, a BrdU proliferative cell assay, immunofluorescence of Mr-IAG, and ELISA of Mr-IAG. The results showed stimulatory effects by 5-HT and l-GnRH-III through significant increases in AG size, proliferation of AG cells, and Mr-IAG production (Prosenbergii, as they induce increases in AG and testicular size, IAG production, and spermatogenesis. The mechanisms by which these occur are part of our on-going research.


    L. Safdarian


    Full Text Available There is a challenging debate on the effect of premature luteinization on the clinical outcome of ‘controlled ovarian hyperstimulation' (COH using long ‘gonadotropin-releasing hormone agonist' (GnRHa cycles. Premature luteinization is defined as late follicular progesterone/estradiol ratio more than 1 on the day of human chorionic gonadotropin (HCG administration. We carried out a retrospective case-control study on 75 conceived cases versus 75 not-conceived control women, receiving long GnRHa cycles in their first cycle of treatment. Premature luteinization developed in 15% of the case group vs. 22% of the control group. Neither the late follicular progesterone/estradiol (P/E2 ratio was significantly different between the two groups, nor the day 3 follicle stimulating hormone (FSH, serum estradiol level on the HCG day, total amount of human menopausal gonadotropins ampoules, number of follicles, retrieved oocytes and transferred embryos. Endometrial thickness was significantly more in the pregnant women than in the non-pregnant group. Premature luteinization seems not to adversely affect the clinical outcome of COH.

  20. Molecular cloning, characterization, and expression analysis of a gonadotropin-releasing hormone-like cDNA in the clam, Ruditapes philippinarum.

    Song, Ying; Miao, Jingjing; Cai, Yuefeng; Pan, Luqing


    Gonadotropin-releasing hormone (GnRH) is a key neuropeptide regulating reproduction in vertebrates. In the present study, we have cloned and identified the cDNA sequence of the prepro-GnRH (rp-GnRH) in the Manila clam Ruditapes philippinarum. The open reading frame encodes a protein of 94 amino acids, which consists of a signal peptide, a GnRH dodecapeptide, a cleavage site, and a GnRH-associated peptide. These deduced peptides were highly homologous to that reported for other molluscs. We used temperature control to promote gonadal development of the clams. The mRNA expression of rp-GnRH in the visceral ganglia from clams at different reproductive stages was determined by quantitative RT-PCR. The levels of steroids progesterone (P), testosterone (T), and estradiol-17β (E2) in the hemolymph of the corresponding clam were measured by ELISA. The rp-GnRH mRNA was highly expressed at the gonadal early development stage. Concentrations of P, T, and E2 also increased at the early development stage in both sexes. Positive significant correlations between rp-GnRH expression and P content as well as between rp-GnRH expression and T content were observed throughout the gonadal maturation. The results from this study may help to better understand the physiological functions of the native forms of GnRH-like peptides and the actions of GnRH on sex steroids release in bivalve molluscs.

  1. Resurgence of Minimal Stimulation In Vitro Fertilization with A Protocol Consisting of Gonadotropin Releasing Hormone-Agonist Trigger and Vitrified-Thawed Embryo Transfer

    Zhang John


    Full Text Available Minimal stimulation in vitro fertilization (mini-IVF consists of a gentle controlled ovarian stimulation that aims to produce a maximum of five to six oocytes. There is a misbelief that mini-IVF severely compromises pregnancy and live birth rates. An appraisal of the literature pertaining to studies on mini-IVF protocols was performed. The advantages of minimal stimulation protocols are reported here with a focus on the use of clomiphene citrate (CC, gonadotropin releasing hormone (GnRH ago- nist trigger for oocyte maturation, and freeze-all embryo strategy. Literature review and the author’s own center data suggest that minimal ovarian stimulation protocols with GnRH agonist trigger and freeze-all embryo strategy along with single embryo transfer produce a reasonable clinical pregnancy and live birth rates in both good and poor responders. Additionally, mini-IVF offers numerous advantages such as: i. Reduction in cost and stress with fewer office visits, needle sticks, and ultrasounds, and ii. Reduction in the incidence of ovarian hyperstimulation syndrome (OHSS. Mini-IVF is re-emerging as a solution for some of the problems associated with conventional IVF, such as OHSS, cost, and patient discomfort.

  2. Testicular Dnmt3 expression and global DNA methylation are down-regulated by gonadotropin releasing hormones in the ricefield eel Monopterus albus

    Zhang, Yize; Sun, Xin; Zhang, Lihong; Zhang, Weimin


    In vertebrates, DNA methyltransferase 3 (Dnmt3) homologues are responsible for de novo DNA methylation and play important roles in germ cell development. In the present study, four dnmt3 genes, dnmt3aa, dnmt3ab, dnmt3ba and dnmt3bb.1, were identified in ricefield eels. Real-time quantitative PCR analysis showed that all four dnmt3 mRNAs were detected broadly in tissues examined, with testicular expression at relatively high levels. In the testis, immunostaining for all four Dnmt3 forms was mainly localized to spermatocytes, which also contained highly methylated DNA. All three forms of Gonadotropin-releasing hormone (Gnrh) in the ricefield eel were shown to decrease the expression of dnmt3 genes in the in vitro incubated testicular fragments through cAMP and IP3/Ca2+ pathways. Moreover, in vivo treatment of male fish with three forms of Gnrh decreased significantly the testicular Dnmt3 expression at both mRNA and protein levels, and the global DNA methylation levels. These results suggest that the expression of Dnmt3 and global DNA methylation in the testis of ricefield eels are potentially down-regulated by Gnrh, and reveal a novel regulatory mechanism of testicular Dnmt3 expression in vertebrates. PMID:28225069

  3. A gonadotropin-releasing hormone-like molecule modulates the activity of diverse central neurons in a gastropod mollusk, Aplysia californica

    Biao eSun


    Full Text Available In vertebrates, gonadotropin-releasing hormone (GnRH is a crucial decapeptide that activates the hypothalamic-pituitary-gonadal (HPG axis to ensure successful reproduction. Recently, a GnRH-like molecule has been isolated from a gastropod mollusk, Aplysia californica. This GnRH (ap-GnRH is deduced to be an undecapeptide, and its function remains to be explored. Our previous study demonstrated that ap-GnRH did not stimulate a range of reproductive parameters. Instead, it affected acute behavioral and locomotive changes unrelated to reproduction. In this study, we used electrophysiology and retrograde tracing to further explore the central role of ap-GnRH. Sharp electrode intracellular recordings revealed that ap-GnRH had diverse effects on central neurons that ranged from excitatory, inhibitory, to the alteration of membrane potential. Unexpectedly, extracellular recordings revealed that ap-GnRH suppressed the onset of electrical afterdischarge (AD in bag cell neurons, suggesting an inhibitory effect on female reproduction. Lastly, using immunocytochemistry (ICC coupled with nickel-backfill, we demonstrated that some ap-GnRH neurons projected to efferent nerves known to innervate the foot and parapodia, suggesting ap-GnRH may directly modulate the motor output of these peripheral tissues. Overall, our results suggested that in A. californica, ap-GnRH more likely functioned as a central modulator of complex behavior and motor regulation rather than as a conventional reproductive stimulator.

  4. Local duplication of gonadotropin-releasing hormone (GnRH receptor before two rounds of whole genome duplication and origin of the mammalian GnRH receptor.

    Fatemeh Ameri Sefideh

    Full Text Available Gonadotropin-releasing hormone (GnRH and the GnRH receptor (GnRHR play an important role in vertebrate reproduction. Although many GnRHR genes have been identified in a large variety of vertebrate species, the evolutionary history of GnRHR in vertebrates is unclear. To trace the evolutionary origin of GnRHR we examined the conserved synteny of chromosomes harboring GnRHR genes and matched the genes to linkage groups of reconstructed vertebrate ancestor chromosomes. Consistent with the phylogenetic tree, three pairs of GnRHR subtypes were identified in three paralogous linkage groups, indicating that an ancestral pair emerged through local duplication before two rounds of whole genome duplication (2R. The 2R then led to the generation of six subtypes of GnRHR. Some subtypes were lost during vertebrate evolution after the divergence of teleosts and tetrapods. One subtype includes mammalian GnRHR and a coelacanth GnRHR that showed the greatest response to GnRH1 among the three types of GnRH. This study provides new insight into the evolutionary relationship of vertebrate GnRHRs.

  5. Associations of Gonadotropin-Releasing Hormone Receptor (GnRHR) and Neuropeptide Y (NPY) Genes' Polymorphisms with Egg-Laying Traits in Wenchang Chicken

    WU Xu; ZHU Wen-qi; LI Hui-fang; YAN Mei-jiao; TANG Qing-ping; CHEN Kuan-wei; WANG Jin-yu; GAO Yu-shi; TU Yun-jie; YU Ya-bo


    Single nucleotide polymorphisms (SNP) of chicken gonadotropin-releasing hormone receptor (GnRHR) and neuropeptide Y (NPY) were selected to identify the genotypes of Wenchang (Chinese indigenous breed) chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production (NE), average days of continual laying (ADCL), and number of double-yolked eggs (DYE) traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 (Bpu1102 Ⅰ A) and 0.31 (Bpu1102 Ⅰ a) and for NPY 0.46 (Dra Ⅰ B) and 0.54 (Dra Ⅰ b). Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes' marker were found: for GnRHR and number of eggs (dominant; t= 2.67, df= 116) and NPY and number of eggs (additive; t= 1.97, df= 116). The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.

  6. Induction of castration by immunization of male dogs with recombinant gonadotropin-releasing hormone (GnRH)-canine distemper virus (CDV) T helper cell epitope p35.

    Jung, Mi-Jeong; Moon, Young-Chan; Cho, Ik-Hyun; Yeh, Jung-Yong; Kim, Sun-Eui; Chang, Wha-Seok; Park, Seung-Young; Song, Chang-Seon; Kim, Hwi-Yool; Park, Keun-Kyu; McOrist, Steven; Choi, In-Soo; Lee, Joong-Bok


    Immunocastration is a considerable alternative to a surgical castration method especially in male animal species for alleviating unwanted male behaviors and characteristics. Induction of high titer of antibody specific for gonadotropin-releasing hormone (GnRH) correlates with the regression of testes. Fusion proteins composed of canine GnRH and T helper (Th) cell epitope p35 originated from canine distemper virus (CDV) F protein and goat rotavirus VP6 protein were produced in E. coli. When these fusion proteins were injected to male dogs which were previously immunized with CDV vaccine, the fusion protein of GnRH-CDV Th cell epitope p35 induced much higher antibody than that of GnRH-rotavirus VP6 protein or GnRH alone. The degeneration of spermatogenesis was also verified in the male dogs immunized with the fusion protein of GnRH-CDV Th cell epitope p35. These results indicate that canine GnRH conjugated to CDV Th cell epitope p35 acted as a strong immunogen and the antibody to GnRH specifically neutralized GnRH in the testes. This study also implies a potential application of GnRH-based vaccines for immunocastration of male pets.

  7. Assessment of stress levels in girls with central precocious puberty before and during long-acting gonadotropin-releasing hormone agonist treatment: a pilot study.

    Menk, Tais A S; Inácio, Marlene; Macedo, Delanie B; Bessa, Danielle S; Latronico, Ana C; Mendonca, Berenice B; Brito, Vinicius Nahime


    The objective of the study was to determine the stress levels of girls with central precocious puberty (CPP) before and during treatment with a long-acting gonadotropin-releasing hormone agonist (GnRHa). The Child Stress Scale (CSS) was used for 10 unrelated girls with CPP before and after the first year of GnRHa treatment. The CSS is divided into four subscales (physical, psychological, psychological with depressive component and psychophysiological reactions). Through a quantitative analysis, it is possible to classify stress into four stages: alarm, resistance, near-exhaustion and exhaustion. At diagnosis, 90% of the girls showed stress levels scores at the alarm or resistance stage on at least one subscale, mostly in terms of physical and psychological reactions. The mean total stress score was significantly higher before when compared to after GnRHa treatment (43.4±15.6 vs. 28.9±9.7; pstress scores obtained in all subscales, except the one on psychophysiological reactions, were significantly higher before GnRHa treatment. Higher stress levels were a common finding in girls with CPP before treatment. The significant stress level reduction after pubertal suppression reinforces the idea that sexual precocity is a stressful condition in children. The CSS might be a useful tool for psychological assessment of patients with CPP.

  8. Gonadotropin-releasing hormone agonist triggering is effective, even at a low dose, for final oocyte maturation in ART cycles: Case series.

    Gülekli, Bülent; Göde, Funda; Sertkaya, Zerrin; Işık, Ahmet Zeki


    To investigate the efficacy of low-dose gonadotropin-releasing hormone (GnRH) agonist for final oocyte maturation in females undergoing assisted reproductive treatment (ART) cycles. Nine females undergoing ovarian stimulation in a GnRH antagonist protocol who received triptorelin 0.1 mg to trigger final oocyte maturation were included. Treatment outcomes of these patients were compared with those of controls, matched for age and oocyte number (n=14), who received 0.2 mg triptorelin at the same time. The luteal phase was supported with vaginal micronized progesterone and oral estradiol hemihydrate 2 mg twice daily. The mean (±) numbers of retrieved, metaphase II, and fertilized oocytes were 15.66±7.82, 14±7.28, and 10.11±5.86, respectively. The implantation and clinical pregnancy rates were 46.1% and 71.4%, respectively. Of the pregnancies, 2 were live births, 1 was a preterm birth (twins), 2 are on-going, and 2 ended as miscarriages. No case of OHSS was encountered. On comparison of the results of these patients (fresh cycles; n=7) with those of matched controls, there were no significant differences in terms of retrieved mature oocytes, implantation rates, or clinical pregnancy rates (p>0.05). These findings suggest that low-dose GnRH agonist triggering has similar efficacy as standard doses in terms of retrieved mature oocytes and clinical pregnancy rates in in vitro fertilization cycles.

  9. Does the use of gonadotropin-releasing hormone antagonists in natural IVF cycles for poor responder patients cause more harm than benefit?

    Aksoy, Senai; Yakin, Kayhan; Seyhan, Ayse; Oktem, Ozgur; Alatas, Cengiz; Ata, Baris; Urman, Bulent


    Poor ovarian response to controlled ovarian stimulation (COS) is one of the most critical factors that substantially limits the success of assisted reproduction techniques (ARTs). Natural and modified natural cycle IVF are two options that could be considered as a last resort. Blocking gonadotropin-releasing hormone (GnRH) actions in the endometrium via GnRH receptor antagonism may have a negative impact on endometrial receptivity. We analysed IVF outcomes in 142 natural (n = 30) or modified natural (n = 112) IVF cycles performed in 82 women retrospectively. A significantly lower proportion of natural cycles reached follicular aspiration compared to modified natural cycles (56.7% vs. 85.7%, p numbers of IVF cycles ending in embryo transfer (26.7% vs. 44.6%) was not statistically significant between natural cycle and modified natural IVF cycles. Clinical pregnancy (6.7% vs. 7.1%) and live birth rates per initiated cycle (6.7% vs. 5.4%) were similar between the two groups. Notably, the implantation rate was slightly lower in modified natural cycles (16% vs. 25%, p > 0.05). There was a trend towards higher clinical pregnancy (25% vs. 16%) and live birth (25% vs. 12%) rates per embryo transfer in natural cycles compared to modified natural cycles, but the differences did not reach statistical significance.

  10. Gonadotropin-releasing hormone (GnRH) receptors of cattle aggregate on the surface of gonadotrophs and are increased by elevated GnRH concentrations.

    Kadokawa, Hiroya; Pandey, Kiran; Nahar, Asrafun; Nakamura, Urara; Rudolf, Faidiban O


    The presence of gonadotropin-releasing hormone (GnRH) receptors (GnRHRs) on gonadotrophs in the anterior pituitary (AP) is an important factor for reproduction control. However, little is known regarding GnRHR gene expression in gonadotrophs of cattle owing to the lack of an appropriate anti-GnRHR antibody. Therefore, an anti-GnRHR antibody for immunohistochemistry, flow cytometry, and immunocytochemistry assays was developed to characterize GnRHR gene expression in gonadotrophs. The anti-GnRHR antibody could suppress GnRH-induced LH secretion from cultured AP cells of cattle. The GnRHR, luteinizing hormone (LH), and follicle stimulating hormone (FSH) in the AP tissue was analyzed by fluorescence immunohistochemistry. The GnRHRs were aggregated on a limited area of the cell surface of gonadotrophs, possibly localized to lipid rafts. The LH secretion was stimulated with increasing amounts of GnRH; however, excessive concentrations (> 1 nM) resulted in a decrease in LH secretion. A novel method to purify gonadotrophs was developed using the anti-GnRHR antibody and fluorescence-activated cell sorting. Flow cytometric analysis using the anti-GnRHR antibody for cultured bovine AP cells, however, failed to support the hypothesis that GnRH induces GnRHR internalization and decreases GnRHR on the surface of GnRHR-positive AP cells. In contrast, immunocytochemistry using primary antibodies for cultured bovine AP cells showed that 10 nM (P < 0.05) and 100 nM (P < 0.01) GnRH, but not 0.01-1 nM GnRH, increased GnRHR in the cytoplasm of LH-positive cells. In conclusion, these data suggested that GnRHRs were aggregated on the surface of gonadotrophs and GnRHR inside gonadotrophs increased with elevated concentrations of GnRH.

  11. Clinical characteristics and follow-up of 5 young Chinese males with gonadotropin-releasing hormone deficiency caused by mutations in the KAL1 gene

    Juan Li


    Full Text Available Isolated gonadotropin-releasing hormone (GnRH deficiency (IGD pertains to a group of genetic disorders consisting of anosmic hypogonadotropic hypogonadism (Kallmann syndrome, KS and normosmic idiopathic hypogonadotropic hypogonadism (nIHH. KS is genetically heterogeneous. We hereby present 5 young male patients with GnRH deficiency caused by mutations in the KAL1 gene. Their ages ranged from 9 months to 16 years. They were referred to our department for an endocrine consultation for micropenis. Hormone assays showed low circulating gonadotropins and testosterone. Molecular studies revealed KAL1 mutations in all cases, three reported nonsense sequence variants in the KAL1 gene were detected in 4 patients, respectively (c.784C > T (p.Arg 262*, c.1267C > T (p.Arg423*, and c.1270C > T (p.Arg424*, and one patient harbored a novel hemizygous sequence variant [c.227G > A (p.Trp76*]. Only one patient presented short stature without growth hormone deficiency and anosmia. Another patient had bilateral eyelid ptosis, trichiasis, and refractive error. This is the first report on the co-occurrence of a KAL1 gene mutation and tent-like upper lip in four patients. All of our cases had normal olfactory bulbs and showed no renal agenesis, cleft lip/palate, and hearing impairment. These cases expand our knowledge of the phenotype associated with KAL1 sequence variations, although the precise mechanism by which KAL1 gene influences the development of this phenotype is still unknown.

  12. Evaluation of dual trigger with gonadotropin-releasing hormone agonist and human chorionic gonadotropin in improving oocyte maturity rates: A prospective randomized study

    Nalini Mahajan


    Full Text Available BACKGROUND: Mature oocytes are prerequisite for achieving the process of in vitro fertilization. Human chorionic gonadotropin (hCG is the standard trigger used for stimulating ovulation but is associated with ovarian hyperstimulation syndrome (OHSS. Gonadotropin-releasing hormone agonist trigger achieves oocyte maturation and lowers the incidence of OHSS, but it has limitations of higher pregnancy loss rate and miscarriage rates. Coadministration of both hormones is found to improve the pregnancy rates and the number of mature oocytes retrieved. We aimed to assess if the dual trigger is better than the conventional hCG in triggering oocyte maturation. METHODOLOGY: The study included 76 female patients aged 24–43 years who were randomly divided into two groups with 38 patients in each arm. The study included patients with antimullerian hormone (AMH 4 ng/ml and AFC/ovary >12 to avoid OHSS risk with hCG trigger. RESULTS: The study showed statistically insignificant differences between dual group versus hCG group in terms of the number of oocytes retrieved (10.0 ± 5.6 vs. 8.7 ± 5.0; P = 0.2816, the number of mature oocytes recovered (8.4 ± 5.0 vs. 7.2 ± 4.0; P = 0.2588, fertilization rate (5.9 ± 4.2 vs. 5.6 ± 3.3; P = 0.7390, and the number of usable embryos on day 3 (4.0 ± 3.0 vs. 4.0 ± 2.4; P = 0.8991. CONCLUSION: The dual trigger is equivalent to hCG in triggering oocyte maturation.

  13. Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

    Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.


    Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist.

  14. Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution.

    Pucarelli, Ida; Segni, Maria; Ortore, Massimiliano; Arcadi, Elena; Pasquino, Anna Maria


    Out of 35 girls with idiopathic central precocious puberty (CPP) treated with gonadotropin-releasing hormone agonist (GnRHa) (depot-triptorelin) at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 years whose growth velocity fell below the 25th percentile for chronological age (CA), 17 received growth hormone (GH) in addition at a dose of 0.3 mg/kg/week, s.c., 6 days per week, for 2-4 years. The other 18, matched for bone age (BA), CA and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, remained on GnRHa alone, and were used as a control group to evaluate GH efficacy. No patient was GH deficient. Both groups discontinued treatment at a comparable BA (mean +/- SD): BA 13.4 +/- 0.6 in GnRHa plus GH group vs 13.0 +/- 0.5 years in the GnRHa alone group. The 35 patients have reached adult height (i.e. growth during the preceding year was less than 1 cm, with a BA of over 15 years). Patients of the group treated with GH plus GnRHa showed an adult height (161.2 +/- 4.8 cm) significantly higher (p < 0.001) than pre-treatment predicted adult height (PAH) calculated according to tables either for accelerated girls (153.2 +/- 5.0 cm) or for average girls (148.6 +/- 4.3 cm). The adult height of the GnRH alone treated group (156.6 +/- 5.7) was not significantly higher than pre-treatment PAH if calculated on Bayley and Pinneau tables for accelerated girls (153.9 +/- 3.8 cm), whilst it remained significantly higher if calculated on tables for average girls (149.6 +/- 4.0 cm) (p < 0.001). The gain between pre-treatment PAH and final height was 8.2 +/- 4.8 cm according to tables for accelerated girls and 12.7 +/- 4.8 cm according to tables for average girls in patients treated with GH plus GnRHa; while in patients treated with GnRH alone the gain calculated between pre-treatment PAH for accelerated girls was just 2.3 +/- 2.9 cm and 7.1 +/- 2.7 cm greater than pre-treatment PAH for average girls. The difference between the gain

  15. Pituitary binding and internalization of radioiodinated gonadotropin-releasing hormone agonist and antagonist ligands in vitro and in vivo

    Wynn, P.C.; Suarez-Quian, C.A.; Childs, G.V.; Catt, K.J.


    In rat pituitary gonadotrophs, the rates of binding and endocytosis of two GnRH superagonist analogs, (D-Ala6,Pro9-NEt)GnRH and (D-Lys6,Pro9-NEt)GnRH, were compared with those of the potent antagonist analog (N-acetyl-D-pCl-Phe1,2,D-Trp3,D-Lys6,D-Ala10)GnRH by quantitative electron microscopic autoradiography. In dispersed pituitary cells, the two agonist analogs showed similar binding kinetics and comparable degrees of sequestration, as measured by their resistance to dissociation by low pH buffer. However, quantification of silver grain localization suggested that cellular internalization of the (D-Ala6)GnRH agonist increased more rapidly than that of the (D-Lys6)GnRH analog. These discrepancies, and the finding that a larger amount of the specifically bound /sup 125/I-(D-Ala6)GnRH agonist was removed during glutaraldehyde fixation, indicated that the proportional internalization of this analog was over estimated by quantitative autoradiography owing to loss of cell surface-bound radioligand. We, therefore, employed radioiodinated D-Lys6-substituted analogs to analyze the receptor binding and cellular uptake of GnRH agonist and antagonist derivatives in vivo. After iv injection, a high proportion of the /sup 125/I-(D-Lys6)GnRH agonist was translocated into pituitary gonadotrophs within 60 min, whereas the D-Lys6 antagonist was predominantly associated with the plasma membrane during that time. Four hours after injection of the antagonist, an appreciable proportion of silver grains was associated with intracellular organelles, and this trend increased progressively at later time points. The relatively prolonged cellular processing of the GnRH antagonist is consistent with in vivo binding kinetics, and its slower internalization may reflect the basal rate of GnRH receptor turnover in the cell membrane.

  16. Effects of shortened photoperiod on gonadotropin-releasing hormone, gonadotropin, and vitellogenin gene expression associated with ovarian maturation in rainbow trout.

    Choi, Sungchang; Lee, Cheul Ho; Park, Woodong; Kim, Dae-Jung; Sohn, Young Chang


    Reproductive activities of salmonids are synchronized by changes in photoperiod, which control the endocrine system via the brain-pituitary-gonadal axis. Gonadotropin-releasing hormone (GnRH) in the brain regulates synthesis and release of the pituitary gonadotropins (GTHs; FSH and LH). FSH and LH in turn stimulate the production of sex steroids for oocyte growth and maturation-Inducing steroid hormones for oocyte maturation and ovulation, respectively, in female salmonids. To clarify effects of long-term photoperiod manipulations on the reproductive activity of salmonids from early recrudescence to ovulation, we Investigated the gene expression profiles of GnRH, GTHs, and vitellogenin (VTG), and plasma sex steroids in female rainbow trout (Oncorhynchus mykiss). In addition, the percentages of eyed embryos and hatched alevins were examined together with the number of ovulated eggs to evaluate the effects of photoperiod regimes on egg quality. During late summer, the mRNA levels of GnRHs, GTHalpha, and LHbeta, and the plasma level of a maturational steroid (17alpha,20beta-dihydroxy-4-pregnen-3-one; 17,20beta-P) were significantly elevated by a gradually shortened photoperiod under constant temperature, in accordance with accelerated sexual maturation. The percentages of eyed embryos and hatched alevins from fish ovulated in August were comparable to those of control fish observed in December. These results clearly indicate that syntheses of GnRHs, LH, VTG, and 17,20beta-P are effectively accelerated by a programmed long-short photoperiod regime in early recrudescent female rainbow trout, without a marked deterioration in egg quality.

  17. Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?

    Ren, Jianzhi; Sha, Aiguo; Han, Dongmei; Li, Ping; Geng, Jie; Ma, Chaihui


    To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET). Retrospective cohort study. University-affiliated hospital. Normogonadotropic women undergoing IVF. Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol. Live-birth rate per fresh ET. In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol. Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

    Busby, Ellen R.; Sherwood, Nancy M.


    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups. PMID:28346489

  19. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice.

    Busby, Ellen R; Sherwood, Nancy M


    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15-28 may account for the altered metabolism in the prepubertal female pups.

  20. Developmental programming: impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus.

    Mahoney, Megan M; Padmanabhan, Vasantha


    Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5mg/kg/day) from day 30 to 90 of gestation (term 147d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F(2alpha), just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female.

  1. Final Oocyte Maturation in Assisted Reproduction with Human Chorionic Gonadotropin and Gonadotropin-releasing Hormone agonist (Dual Trigger).

    Oliveira, Sofia Andrade de; Calsavara, Vinícius Fernando; Cortés, Gemma Castillón


    Final oocyte maturation with Human Chorionic Gonadotropin (hCG) and ovarian stimulation with Follicle Stimulation Hormone (FSH) combined with Gonadotrophin-releasing Hormone (GnRH) antagonist to block Luteinizing hormone (LH) surge is a standard procedure of in vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI). However, GnRH agonist has been replacing the use of hCG in certain situations, especially in patients at risk of Ovarian Hyperstimulation Syndrome (OHSS). Some studies have also shown advantages in the combined use of GnRH agonist concurrently with hCG in inducing final oocyte maturation, a treatment known as "Dual Trigger". In theory, this method combines the advantages of both induction regimens, and it has brought promising results. The objective of this study is to compare Dual Trigger with the use of hCG alone or the use of GnRH agonist alone. A systematic review of articles on Dual Trigger and a retrospective cohort study comparing the three methods of induction of final oocyte maturation have been conducted. It has been found that Dual Triggering for poor responder patients had a statistically significant increase in the number of retrieved oocytes, mature oocytes, and fertilized embryos in the positive beta hCG rate, implantation rate, and newborn/transferred embryo (TE) rate.

  2. Anterior Pituitary Leptin Expression Changes in Different Reproductive States: Stimulation, in vitro, by Gonadotropin Releasing Hormone (GnRH)

    Akhter, Noor; Johnson, Brandy W.; Crane, Christopher; Iruthayanathan, Mary; Zhou, Yi-Hong; Kudo, Akihiko; Childs, Gwen V.


    This study was designed to learn more about the changes in expression of rat anterior pituitary (AP) leptin during the estrous cycle. QRT-PCR assays of cycling rat AP leptin mRNA showed 2—fold increases from metestrus to diestrus followed by an 86% decrease on the morning of proestrus. Percentages of leptin cells increased in proestrus and pregnancy to 55–60% of AP cells. Dual labeling for leptin proteins and growth hormone (GH) or gonadotropins, showed that the rise in leptin protein-bearing...

  3. Comparing the Use of Uterine Artery Embolization to Gonadotropin-Releasing Hormone Agonists in Shrinking Fibroid Size: A Pilot Study in Kazakhstan

    Balkenzhe Imankulova


    Full Text Available Introduction: Uterine fibroids are the most common benign tumor in women in Kazakhstan. In the past two decades, endoscopic surgery has played an important role in the development of gynecologic surgery, particularly in the treatment of uterine fibroids. The goal of this paper is to evaluate whether uterine artery embolization (UAE or gonadotropin-releasing hormone agonists (GnRHa prior to myomectomy was more effective in decreasing fibroid size and improving surgical outcomes in a pilot study of women in Kazakhstan.Methods: This pilot investigation included 24 patients separated into 2 groups: medication group (pre-treatment with GnRHa – 13 patients and embolization group (pre-treatment with UAE – 11 patients. All patients had uterine fibroids, 3-10 cm in diameter, and were treated with myomectomy at the National Research Center for Maternal and Child Health, Astana, Kazakhstan. All patient data were obtained by a retrospective medical records review. Descriptive statistics were utilized to characterize participant demographics data. Independent t-tests were used to analyze continuous variables, and Chi-square and Fisher’s exact tests were used where appropriate for count data.Results: The group treated with GnRHa had an operating time of 40±10 minutes longer than the group treated with UAE, due to the peri-operative difficulties encountered by surgeons in detecting the layer between the myometrium and fibroid capsule. The group treated with UAE experienced better patient outcomes (less blood loss, less surgical time, and reduced use of anesthesia and was a technically easier surgery due to visible differences in uterine layers.Conclusions: Despite the fact that both treatments (GnRHa and UAE were effective for fibroid shrinking, embolization resulted in more optimal surgical time and improved patient outcomes. Results of this pilot study need to be confirmed in a randomized clinical trial, specifically focused on Kazakhstan and the

  4. Different gonadotropin releasing hormone agonist doses for the final oocyte maturation in high-responder patients undergoing in vitro fertilization/intra-cytoplasmic sperm injection

    Emre Goksan Pabuccu


    Full Text Available Context: Efficacy of gonadotropin releasing hormone agonists (GnRH-a for ovulation in high-responders. Aims: The aim of the current study is to compare the impact of different GnRH-a doses for the final oocyte maturation on cycle outcomes and ovarian hyperstimulation syndrome (OHSS rates in high-responder patients undergoing ovarian stimulation. Settings And Designs: Electronic medical records of a private in vitro fertilization center, a retrospective analysis. Subjects and Methods: A total of 77 high-responder cases were detected receiving GnRH-a. Group I consisted of 38 patients who received 1 mg of agonist and Group II consisted of 39 patients who received 2 mg of agonist. Statistical Analysis: In order to compare groups, Student′s t-test, Mann-Whitney U-test, Pearson′s Chi-square test or Fisher′s exact test were used where appropriate. A P < 0.05 was considered as statistically significant. Result: Number of retrieved oocytes (17.5 vs. 15.0, P = 0.510, implantation rates (46% vs. 55.1%, P = 0.419 and clinical pregnancy rates (42.1% vs. 38.5%, P = 0.744 were similar among groups. There were no mild or severe OHSS cases detected in Group I. Only 1 mild OHSS case was detected in Group II. Conclusion: A volume of 1 or 2 mg leuprolide acetate yields similar outcomes when used for the final oocyte maturation in high-responder patients.

  5. Phosphorylation substrates for protein kinase C in intact pituitary cells: characterization of a receptor-mediated event using novel gonadotropin-releasing hormone analogues

    Strulovici, B.; Tahilramani, R.; Nestor, J.J. Jr.


    The involvement of protein kinase C in the signal transduction of gonadotropin-releasing hormone (GnRH) action was investigated with a GnRH superagonist, partial agonists, and antagonists in intact rat pituitary cells. Exposure of /sup 32/P-labeled cells to GnRH or to the superagonist (D-Nal(2)/sup 6/)GnRH induced the enhanced phosphorylation of 42-, 34-, 11-, and 10-kDa proteins and the dephosphorylation of a 15-kDa protein as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography. This effect was blocked in a dose-dependent manner by potent GnRG antagonists. Downregulation of protein kinase C by prolonged incubation of the pituitary cells with high concentrations of active phorbol esters abolished protein kinase C activity and also prevented the phosphorylation induced by GnRN, or (D-Nal(2)/sup 6/)GnRH. The same effect was obtained by preincubating the cells with the protein kinase C inhibitor H-7. In this study the authors identify for the first time physiological substrates for protein kinase C in intact pituitary cells. They demonstrate a close quantitative correlation between the extent of translocation of protein kinase C, levels of phosphorylation of specific substrates in the intact cells, and the biological activity of the GnRH analogues with varying affinity for the GnRH receptor. These data strengthen the contention that the physiological effects of GnRH are primarily mediated via the phosphatidylinositol/Ca/sup 2 +/ signal transfer system and represent a first step toward defining the physiological substrates of protein kinase C and their role in the cascade of events that starts upon binding of GnRH to its receptor.

  6. Extracellular signal-regulated kinase mediates gonadotropin subunit gene expression and LH release responses to endogenous gonadotropin-releasing hormones in goldfish.

    Klausen, Christian; Booth, Morgan; Habibi, Hamid R; Chang, John P


    The possible involvement of extracellular signal-regulated kinase (ERK) in mediating the stimulatory actions of two endogenous goldfish gonadotropin-releasing hormones (salmon (s)GnRH and chicken (c)GnRH-II) on gonadotropin synthesis and secretion was examined. Western blot analysis revealed the presence of ERK and phosphorylated (p)ERK in goldfish brain, pituitary, liver, ovary, testis and muscle tissue extracts, as well as extracts of dispersed goldfish pituitary cells and HeLa cells. Interestingly, a third ERK-like immunoreactive band of higher molecular mass was detected in goldfish tissue and pituitary cell extracts in addition to the ERK1-p44- and ERK2-p42-like immunoreactive bands. Incubation of primary cultures of goldfish pituitary cells with either a PKC-activating 4beta-phorbol ester (TPA) or a synthetic diacylglycerol, but not a 4alpha-phorbol ester, elevated the ratio of pERK/total (t)ERK for all three ERK isoforms. The stimulatory effects of TPA were attenuated by the PKC inhibitor GF109203X and the MEK inhibitor PD98059. sGnRH and cGnRH-II also elevated the ratio of pERK/tERK for all three ERK isoforms, in a time-, dose- and PD98059-dependent manner. In addition, treatment with PD98059 reduced the sGnRH-, cGnRH-II- and TPA-induced increases in gonadotropin subunit mRNA levels in Northern blot studies and sGnRH- and cGnRH-II-elicited LH release in cell column perifusion studies with goldfish pituitary cells. These results indicate that GnRH and PKC can activate ERK through MEK in goldfish pituitary cells. More importantly, the present study suggests that GnRH-induced gonadotropin subunit gene expression and LH release involve MEK/ERK signaling in goldfish.

  7. Effects of lamprey PQRFamide peptides on brain gonadotropin-releasing hormone concentrations and pituitary gonadotropin-β mRNA expression.

    Daukss, Dana; Gazda, Kristen; Kosugi, Takayoshi; Osugi, Tomohiro; Tsutsui, Kazuyoshi; Sower, Stacia A


    Within the RFamide peptide family, PQRFamide peptides that include neuropeptide FF and AF possess a C-terminal Pro-Gln-Arg-Phe-NH(2) motif. We previously identified PQRFamide peptides, lamprey PQRFa, PQRFa-related peptide (RP)-1 and -RP-2 by immunoaffinity purification in the brain of lamprey, one of the most ancient vertebrate species [13]. Lamprey PQRFamide peptide precursor mRNA was expressed in regions predicted to be involved in neuroendocrine regulation in the hypothalamus. However, the putative function(s) of lamprey PQRFamide peptides (PQRFa, PQRFa-RP-1 and PQRFa-RP-2) were not examined nor was the distribution of PQRFamide peptides examined in other tissues besides the brain. The objective of this study was to determine tissue distribution of lamprey PQRFamide peptide precursor mRNA, and to examine the effects of PQRFamide peptides on brain gonadotropin-releasing hormone (GnRH)-I, -II, and -III protein concentrations, and pituitary gonadotropin (GTH)-β mRNA expression in adult lampreys. Lamprey PQRFamide peptide precursor mRNA was expressed in the eye and the brain. Lamprey PQRFa at 100 μg/kg increased brain concentrations of lamprey GnRH-II compared with controls. PQRFa, PQRFa-RP-1 and PQRFa-RP-2 did not significantly change brain protein concentrations of either lamprey GnRH-I, -III, or lamprey GTH-β mRNA expression in the pituitary. These data suggest that one of the PQRFamide peptides may act as a neuroregulator of at least the lamprey GnRH-II system in adult female lamprey.

  8. Noradrenaline modulates the presence of gonadotropin-releasing hormone in ovary. The importance of its interrelation on the ovarian steroidogenesis and apoptosis on dioestrus II in rat.

    Bronzi, Cynthia D; Orozco, Adriana S Vega; Rodriguez, Diego; Rastrilla, Ana María; Sosa, Zulema Y; Casais, Marilina


    The aim of this work was to investigate if noradrenaline (NA), added in the coeliac ganglion -superior ovarian nerve- ovary system (CG-SON-O) and in ovary incubation, modifies the release of ovarian progesterone (P4), gonadotropin-releasing hormone (GnRH) and oestradiol (E2), and the expression of 3β-HSD and 20α-HSD and proapoptotic bax and antiapoptotic bcl-2 on dioestrus II in the rat. The CG-SON-O system and the ovary were removed and placed in one cuvette containing Krebs-Ringer solution (control groups), and NA was added to the ganglion compartment in the ex vivo system and in the ovary compartment in the ovary incubation (experimental groups). P4, GnRH and E2 were measured by RIA, and gene expression was measured by RT-PCR. In the ex-vivo system, the release of ovarian P4 and GnRH and the expression of 3β-HSD and bax decreased; E2 and bcl-2 increased, and the bax/bcl-2 ratio decreased. However, in the ovary incubation, P4, GnRH, the expression of 3β-HSD and bax increased; E2, the expression of 20α-HSD and bcl-2 decreased while the bax/bcl-2 ratio increased, thus favoring apoptosis. The peripheral nervous system protected the ovary from the apoptotic mechanisms while in the ovary incubation the effect was reverted. Our results indicate that NA regulates ovarian steroidogenesis and apoptosis by modulating GnRH release from the coeliac ganglion and ovary, being NA a possible generator of a GnRH-gonadotropins axis in the ovary. This work is expected to contribute with new evidence of the clinical importance of catecholamines and GnRH in therapy and prevention of ovarian pathologies.

  9. Gonadotropin-releasing hormone for preservation of ovarian function during chemotherapy in lymphoma patients of reproductive age: a summary based on 434 patients.

    Yaoyao Zhang

    Full Text Available BACKGROUND: Gonadotropin-releasing hormone agonists (GnRHa might play a role in preserving ovarian function in lymphoma patients by inhibiting chemotherapy-induced ovarian follicular damage. However, studies of its clinical efficacy have reported conflicting results. METHOD: We conducted a meta-analysis to determine the effect of the preservation of ovarian function by administering GnRHa in young patients with lymphoma undergoing chemotherapy. Seven studies were identified that met inclusion criteria and comprised 434 patients assigned to GnRHa combined chemotherapy or chemotherapy alone. RESULTS: The incidence of women with premature ovarian failure (POF demonstrated a statistically significant difference in favor of the use of GnRHa (OR=0.32, 95% CI 0.13-0.77. In addition, the final level of FSH in the GnRH group was significantly lower than control group. (MD= -11.73, 95% CI,-22.25- -1.20, and the final level of AMH in the GnRH group was significantly higher than control group (MD=0.80; 95% CI, 0.61-0.98. However, there was no statistically significant difference between treatment and the control groups in the incidence of a spontaneous pregnancy (OR=1.11; 95% CI, 0.55-2.26. CONCLUSION: This meta-analysis suggests that GnRHa may be effective in protecting ovarian function during chemotherapy in lymphoma patients. More well-designed prospective studies are needed to carry out for further understanding of this topic.

  10. Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial.

    Anita Kåss

    Full Text Available Gonadotropin-releasing hormone (GnRH and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels.We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53, i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99. Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5 or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed.The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP, improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010. By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049, DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012, and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026. Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively compared with placebo by day 15. Adverse event rates were similar between groups.GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in NCT00667758.

  11. Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices.

    Glanowska, Katarzyna M; Venton, B Jill; Moenter, Suzanne M


    Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for the central regulation of fertility. There is no method allowing real-time GnRH detection in brain slices. We developed fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFME) to detect GnRH release and validated it using a biologically relevant system. FSCV parameters (holding potential, switching potential, and scan rate) were determined for stable GnRH detection in vitro, then optimized for GnRH detection in mouse brain slices. Placement of CFMEs in the median eminence (ME) near GnRH terminals allowed detection of both KCl-evoked and spontaneous GnRH release. GnRH release was also detected from GnRH fibers passing near GnRH soma and near fiber-fiber appositions in the preoptic area. No GnRH signal was detected from CFMEs in the ME of hpg mice, which lack GnRH, or in regions not containing GnRH neurons in wild-type mice; application of exogenous GnRH produced a signal similar to that observed for spontaneous/evoked endogenous GnRH release. Using an established mouse model that produces diurnal variations in GnRH neuron activity, we demonstrated corresponding changes in spontaneous GnRH release in the median eminence. These results validate FSCV to detect GnRH in brain slices and provide new information on the sites and amounts of GnRH release, providing insight into its neuromodulatory functions.

  12. Novel mechanism for gonadotropin-releasing hormone neuronal migration involving Gas6/Ark signaling to p38 mitogen-activated protein kinase.

    Allen, Melissa P; Linseman, Daniel A; Udo, Hiroshi; Xu, Mei; Schaack, Jerome B; Varnum, Brian; Kandel, Eric R; Heidenreich, Kim A; Wierman, Margaret E


    Gonadotropin-releasing hormone (GnRH) is the central regulator of the reproductive axis. Normal sexual maturation depends on the migration of GnRH neurons from the olfactory placode to the hypothalamus during development. Previously, we showed restricted expression of the membrane receptor adhesion-related kinase (Ark) in immortalized cell lines derived from migratory but not postmigratory GnRH neurons. In addition, Ark and GnRH transcripts were detected along the GnRH neuron migratory route in the E13 mouse cribriform plate. In the present study, we examined the role of Ark and its ligand, Gas6 (encoded by growth arrest-specific gene 6), in GnRH neuron migration. Gas6 stimulated lamellipodial extension, membrane ruffling, and chemotaxis of immortalized NLT GnRH neuronal cells via the Ark receptor. Gas6/Ark signaling promoted activation of the Rho family GTPase Rac, and adenoviral-mediated expression of dominant negative N17Rac abolished Gas6/Ark-induced actin cytoskeletal reorganization and migration of GnRH neuronal cells. In addition, p38 MAPK was activated downstream of Ark and Rac, and inhibition of p38 MAPK with either SB203580 or adenoviral dominant negative p38alpha also blocked Gas6/Ark-mediated migration. Finally, downstream of Rac and p38 mitogen-activated protein kinase (MAPK), Gas6/Ark signaling promoted activation of MAPK-activated protein kinase 2 and induced phosphorylation of HSP25, a known regulator of cortical actin remodeling. The data are the first to demonstrate a migratory signaling pathway downstream of Ark/Axl family receptors and suggest a previously unidentified role for p38 MAPK in neuronal migration. Furthermore, these studies support a potential role for Ark in the regulation of GnRH neuronal migration.

  13. Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide.

    Pérez Sirkin, Daniela I; Lafont, Anne-Gaëlle; Kamech, Nédia; Somoza, Gustavo M; Vissio, Paula G; Dufour, Sylvie


    GnRH-associated peptide (GAP) is the C-terminal portion of the gonadotropin-releasing hormone (GnRH) preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D) structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH), despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH) structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation.

  14. Bone mineral density and body composition in girls with idiopathic central precocious puberty before and after treatment with a gonadotropin-releasing hormone agonist

    Sandra B. Alessandri


    Full Text Available OBJECTIVES: Idiopathic central precocious puberty and its postponement with a (gonadotropin-releasing hormone GnRH agonist are complex conditions, the final effects of which on bone mass are difficult to define. We evaluated bone mass, body composition, and bone remodeling in two groups of girls with idiopathic central precocious puberty, namely one group that was assessed at diagnosis and a second group that was assessed three years after GnRH agonist treatment. METHODS: The precocious puberty diagnosis and precocious puberty treatment groups consisted of 12 girls matched for age and weight to corresponding control groups of 12 (CD and 14 (CT girls, respectively. Bone mineral density and body composition were assessed by dual X-ray absorptiometry. Lumbar spine bone mineral density was estimated after correction for bone age and the mathematical calculation of volumetric bone mineral density. CONEP: CAAE-0311.0.004.000-06. RESULTS: Lumbar spine bone mineral density was slightly increased in individuals diagnosed with precocious puberty compared with controls; however, after correction for bone age, this tendency disappeared (CD = -0.74 + 0.9 vs. precocious puberty diagnosis = -1.73 + 1.2. The bone mineral density values of girls in the precocious puberty treatment group did not differ from those observed in the CT group. CONCLUSION: There is an increase in bone mineral density in girls diagnosed with idiopathic central precocious puberty. Our data indicate that the increase in bone mineral density in girls with idiopathic central precocious puberty is insufficient to compensate for the marked advancement in bone age observed at diagnosis. GnRH agonist treatment seems to have no detrimental effect on bone mineral density.

  15. Voltage-gated potassium currents are targets of diurnal changes in estradiol feedback regulation and kisspeptin action on gonadotropin-releasing hormone neurons in mice.

    Pielecka-Fortuna, Justyna; DeFazio, R Anthony; Moenter, Suzanne M


    Estradiol has both negative and positive feedback actions upon gonadotropin-releasing hormone (GnRH) release; the latter actions trigger the preovulatory GnRH surge. Although neurobiological mechanisms of the transitions between feedback modes are becoming better understood, the roles of voltage-gated potassium currents, major contributors to neuronal excitability, are unknown. Estradiol alters two components of potassium currents in these cells: a transient current, I(A), and a sustained current, I(K). Kisspeptin is a potential mediator between estradiol and GnRH neurons and can act directly on GnRH neurons. We examined how estradiol, time of day, and kisspeptin interact to regulate these conductances in a mouse model exhibiting daily switches between estradiol negative (morning) and positive feedback (evening). Whole-cell voltage clamp recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice and from OVX mice treated with estradiol (OVX+E). There were no diurnal changes in either I(A) or I(K) in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX+E mice, I(A) and I(K) were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased I(A) in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced I(A) regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized I(A) activation. These findings extend our understanding of both the neurobiological mechanisms of estradiol negative vs. positive regulation of GnRH neurons and of kisspeptin action on these cells.

  16. Radiation inactivation (target size analysis) of the gonadotropin-releasing hormone receptor: evidence for a high molecular weight complex

    Conn, P.M.; Venter, J.C.


    In the present study we used radiation inactivation (target size analysis) to measure the functional mol wt of the GnRH receptor while it is still a component of the plasma membrane. This technique is based on the observation that an inverse relationship exists between the dose-dependent inactivation of a macromolecule by ionizing radiation and the size of that macromolecule. This method demonstrates a mol wt of 136,346 +/- 8120 for the GnRH receptor. This estimate is approximately twice that obtained (60,000) by photoaffinity labeling with a radioactive GnRH analog followed by electrophoresis under denaturing conditions and, accordingly, presents the possibility that the functional receptor consists of a high mol wt complex in its native state. The present studies indicate that the GnRH receptor is either a single weight class of protein or several closely related weight classes, such as might occur due to protein glycosylation.

  17. Biological characterization of a novel and potent gonadotropin releasing hormone (GnRH) antagonist LXT-101

    Xiao-liCHI; Wen-xiaZHOU; Jun-pingCHENG; Yong-xiangZHANG; Ke-liangLIU


    AIM The biological characterization of LXT-101 was investigated in vivo using intact male rats and nude mice bearing xenografts of LNCaP prostate cancer. The effect of LXT-101 on the proliferation of androgen -sensitive prostate cancer cell LNCaP and androgen-insensitive DU145 and PC-3M in vitro was also determined. METHODS Rats were injected subcutaneously with LXT-101 while control animals received only vehicle (5% mannitol). Blood samples were collected at different time after adminis-tration of LXT-101. The androgen-dependent LNCaP prostate cancer cells were grown, mixed with Matrigel and injected subcutaneously into nude mice. Experimental group received LXT-101 injectionfor up to 4 weeks. At the end point, blood samples were drawn and the excised tumors and sex organswere weighted. The serum testosterone was determined by specific immunochemiluminescence assay using kits produced by Beckman-Counter Co. The mRNA expressions of the genes of hormone receptor related to the gonadal axis were investigated by real-time RT-PCR technique. Cell viability was determined by MTT method.

  18. Gonadotropin-releasing hormone stimulates prolactin release from lactotrophs in photoperiodic species through a gonadotropin-independent mechanism.

    Henderson, Helen L; Hodson, David J; Gregory, Susan J; Townsend, Julie; Tortonese, Domingo J


    Previous studies have provided evidence for a paracrine interaction between pituitary gonadotrophs and lactotrophs. Here, we show that GnRH is able to stimulate prolactin (PRL) release in ovine primary pituitary cultures. This effect was observed during the breeding season (BS), but not during the nonbreeding season (NBS), and was abolished by the application of bromocriptine, a specific dopamine agonist. Interestingly, GnRH gained the ability to stimulate PRL release in NBS cultures following treatment with bromocriptine. In contrast, thyrotropin-releasing hormone, a potent secretagogue of PRL, stimulated PRL release during both the BS and NBS and significantly enhanced the PRL response to GnRH during the BS. These results provide evidence for a photoperiodically modulated functional interaction between the GnRH/gonadotropic and prolactin axes in the pituitary gland of a short day breeder. Moreover, the stimulation of PRL release by GnRH was shown not to be mediated by the gonadotropins, since immunocytochemical, Western blotting, and PCR studies failed to detect pituitary LH or FSH receptor protein and mRNA expressions. Similarly, no gonadotropin receptor expression was observed in the pituitary gland of the horse, a long day breeder. In contrast, S100 protein, a marker of folliculostellate cells, which are known to participate in paracrine mechanisms within this tissue, was detected throughout the pituitaries of both these seasonal breeders. Therefore, an alternative gonadotroph secretory product, a direct effect of GnRH on the lactotroph, or another cell type, such as the folliculostellate cell, may be involved in the PRL response to GnRH in these species.

  19. Potential of a gonadotropin-releasing hormone vaccine to suppress musth in captive male Asian elephants (Elephas maximus).

    Somgird, Chaleamchat; Homkong, Pongpon; Sripiboon, Supaphen; Brown, Janine L; Stout, Tom A E; Colenbrander, Ben; Mahasawangkul, Sittidet; Thitaram, Chatchote


    Musth in adult bull elephants is a period of increased androgen concentrations ranging from a few weeks to several months. For captive elephant bull management, musth presents a serious challenge because of the aggressive behavior of musth bulls toward people and other elephants. Commercially available GnRH vaccines have been shown to suppress testicular function by interrupting the hypothalamo-pituitary-gonadal (HPG) axis in many species. The aim of this study was to test the efficacy of a GnRH vaccine in elephant bulls for suppressing the HPG axis and mitigating musth-related aggressive behavior. Five adult Asian elephant bulls (22-55 years old) were immunized with a GnRH vaccine starting with an initial injection 2-4 months before the predicted musth period, and followed by three boosters at approximately 4-week intervals. Blood samples were collected twice weekly for hormone and antibody titer analysis. An increase in GnRH antibody titers was observed in all bulls after the second or third booster, and titers remained elevated for 2-3 months after the final booster. Musth was attenuated and shortened in three bulls and postponed completely in two. We conclude that GnRH vaccination is capable of suppressing symptoms of musth in adult bull elephants. With appropriate timing, GnRH vaccination could be used to control or manage musth and aggressive behavior in captive elephant bulls. However, more work is needed to identify an optimal dose, booster interval, and vaccination schedule for complete suppression of testicular steroidogenesis.

  20. Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells.

    Choi, Jung-Hye; Choi, Kyung-Chul; Auersperg, Nelly; Leung, Peter C K


    Although gonadotropin-releasing hormone (GnRH) has been shown to play a role as an autocrine/ paracrine regulator of cell growth in ovarian surface epithelium and ovarian cancer, the factors which regulate the expression of GnRH and its receptor in these cells are not well characterized. In the present study, we employed real-time PCR to determine the potential regulatory effect of gonadotropins on the expression levels of GnRH I (the mammalian GnRH), GnRH II (a second form of GnRH) and their common receptor (GnRHR) in immortalized ovarian surface epithelial (IOSE-80 and IOSE-80PC) cells and ovarian cancer cell lines (A2780, BG-1, CaOV-3, OVCAR-3 and SKOV-3). The cells were treated with increasing concentrations (100 and 1000 ng/ml) of recombinant follicle-stimulating hormone (FSH) or luteinizing hormone (LH) for 24 h. Treatment with FSH or LH reduced GnRH II mRNA levels in both IOSE cell lines and in three out of five ovarian cancer cell lines (A2780, BG-1 and OVCAR-3). A significant decrease in GnRHR mRNA levels was observed in IOSE and ovarian cancer cells, except CaOV-3 cells, following treatment with FSH or LH. In contrast, treatment with either FSH or LH had no effect on GnRH I mRNA levels in these cells, suggesting that gonadotropins regulate the two forms of GnRH and its receptor differentially. In separate experiments, the effect of gonadotropins on the anti-proliferative action of GnRH I and GnRH II agonists in IOSE-80, OVCAR-3 and SKOV-3 cells was investigated. The cells were pretreated with FSH or LH (100 ng/ml) for 24 h after which they were treated with either GnRH I or GnRH II (100 ng/ml) for 2 days, and cell growth was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. Pretreatment of the cells with FSH or LH significantly reversed the growth inhibitory effect of GnRH I and GnRH II agonists in these cell types. These results provide the first demonstration of a potential interaction between gonadotropins and the

  1. Photoperiod-independent changes in immunoreactive brain gonadotropin-releasing hormone (GnRH) in a free-living, tropical bird.

    Moore, Ignacio T; Bentley, George E; Wotus, Cheryl; Wingfield, John C


    Timing of seasonal reproduction in high latitude vertebrates is generally regulated by photoperiodic cues. Increasing day length in the spring is associated with changes in the brain that are responsible for mediating reproductive activities. A primary example of this is the increased content of gonadotropin-releasing hormone (GnRH) in the preoptic area of the hypothalamus in birds as they enter the spring breeding season. Increased GnRH activity stimulates the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. These gonadotropins induce growth of the gonads and release of sex steroids which act on the brain to mediate reproductive behaviors. By contrast, seasonal breeding in the tropics can occur in the absence of significant changes in photoperiod. To our knowledge, no studies have investigated whether seasonal breeding in free-living tropical vertebrates is associated with seasonal changes in the GnRH system. We studied two populations of rufous-collared sparrows (Zonotrichia capensis) at the equator, separated by only 25 km, but with asynchronous reproductive phenologies associated with local climate and independent of photoperiodic cues. We collected brains and measured GnRH immunoreactivity (GnRH-ir) during each population's breeding and non-breeding periods. Breeding males had larger, but not more, GnRH-ir cells than non-breeding birds. The plasticity of the GnRH system was associated with local climate, such that the two populations exhibited asynchronous changes in GnRH-ir despite experiencing identical photoperiod conditions. Our results demonstrate that tropical birds can exhibit neural changes similar to those exhibited in higher latitude birds. However, these tropical populations appear to be using supplementary cues (e.g., rainfall, temperature, food availability) in a similar way to higher latitude species using an initial predictive cue (photoperiod). These results raise questions about the evolution of

  2. Utility of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a systematic review and meta-analysis

    Shen YW


    Full Text Available Yan-Wei Shen,1 Xiao-Man Zhang,1 Meng Lv,1 Ling Chen,1 Tian-Jie Qin,1 Fan Wang,1 Jiao Yang,1 Pei-Jun Liu,2 Jin Yang1 1Department of Medical Oncology, 2Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China Background: Premature ovarian failure and infertility following chemotherapy are major concerns for premenopausal women with breast cancer. A potential ovarian function preservation strategy is administration of gonadotropin-releasing hormone (GnRH agonists during adjuvant chemotherapy; however, studies of the clinical efficacy of GnRH agonists to protect chemotherapy-induced ovarian damage have shown mixed results. Objective: This meta-analysis study was designed to estimate the efficacy of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian damage in premenopausal women with breast cancer. Methods: Electronic literature databases (PubMed, EMBASE, MEDLINE, Cochrane Library databases searching, China National Knowledge Infrastructure, Web of Science, and the Wanfang Data were searched for relevant randomized controlled trials (RCTs published until September 2015. Only RCTs that examined the effect of GnRH agonists for chemotherapy-induced ovarian failure in premenopausal women with breast cancer were selected. The rate of spontaneous resumption of menses and spontaneous pregnancy were collected. All data were analyzed by RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark and Stata 12.0 (StataCorp, College Station, TX, USA. Results: Eleven RCTs with a total of 1,062 participants (GnRH agonists administered concurrently with chemotherapy, n=541; chemotherapy alone, n=521 were included in the meta-analysis. A significantly greater number of women treated with GnRH agonist experienced spontaneous resumption of menses after the adjuvant chemotherapy, yielding a pooled odds ratio of 2.57 (versus chemotherapy alone, 95

  3. A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1 Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

    Polly P Huang

    Full Text Available Gonadotropin-releasing hormone (GnRH, a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7 neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11 neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons.

  4. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio.

    Yali Zhao

    Full Text Available Kisspeptin1 (product of the Kiss1 gene is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while

  5. Expression of salmon gonadotropin-releasing hormone (GnRH) and chicken GnRH-II precursor messenger ribonucleic acids in the brain and ovary of goldfish.

    Lin, X W; Peter, R E


    The complementary DNAs (cDNA) encoding the [Trp7Leu8]gonadotropin-releasing hormone (salmon GnRH; sGnRH) precursor and the [His5Trp7Tyr8]GnRH (chicken GnRH-II; cGnRH-II) precursor of the goldfish brain were isolated and sequenced using reverse transcription and rapid amplification of cDNA ends (RACE). The sGnRH precursor cDNA consists of 540 bp, including an open reading frame of 282 bp, and the cGnRH-II precursor cDNA consists of 682 bp, including an open reading frame of 258 bp. The 94 amino acid-long goldfish sGnRH precursor and 86 amino acid-long goldfish cGnRH-II precursor have the same molecular architecture as GnRH precursors identified to date in other vertebrate species. Using two sets of primers designed to be sense and antisense to the goldfish brain sGnRH precursor cDNA sequence, reverse transcription-polymerase chain reaction (RT-PCR) amplification of total RNA from brain and ovary at gonadal recrudescent, mature ( = prespawning), and postovulatory stages resulted in two predicted sizes of PCR products. The intensities of staining signals of ethidium bromide were similar between brain and ovary samples. The same RT-PCRs were carried out with two sets of primers for cGnRH-II precursor cDNA, resulting in two PCR products of predicted size; however, the ethidium bromide staining signals are much weaker for products amplified from ovarian cDNA than that from brain cDNA. Restriction enzyme analysis verified the expected RT-PCR products. Sequence analysis of ovarian sGnRH precursor cDNA generated by RACE of total RNA from recrudescent ovarian tissue revealed the identical sequence to that of the brain sGnRH cDNA. Northern blot analysis detected a single mRNA transcript of approximately 650 bases for the sGnRH precursor in both the brain and ovary, and 750 bases for the cGnRH-II precursor in the brain. These results demonstrate that two forms of GnRH precursor (sGnRH and cGnRH-II) mRNA are expressed in goldfish brain tissue and that the sGnRH transcript and a

  6. Deletion of Vax1 from Gonadotropin-Releasing Hormone (GnRH) Neurons Abolishes GnRH Expression and Leads to Hypogonadism and Infertility.

    Hoffmann, Hanne M; Trang, Crystal; Gong, Ping; Kimura, Ikuo; Pandolfi, Erica C; Mellon, Pamela L


    Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates mammalian fertility. Herein we demonstrate a critical role for the homeodomain transcription factor ventral anterior homeobox 1 (VAX1) in GnRH neuron maturation and show that Vax1 deletion from GnRH neurons leads to complete infertility in males and females. Specifically, global Vax1 knock-out embryos had normal numbers of GnRH neurons at 13 d of gestation, but no GnRH staining was detected by embryonic day 17. To identify the role of VAX1 specifically in GnRH neuron development,Vax1(flox)mice were generated and lineage tracing performed in Vax1(flox/flox):GnRH(cre):RosaLacZ mice. This identified VAX1 as essential for maintaining expression of Gnrh1 The absence of GnRH staining in adult Vax1(flox/flox):GnRH(cre)mice led to delayed puberty, hypogonadism, and infertility. To address the mechanism by which VAX1 maintains Gnrh1 transcription, the capacity of VAX1 to regulate Gnrh1 transcription was evaluated in the GnRH cell lines GN11 and GT1-7. As determined by luciferase and electrophoretic mobility shift assays, we found VAX1 to be a direct activator of the GnRH promoter through binding to four ATTA sites in the GnRH enhancer (E1) and proximal promoter (P), and able to compete with the homeoprotein SIX6 for occupation of the identified ATTA sites in the GnRH promoter. We conclude that VAX1 is expressed in GnRH neurons where it is required for GnRH neuron expression of GnRH and maintenance of fertility in mice. Infertility classified as idiopathic hypogonadotropic hypogonadism (IHH) is characterized by delayed or absent sexual maturation and low sex steroid levels due to alterations in neuroendocrine control of the hypothalamic-pituitary-gonadal axis. The incidence of IHH is 1-10 cases per 100,000 births. Although extensive efforts have been invested in identifying genes giving rise to IHH, >50% of cases have unknown genetic origins

  7. Computer simulation of the free energy of peptides with the local states method: analogues of gonadotropin releasing hormone in the random coil and stable states.

    Meirovitch, H; Koerber, S C; Rivier, J E; Hagler, A T


    The Helmholtz free energy F (rather than the energy) is the correct criterion for stability; therefore, calculation of F is important for peptides and proteins that can populate a large number of metastable states. The local states (LS) method proposed by H. Meirovitch [(1977) Chemical Physics Letters, Vol. 45, p. 389] enables one to obtain upper and lower bounds of the conformational free energy, FB (b,l) and FA (b,l), respectively, from molecular dynamics (MD) or Monte Carlo samples. The correlation parameter b is the number of consecutive dihedral or valence angles along the chain that are taken into account explicitly. The continuum angles are approximated by a discretization parameter l; the larger are b and l, the better the approximations; while FA can be estimated efficiently, it is more difficult to estimate FB. The method is further developed here by applying it to MD trajectories of a relatively large molecule (188 atoms), the potent "Asp4-Dpr10" antagonist [cyclo(4/10)-(Ac-delta 3Pro1-D-pFPhe2-D-Trp3-Asp4-Tyr5-D-Nal6-Leu7-Arg8 -Pro9- Dpr10-NH2)] of gonadotropin releasing hormone (GnRH). The molecule was simulated in vacuo at T = 300 K in two conformational states, previously investigated [J. Rizo et al. Journal of the American Chemical Society, (1992) Vol. 114, p. 2860], which differ by the orientation of the N-terminal tail, above (tail up, TU) and below (tail down, TD) the cyclic heptapeptide ring. As in previous applications of the LS method, we have found the following: (1) While FA is a crude approximation for the correct F, results for the difference, delta FA = FA (TD)-FA (TU) converge rapidly to 5.6 (1) kcal/mole as the approximation is improved (i.e., as b and l are increased), which suggests that this is the correct value for delta F; therefore TD is more stable than TU. (The corresponding difference in entropy, T delta SA = 1.3(2) kcal/mole, is equal to the value obtained by the harmonic approximation.) (2) The lowest approximation, which has

  8. Influence of a gonadotropin-releasing hormone vaccine and dietary standardized ileal digestible lysine level on growth performance and carcass quality of grower-finisher pigs.

    Molist, F; Gerritsen, R; van der Aar, P; Prüst, H


    The aim of this study was to assess the effect of standardized ileal digestible (SID) Lys levels of the diet on the growth performance, carcass characteristics, and meat quality of entire males (EM), surgical castrates (SC), and males vaccinated with a gonadotropin-releasing hormone (GnRH) vaccine (GV). In total, 252 crossbred pigs were fed 6 different experimental diets consisting of 3 sexes (EM, SC, and GV pigs) and 2 dietary SID Lys levels (2008 CVB standard SID Lys recommendation [Std] or 15% extra SID Lys [+15]) according to a 3-phase feeding scheme (d 0 to 35, 35 to 70, and 70 to 105 of experiment) with 6 pens per treatment and 6 pigs per pen. To determine if dietary SID Lys could be reduced for GV males after the second vaccination, an additional dietary treatment was included (GV+15-Std). The GV males on the GV+15-Std were fed the diet with 15% extra SID Lys in the starter and grower phases and the standard SID Lys level in the finisher phase. First vaccination was administered to pigs at the start of the experiment (23.4 kg BW and 63.6 d of age), and the second vaccination occurred 6 wk before slaughter (77.2 kg BW and 126.6 d of age). Until the second vaccination, GV pigs showed a lower (P ≤ 0.05) ADFI than SC but similar to EM. After the second vaccination, GV pigs had an intermediate (P ≤ 0.05) G:F between EM and SC. The GV+15 pigs showed a better G:F (P ≤ 0.05) than GV pigs fed the GV+15-Std diet in the finisher phase. No differences in the growth rate of the pigs were observed. The SC had a greater (P ≤ 0.05) carcass weight and dressing percentage than EM and GV pigs. The GV-Std pigs had a lower (P ≤ 0.05) meat percentage and greater (P ≤ 0.05) backfat thickness than the GV+15 pigs. The GV pigs and SC fed the standard SID Lys diet had a greater (P ≤ 0.05) percentage of SFA in the subcutaneous fat than EM+15 pigs. On the other hand, SC showed the greatest (P ≤ 0.05) concentration of MUFA compared to EM and GV pigs. The SC and GV pigs

  9. Effect of gonadotropin-releasing hormone agonist therapy on body mass index and growth in girls with idiopathic central precocious puberty

    Ahmet Anik


    Full Text Available Objective: The study aimed to assess the effect of gonadotropin-releasing hormone (GnRH agonist therapy on body mass index (BMI and growth in girls diagnosed with idiopathic central precocious puberty (CPP. Materials and Methods: Hospital records of 32 girls with idiopathic CPP who have been receiving GnRH agonist therapy for at least 12 months were retrospectively reviewed and auxological, clinical and laboratory parameters of the patients were recorded. BMI, body mass index standard deviation score (BMI SDS for chronological age body mass index standard deviation score (CA-BMI SDS, BMI SDS for bone age body mass index standard deviation score (BA-BMI SDS, ratios of obesity and overweight were assessed before treatment and on the 12 th month of therapy in patients diagnosed with idiopathic CPP. Results: The study comprised of 32 girls diagnosed with idiopathic CPP. BMI values showed statistically significant increase in the 1 st year of treatment (19.16 ± 2.8 vs. 20.7 ± 3.4, P = 0.001. Despite a mild increase in CA-BMI SDS in the 1 st year of treatment versus before treatment, it was no statistically significant (1.0 ± 0.8 vs. 1.1 ± 0.9, P = 0.061. However, significant increase was observed in BA-BMI SDS in the 1 st year of treatment versus before treatment (0.8 ± 0.7 vs. 0.4 ± 0.8, P < 0.001. Before treatment, 37.5% (12/32 of the patients were overweight and 21.9% (5/32 were obese, whereas in the 1 st year, 34.4% (11/32 of the patients were overweight and 31.3% were obese (P = 0.001. Conclusion: Whilst 1/3 of the cases diagnosed with idiopathic CPP were overweight and obese at the time of diagnosis, GnRH agonist therapy caused statistically significant weight gain in patients diagnosed with CPP. Therefore, these patients should be closely monitored and weight control should be provided by diet and exercise programs in the course of treatment.

  10. Effects of kisspeptin1 on electrical activity of an extrahypothalamic population of gonadotropin-releasing hormone neurons in medaka (Oryzias latipes).

    Zhao, Yali; Wayne, Nancy L


    Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca(2+)/high Mg(2+) solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its

  11. The effects of gonadotropin-releasing hormone analogues on breast cancer and ovarian function protection%GnRH类似物在乳腺癌治疗中的应用和卵巢功能保护

    范嘉躜; 杨振宇; 曾涛


      促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)类似物治疗绝经前乳腺癌具有疗效好、停药后卵巢功能可恢复的特点,已取代手术和放疗成为治疗绝经前乳腺癌的一种主要治疗手段,现主要介绍GnRH类似物在乳腺癌内分泌治疗中的应用及其卵巢功能保护作用。%  The gonadotropin-releasing hormone (GnRH) analogues for the treatment of breast cancer has the characteristic of efficacy and menstruation recovery after treatment, which has replaced surgery and radiotherapy as a main treatment approach in the treatment of patients with premenopausal breast cancer. The effects of GnRH analogues on both the endocrine treatment of breast cancer and the protection of ovarian function are reviewed.

  12. Effect of gonadotropin-releasing hormone or prostaglandin F(2α)-based estrus synchronization programs for first or subsequent artificial insemination in lactating dairy cows.

    Bruno, R G S; Farias, A M; Hernández-Rivera, J A; Navarrette, A E; Hawkins, D E; Bilby, T R


    P/AI at 36 and 66 d after AI (GGPG=29.2 and 25.8, P7GPG=28.7 and 26.6, and P11GPG=31.9 and 30.2%) or pregnancy loss. Cows artificially inseminated upon ED had greater P/AI than TAI cows (ED=32.3 and TAI=25.1%). However, treatment did not affect P/AI for cows artificially inseminated upon ED at 36 and 66 d after AI (GGPG=29.6 and 27.3, P7GPG=29.4 and 28.1, and P11GPG=35.7 and 33.7%) or TAI (GGPG=29.1 and 25.3, P7GPG=25.0 and 22.1, and P11GPG=16.9 and 16.9%). Median days between NPD and AI was affected by treatment (GGPG=10 vs. P7GPG=4 and P11GPG=7 d). Prostaglandin-based programs increased ED and reduced interval to first AI and between AI. Gonadotropin-releasing hormone-based programs increased the proportion of TAI cows. Cows artificially inseminated upon ED had increased P/AI compared with TAI cows.

  13. Hormonal induction of spawning in 4 species of frogs by coinjection with a gonadotropin-releasing hormone agonist and a dopamine antagonist

    Trudeau, Vance L; Somoza, Gustavo M; Natale, Guillermo S; Pauli, Bruce; Wignall, Jacqui; Jackman, Paula; Doe, Ken; Schueler, Fredrick W


    It is well known that many anurans do not reproduce easily in captivity. Some methods are based on administration of mammalian hormones such as human chorionic gonadotropin, which are not effective in many frogs...

  14. Isolation of the gene and hypothalamic of cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat

    Adelman, J.P.; Mason, A.J.; Hayflick, J.S.; Seeburg, P.H.


    Cloned cDNAs encoding the precursor protein for gonadotropin-releasing hormone (Gn-RH) and prolactin release-inhibiting factor (PIF) were isolated from libraries derived from human and rat hypothalamic mRNA. Nucleotide sequence analyses predict precursor proteins of 92 amino acids for both species and show identity between the human placental and human hypothalamic precursor proteins. Whereas the Gn-RH peptide structure is completely conserved in human and rat, the PIF domain of the precursor displays 70% interspecies homology. Genomic analyses revealed the presence of a single Gn-RH-PIF gene in human and rat containing sequences corresponding to the cDNA distributed across four exons.

  15. Centrally Applied Somatostatin Inhibits the Estrogen-Induced Luteinizing Hormone Surge via Hypothalamic Gonadotropin-Releasing Hormone Cell Activation in Female Rats

    Vugt, van H.H.; Swarts, J.J.M.; Heijning, van de H.J.M.; Beek, van der E.M.


    Overexpression of growth hormone (GH) as well as GH-deficiency dramatically impairs reproductive function. Decreased reproductive function as a result of altered GH release is, at least partially, due to changes at the hypothalamic-pituitary level. We hypothesize that hypothalamic somatostatin (SOM)

  16. Antimüllerian hormone : Prediction of cumulative live birth in gonadotropin-releasing hormone antagonist treatment for in vitro fertilization

    Hamdine, Ouijdane; Eijkemans, Marinus J C; Lentjes, Eef G W; Torrance, Helen L.; Macklon, Nick S.; Fauser, Bart C J M; Broekmans, Frank J.


    Objective To assess the accuracy of antimüllerian hormone (AMH) in predicting cumulative live birth rate (CLBR) within 1 year after treatment initiation in GnRH antagonist treatment cycles for in vitro fertilization (IVF). Design Observational (retrospective) substudy as part of an ongoing

  17. Antimüllerian hormone: prediction of cumulative live birth in gonadotropin-releasing hormone antagonist treatment for in vitro fertilization.

    Hamdine, Ouijdane; Eijkemans, Marinus J C; Lentjes, Eef G W; Torrance, Helen L; Macklon, Nick S; Fauser, Bart C J M; Broekmans, Frank J


    To assess the accuracy of antimüllerian hormone (AMH) in predicting cumulative live birth rate (CLBR) within 1 year after treatment initiation in GnRH antagonist treatment cycles for in vitro fertilization (IVF). Observational (retrospective) substudy as part of an ongoing prospective cohort study. University medical center. A total of 487 patients scheduled for IVF/intracytoplasmic sperm injection (ICSI). Patients starting their first IVF/ICSI cycle with 150 or 225 IU recombinant FSH and GnRH antagonist cotreatment were included. Serum samples collected before the first IVF treatment were used to determine AMH. Treatment data after treatment initiation for a maximum of 1 year were recorded. Prediction of CLBR with the use of AMH. The model for predicting CLBR within 1 year included age at first treatment, AMH, type of infertility, and previous assisted reproductive technology treatment leading to live birth. The accuracy in discriminating between women who did or did not achieve a live birth was only 59%. AMH had intermediate added value in the prediction of CLBR as demonstrated by the net reclassification improvement (total 29.8). A nomogram based on age and AMH was developed by which a subgroup of patients could be identified with the poorest pregnancy prospects. The predictive accuracy of AMH for 1-year CLBR in GnRH antagonist treatment cycles was limited and did not yield much additional value on top of age. Withholding treatment based on predictors such as age and AMH, or a combination, remains problematic., NCT02309073. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Effect of feed restriction and initial body weight on growth performance, body composition, and hormones in male pigs immunized against gonadotropin-releasing factor.

    Moore, K L; Mullan, B P; Kim, J C; Payne, H G; Dunshea, F R


    Pigs immunized against gonadotropin-releasing factor (GnRF) have increased carcass fatness compared to entire males; however, the timing of this increase in fatness after the second immunization against GnRF has not been determined. An experiment was conducted to identify and compare the growth performance, body composition, and physiological changes in immunocastrated males (IC males) at different BW and feeding levels. A total of 64 pigs were used in a 2 × 2 × 2 factorial experiment with the treatments being 1) sex (entire males or IC males), 2) initial BW (45.9 kg [light] or 78.3 kg [heavy]), and 3) feeding regime (2.5 times maintenance [restricted] or ad libitum). The pigs were individually housed, and the diets were fed for 4 wk after the second immunization against GnRF until slaughter at either 68.4 kg BW (light) or 105.8 kg BW (heavy). Immunocastrated males on a restricted feed intake had a lower ADG compared to entire males from d 15 to 28 and d 0 to 28 ( 0.011 and 0.011, respectively). Fat deposition was not affected by sex from d 0 to 14, but from d 15 to 28 IC males deposited 45 g/d more fat than entire males ( = 0.025). Immunocastrated male pigs fed ad libitum deposited 87 g/d more fat from d 15 to 28 than entire males fed ad libitum ( = 0.036). However, there was no difference in fat deposition between IC males and entire males when feed intake was restricted from d 15 to 28. Plasma urea nitrogen levels were greater in IC males compared to entire males from d 7 after the second immunization against GnRF ( 0.05 for d 7, 10, 14, 21, and 28). Plasma concentrations of IGF-1 were lower for IC males compared to entire males on d 3, 7, 10, and 28 ( 0.05 for all days). The following conclusions were made: 1) when pigs are immunized at a light BW (50 kg) and/or are on a restricted feed intake, they have a reduced propensity to deposit fat; however, the restriction in feed intake adversely affects growth rate. 2) The majority of fat deposition for males

  19. Regulation of tonic gonadotropin release in prepubertal female hamsters

    Smith, S.G.; Matt, K.S.; Prestowitz, W.F.; Stetson, M.H.


    Basal serum gonadotropin levels were monitored weekly in female hamsters from birth to 10 weeks of age. Hamsters raised on three different photoperiods presented uniform pre- and postpubertal patterns of serum LH and FSH, suggesting that gonadotropin release in the young hamster occurs independently of ambient photoperiod. In all groups, serum LH levels increased gradually in animals up to 4 weeks of age, after which levels plateaued at 50--100 ng/ml. Serum FSH was markedly elevated in 2- and 3-week-old hamsters (800--1200 ng/ml), but remained at 200--400 ng/ml in all other groups. We next examined the change in the responsiveness of the pituitary to exogenous gonadotropin-releasing hormone (GnRH) challenge. Female hamsters 2 days of age failed to respond to any dose (0.025--1000 ng) of GnRH, while 10-day old females responded in typical dose-dependent fashion. GnRH-stimulated LH release first occurred in 6-day-old hamsters and was maximal by day 9, whereas FSH release first occurred on day 8 and was maximal by day 9. The prepubertal pattern of gonadotropin release can, in part, be explained on the basis of the development of pituitary GnRH sensitivity, which occurs independently of photoperiod.

  20. 促性腺激素释放激素(GnRH)结构及调控的研究进展%Research Progress on Structure and Regulation of Gonadotropin-releasing Hormone (GnRH)

    徐元青; 王建林; 邵宝平


    促性腺激素释放激素(GnRH)最初被认为是一种下丘脑神经肽,但是越来越多的研究发现该激素具有多重功能,如参与类固醇生成、细胞增殖、受精、粘连细胞外基质和细胞迁移等生理功能的调节,并在动物的生长发育、生殖行为、妊娠、分娩等生命活动中起着至关重要的作用。主要对GnRH的结构特点及其调控进行了综述。%Gonadotropin-releasing hormone (GnRH) is firstly taken as a kind of hypothalamic neuropeptide, but more and more researches show that GnRH has multiple functions, such as participating in the regulation of generation of steroids, cell proliferation, fertilization, adhesion of extracellular matrix, cell migration, etc., and also plays a crucial role in the growth, reproductive behavior, pregnancy and delivery of animals. The structure and regulation of GnRH were summarized.

  1. Comparison of gonadotropin-releasing hormone agonist with GnRH antagonist in polycystic ovary syndrome patients undergoing in vitro fertilization cycle: Retrospective analysis from a tertiary center and review of literature

    Neeta Singh


    Full Text Available Introduction: Polycystic ovary syndrome (PCOS is one of the most common infertility factor for which women are enrolled in in vitro fertilization (IVF technique. In the recent years, gonadotropin releasing hormone antagonist protocol has emerged as the protocol of choice for controlled ovarian hyperstimulation in these patients. Objectives: The objective of the present study is to compare conventional long agonist protocol with fixed antagonist protocol in PCOS patients undergoing IVF cycle. Materials and Methods: Retrospective analysis of 4 years data of a single center from northern India. Totally 81 patients who had long agonist protocol were compared with 36 patients with similar baseline characteristics who had antagonist protocol. Result: Total dose of gonadotropin required was significantly lower (P - 0.004 in the antagonist group. There was no significant difference in pregnancy rate or incidence of ovarian hyperstimulation syndrome between two groups. Cycle cancellation due to arrest of follicular growth was significantly higher in the antagonist group (P - 0.027. Conclusion: More randomized control trials and meta-analysis are required before replacing conventional long agonist protocol with antagonist protocol in patients with polycystic ovary syndrome.

  2. Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).

    Nakamura, Yasuhiro; Hattangady, Namita G; Ye, Ping; Satoh, Fumitoshi; Morimoto, Ryo; Ito-Saito, Takako; Sugawara, Akira; Ohba, Koji; Takahashi, Kazuhiro; Rainey, William E; Sasano, Hironobu


    Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Regulation of Insulin in Secretion and Activity of Gonadotropin-Releasing Hormone%胰岛素对促性腺激素释放激素分泌及活性的调控

    朱宇旌; 丁兰; 张勇; 王艳; 张宝生


    Insulin is a key hormone in regulating energy metabolism, whereas gonadotropin-releasing hormone (GnRH) is a key hormone in regulating animal reproduction, and an onset factor of empathema of animals. The shorten of time before empathema is important in livestock breeding. It has been widely reported that GnRH can be regulated by insulin in vivo, which controls empathema of animals. This paper mainly reviews the three factors (early growth response protein 1, extracellular regulated kinase and neuropeptide Y) associated with the regulation of insulin on the activity and function of GnRH and summarizes the regulation mechanism of insulin on GnRH in animal breeding.%胰岛素是动物体内能量代谢调控的重要激素,促性腺激素释放激素(GnRH)是动物体内调控繁殖的重要激素,是使动物发情的起始因素.促进家畜尽早进入发情期是现今畜牧业中的一个重要课题.大量研究报道了通过控制动物体内胰岛素水平可影响GnRH水平,从而调控动物发情.本文综述了胰岛素调节GnRH活性和功能过程中早期生长应答蛋白-1、胞外信号调节激酶和神经肽Y发挥的作用,对养殖生产实践中通过胰岛素调控实现GnRH分泌释放的机理作简要的总结.

  4. Elevation of plasma gonadotropin concentration in response to mammalian gonadotropin releasing hormone (GRH) treatment of the male brown trout as determined by radioimmunoassay

    Grim, L.W.; Cluett, D.M.


    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.

  5. Hindbrain lactate regulates preoptic gonadotropin-releasing hormone (GnRH) neuron GnRH-I protein but not AMPK responses to hypoglycemia in the steroid-primed ovariectomized female rat.

    Shrestha, P K; Briski, K P


    Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic end-product L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER-β), phosphoAMPK (pAMPK)] and inhibition (dopamine-beta-hydroxylase, GLUT3, MCT2) of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback-stimulated hypophysiotropic signaling to pituitary gonadotropes.

  6. In situ hybridization of gonadotropin releasing hormone receptor mRNA in rat pancreas%大鼠胰腺促性腺激素释放激素受体mRNA的原位杂交

    蒲若蕾; 黄威权; 吉秋合; 姚兵; 孙岚; 张荣庆; 王雷


    AIM To study whether gonadotropin releasing hormone receptor (GnRHR) mRNA exists in rat pancreas and its cellular localization. METHODS In situ hybridization with digoxigenin-labeled oligonucleotide probes was adopted. RESULTS Pancreatic endocrine islet cells, exocrine glandular cells and exocrine duct epithelial cells were all found to have GnRHR mRNA hybridization signals. The signals distributed in cytoplasm of all positive cells with negative nucli. CONCLUSION Both of the exocrine and endocrine cells of the pancrea can produce GnRH recepor. GnRH is also a kind of digestive hormone produced by pancrea and is responsible for modulating the exocrine and endocrine function.%目的 研究大鼠胰腺促性腺激素释放激素(GnRH)受体mRNA的存在及细胞定位. 方法 采用原位杂交组织化学法. 结果 胰脏的外分泌部腺上皮细胞、胰导管上皮细胞及内分泌部胰岛细胞内均可检测到较强的GnRH受体mRNA杂交信号. 杂交阳性信号物质均分布在胞质内,胞核呈阴性. 结论 大鼠胰脏内、外分泌部均能合成GnRH受体. GnRH也是一种消化激素,它由胰脏自身合成,又作用于胰脏,可能参与胰脏内、外分泌功能的调节.

  7. Relationship between polysialylated neural cell adhesion molecule and beta-endorphin- or gonadotropin releasing hormone-containing neurons during activation of the gonadotrope axis in short daylength in the ewe.

    Chalivoix, S; Malpaux, B; Dufourny, L


    Morphological plasticity has been demonstrated between breeding and anestrous seasons in the ewe hypothalamus, particularly for the gonadotropin-releasing hormone (GnRH) system. We sought to determine the impact of a photoperiodic transition, from long days (LD, 16 h light/24 h) to short days (SD; 8 h light/24 h), on the association between a marker of cerebral plasticity, the polysialylated form of neural cell adhesion molecule (PSA-NCAM), and two diencephalic populations: the GnRH and beta-endorphin (beta-END) neurons, the latter being potent inhibitors of GnRH neuronal activity. We also estimated the number of contacts on GnRH neurons after the passage to SD, using synaptophysin as a marker for synaptic buttons. Those parameters were evaluated in ovariectomized estradiol-replaced ewes using double immunocytochemistry and confocal microscopy at different times after the transition to SD: day 0 (D0), D30, D45, D60 and D112. Luteinizing hormone (LH) secretion was recorded throughout the experiment. High LH levels were observed only at D112. Significantly more PSA-NCAM was found in the GnRH neuron perimeters in the D112 group than in the other groups. This increase was not associated with any change in the number of synaptophysin-immunoreactive contacts on GnRH neurons. The beta-END peri-neuronal space was affected negatively by the transition to SD: the percentage of PSA-NCAM on beta-END neurons decreased between D45 and D112 in the posterior two thirds of the arcuate nucleus (ARC). These results suggest that photoperiod may reorganize cell interactions in different hypothalamic areas, ultimately reactivating GnRH neurons, in our model of ovariectomized-estradiol replaced ewes.

  8. Synaptic contacts between Gonadotropin-releasing hormone-containing fibres and neurons in the suprachiasmatic nucleus and perichiasmatic area: an anatomical substrate for feedback regulation?

    Beek, van der E.M.; Wiegant, V.M.; Oudheusden, van H.J.C.; Donk, van der H.A.; den Hurk, R.; Buijs, R.M.


    The suprachiasmatic nucleus (SCN) is critically involved in the generation and entrainment of circadian rhythms in mammalian species. Both the occurrence and the timing of the luteinizing hormone surge on the afternoon of proestrus in the female rodent are critically dependent on the integrity of th

  9. Does a nonclassical signaling mechanism underlie an increase of estradiol-mediated gonadotropin-releasing hormone receptor binding in ovine pituitary cells?

    Davis, Tracy L; Whitesell, Jennifer D; Cantlon, Jeremy D; Clay, Colin M; Nett, Terry M


    Estradiol-17beta (E2) is the major regulator of GnRH receptor (GnRHR) gene expression and number during the periovulatory period; however, the mechanisms underlying E2 regulation of the GNRHR gene remain undefined. Herein, we find that E2 conjugated to BSA (E2-BSA) mimics the stimulatory effect of E2 on GnRH binding in primary cultures of ovine pituitary cells. The time course for maximal GnRH analog binding was similar for both E2 and E2-BSA. The ability of E2 and E2-BSA to increase GnRH analog binding was blocked by the estrogen receptor (ER) antagonist ICI 182,780. Also, increased GnRH analog binding in response to E2 and the selective ESR1 agonist propylpyrazole triol was blocked by expression of a dominant-negative form of ESR1 (L540Q). Thus, membrane-associated ESR1 is the likely candidate for mediating E2 activation of the GNRHR gene. As cAMP response element binding protein (CREB) is an established target for E2 activation in gonadotrophs, we next explored a potential role for this protein as an intracellular mediator of the E2 signal. Consistent with this possibility, adenoviral-mediated expression of a dominant-negative form of CREB (A-CREB) completely abolished the ability of E2 to increase GnRH analog binding in primary cultures of ovine pituitary cells. Finally, the presence of membrane-associated E2 binding sites on ovine pituitary cells was demonstrated using a fluorescein isothiocyanate conjugate of E2-BSA. We suggest that E2 regulation of GnRHR number during the preovulatory period reflects a membrane site of action and may proceed through a nonclassical signaling mechanism, specifically a CREB-dependent pathway.

  10. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men.

    Herbst, Karen L; Coviello, Andrea D; Page, Stephanie; Amory, John K; Anawalt, Bradley D; Bremner, William J


    Acyline is a novel GnRH antagonist that reliably inhibits gonadotropins and testosterone (T) levels in men for 48 h after a single dose up to 75 microg/kg. In this study we examined gonadotropin and T levels in 28 healthy young men administered acyline as single doses of 150 or 300 microg/kg or serial injections of 75 microg/kg. A single 300 microg/kg dose of acyline suppressed gonadotropins and T to castrate levels for 15 d (baseline, 21.1 +/- 3.1; nadir, 1.95 +/- 0.4 nmol/liter; mean +/- sem; P gonadotropins for more than 20 d (nadir T, 1.06 +/- 0.17 nmol/liter; P hormonal male contraceptive or for treatment of hormonally dependent disease.

  11. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles.

    Lin, Ming-Huei; Wu, Frank Shao-Ying; Lee, Robert Kuo-Kuang; Li, Sheng-Hsiang; Lin, Shyr-Yeu; Hwu, Yuh-Ming


    To investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) can improve the live-birth rate for normal responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Retrospective cohort study. Infertility unit of a university-affiliated medical center. Normal responders to controlled ovarian hyperstimulation who were undergoing IVF-ICSI with a GnRH antagonist protocol. Standard dosage of hCG trigger (6,500 IU of recombinant hCG) versus dual trigger (0.2 mg of triptorelin and 6,500 IU of recombinant hCG). Live-birth, clinical pregnancy, and implantation rates per cycle. A total of 376 patients with 378 completed cycles with embryo transfer were enrolled (hCG trigger/control group: n = 187; dual trigger/study group: n = 191). The dual trigger group demonstrated statistically significantly higher implantation (29.6% vs. 18.4%), clinical pregnancy (50.7% vs. 40.1%), and live-birth (41.3% vs. 30.4%) rates as compared with the hCG trigger group. There was no statistically significant difference in terms of patient demographics, cycle parameters, or embryo quality. Dual trigger of final oocyte maturation with a GnRH-agonist and a standard dosage of hCG in normal responders statistically significantly improves implantation, clinical pregnancy, and live-birth rates in GnRH-antagonist IVF cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.


    Asda Laining


    Full Text Available Very low naturally mating rate of pond-reared tiger shrimp broodstock is probably due to the slow maturation of the male stock. The aim of this study was to evaluate the salmon gonadotrophin releasing hormone analoque (sGnRHa in stimulating the gonadal maturation of male stock of pond-reared tiger shrimp. The treatments were three dosages of sGnRHa at 0.1 (OV-1, 0.2 (OV-2, and 0.3 (OV-3 mL/kg of shrimp weight and control was eye stalk ablation (AB. The sGnRHa was administered via injection three times with one week interval. Male stocks with average initial body weight of 82.1 g were randomly distributed into four of 10 m3 concrete tanks, 26 males for each tank. Variables observed were performances of spermatophores and profiles of amino acid and fatty acid of muscle of the male stocks. After induction, number of male maturing indicated by spermatophores releasing from terminal ampullas was higher in shrimp induced with OV-1 (80.8% compared to control which was only 46.1%. Furthermore, shrimp treated OV-2 had the highest spermatophore weight of 0.16 g compared to control (0.11 g and other two groups. Amino acid profiles improved as the dose of sGnRHa increased up to 0.2 mL/kg from 61.23% for ablated male becoming 71.27% for OV-2. Total fatty acid also tended to improve by increasing the dose of hormone injection, however, the ablated male had higher total fatty acid content than that of OV-1. The present finding demonstrated that the dose of sGnRHa to stimulate the gonadal maturation of pond-reared male tiger shrimp could be applied at range between 0.1-0.2 mL/kg of shrimp weight.

  13. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  14. Effects of gonadotropin-releasing hormone administration or a controlled internal drug-releasing insert after timed artificial insemination on pregnancy rates of dairy cows

    Jeong, Jae Kwan; Choi, In Soo; Kang, Hyun Gu; Hur, Tai Young


    This study investigated the effects of gonadotrophin-releasing hormone (GnRH) administration (Experiment 1) and a controlled internal drug-releasing (CIDR) insert (Experiment 2) after timed artificial insemination (TAI) on the pregnancy rates of dairy cows. In Experiment 1, 569 dairy cows that underwent TAI (day 0) following short-term synchronization with prostaglandin F2α were randomly allocated into two groups: no further treatment (control, n = 307) or injection of 100 µg of gonadorelin on day 5 (GnRH, n = 262). In Experiment 2, 279 dairy cows that underwent TAI (day 0) following Ovsynch were randomly allocated into two groups: no further treatment (control, n = 140) or CIDR insert treatment from days 3.5 to 18 (CIDR, n = 139). The probability of pregnancy following TAI did not differ between the GnRH (34.4%) and control (31.6%, p > 0.05) groups. However, the probability of pregnancy following TAI was higher (odds ratio: 1.74, p < 0.05) in the CIDR group (51.1%) than in the control group (39.3%). Overall, CIDR insert treatment at days 3.5 to 18 increased pregnancy rates relative to non-treated controls, whereas a single GnRH administration on day 5 did not affect the pregnancy outcomes of dairy cows. PMID:27030200

  15. Progesterone treatment inhibits and dihydrotestosterone (DHT) treatment potentiates voltage-gated calcium currents in gonadotropin-releasing hormone (GnRH) neurons.

    Sun, Jianli; Moenter, Suzanne M


    GnRH neurons are central regulators of fertility, and their activity is modulated by steroid feedback. In normal females, GnRH secretion is regulated by estradiol and progesterone (P). Excess androgens present in hyperandrogenemic fertility disorders may disrupt communication of negative feedback signals from P and/or independently stimulate GnRH release. Voltage-gated calcium channels (VGCCs) are important in regulating excitability and hormone release. Estradiol alters VGCCs in a time-of-day-dependent manner. To further elucidate ovarian steroid modulation of GnRH neuron VGCCs, we studied the effects of dihydrotestosterone (DHT) and P. Adult mice were ovariectomized (OVX) or OVX and treated with implants containing DHT (OVXD), estradiol (OVXE), estradiol and DHT (OVXED), estradiol and P (OVXEP), or estradiol, DHT, and P (OVXEDP). Macroscopic calcium current (I(Ca)) was recorded in the morning or afternoon 8-12 d after surgery using whole-cell voltage-clamp. I(Ca) was increased in afternoon vs. morning in GnRH neurons from OVXE mice but this increase was abolished in cells from OVXEP mice. I(Ca) in cells from OVXD mice was increased regardless of time of day; there was no additional effect in OVXED mice. P reduced N-type and DHT potentiated N- and R-type VGCCs; P blocked the DHT potentiation of N-type-mediated current. These data suggest P and DHT have opposing actions on VGCCs in GnRH neurons, but in the presence of both steroids, P dominates. VGCCs are targets of ovarian steroid feedback modulation of GnRH neuron activity and, more specifically, a potential mechanism whereby androgens could activate GnRH neuronal function.

  16. Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

    Zhou, Huimei; Cao, Dongyan; Yang, Jiaxin; Shen, Keng; Lang, Jinghe


    The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is

  17. Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage: an experimental study with nu/nu athymic mice

    Qiong-yan LIN; Yi-feng WANG; Hui-nan WENG; Xiu-jie SHENG; Qing-ping JIANG; Zhi-ying YANG


    Background and objective:Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth.In this study,we determined whether administration of the GnRH agonist (GnRHa),triporelin,prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage.Methods:nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally.After two weeks,the mice were treated with saline (control),cisplatin,GnRHa,or cisplatin plus GnRHa for four weeks.At the end of the experimental protocol,blood,tumor,ovary,and uterine tissues were resected for hematoxylin and eosin (H&E) staining,immunohistochemical analyses of Ki67,nuclear factor-κB (NF-κB),and caspase-3,transmission electron microscopy of apoptosis,or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH).Results:Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity.Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05),but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05),while expressions of NF-κB and caspase-3 were reduced and induced,respectively,in cisplatin-treated mice and cisplatin plus GnRHa-treated mice.Apoptosis occurred in the GnRHa,cisplatin,and cisplatin plus GnRHa-treated mice,but not in control mice.Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05).Conclusions:Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin,but did not affect the anti-tumor activity of cisplatin.

  18. Immunoreactive gonadotropin-releasing hormone-like material in the brain and the pituitary gland during the periovulatory period in the brown trout (Salmo trutta L.): relationships with the plasma and pituitary gonadotropin.

    Breton, B; Motin, A; Billard, R; Kah, O; Geoffre, S; Precigoux, G


    In fish there are few data on the gonadotropin-releasing hormone (Gn-RH) neurosecretory activity, which could explain long- and short-term variations of the gonadotropin secretion. There is no biological species specificity between mammal and fish Gn-RH; although there is a structural difference, they are, on the contrary, characterized by a high immunological specificity which does not allow measurement of fish Gn-RH using radioimmunoassay for LH-RH. We have synthesized salmon Gn-RH according to the formula recently proposed by Sherwood (N. Sherwood, L. Eiden, M. Brownstein, J. Spies, J. Rivier, and W. Vale, 1983. Proc. Natl. Acad. Sci. USA 80, 2794-2798). Its activity has been tested by its ability to stimulate the gonadotropin hormone (GtH) secretion in vivo in testosterone-implanted juvenile rainbow trout, and for the recognition of synthesized Gn-RH (s-Gn-RH) perykaria by a specific antibody raised against the s-Gn-RH in regions of the brain described as containing LH-RH immunoreactive-like material. A radioimmunoassay has been developed for the salmon Gn-RH, and its specificity to measure trout Gn-RH has been tested. Using this assay, the brain and pituitary Gn-RH contents have been measured throughout the final phases of maturation and ovulation. Brain Gn-RH increases from the end of vitellogenesis (8.9 +/- 0.76 ng/brain) to ovulation (more than 15 ng/brain). Pituitary Gn-RH is lower (1.58 +/- 0.69 ng/pituitary) at the end of vitellogenesis and follows a similar profile as in the brain, except for a significant decrease just prior the beginning of oocyte maturation. The correlations between Gn-RH levels and GtH pituitary and plasma levels show that total brain Gn-RH is never correlated to the GtH, suggesting that the increase in the brain Gn-RH content is related to a Gn-RH system closely related to maturation and ovulation, which remains to be investigated. On the contrary, pituitary Gn-RH levels are well correlated with pituitary and plasma GtH levels

  19. Estrogen receptor beta and 2-arachydonoylglycerol mediate the suppressive effects of estradiol on frequency of postsynaptic currents in gonadotropin-releasing hormone neurons of metestrous mice: an acute slice electrophysiological study

    Flóra eBálint


    Full Text Available Gonadotropin-releasing hormone (GnRH neurons are controlled by 17β-estradiol (E2 contributing to the steroid feedback regulation of the reproductive axis. In rodents, E2 exerts a negative feedback effect upon GnRH neurons throughout the estrus-diestrus phase of the ovarian cycle. The present study was undertaken to reveal the role of estrogen receptor subtypes in the mediation of the E2 signal and elucidate the downstream molecular machinery of suppression. The effect of E2 administration at low physiological concentration (10 pM on GnRH neurons in acute brain slices obtained from metestrous GnRH-GFP mice was studied under paradigms of blocking or activating estrogen receptor subtypes and interfering with retrograde 2-arachydonoylglycerol (2-AG signaling. Whole-cell patch clamp recordings revealed that E2 significantly diminished the frequency of spontaneous postsynaptic currents (sPSCs in GnRH neurons (49. 62±7.6% which effect was abolished by application of the ERα/β blocker Faslodex (1 µM. Pretreatment of the brain slices with cannabinoid receptor type 1 (CB1 inverse agonist AM251 (1 µM and intracellularly applied endocannabinoid synthesis blocker THL (10 µM significantly attenuated the effect of E2 on the sPSCs. E2 remained effective in the presence of TTX indicating a direct action of E2 on GnRH cells. The ERβ specific agonist DPN (10 pM also significantly decreased the frequency of miniature postsynaptic currents (mPSCs in GnRH neurons. In addition, the suppressive effect of E2 was completely blocked by the selective ERβ antagonist PHTPP (1 µM indicating that ERβ is required for the observed rapid effect of the E2. In contrast, the ERα agonist PPT (10 pM or the membrane-associated G protein-coupled estrogen receptor (GPR30 agonist G1 (10 pM had no significant effect on the frequency of mPSCs in these neurons. AM251 and THL significantly abolished the effect of E2 whereas AM251 eliminated the action of DPN on the mPSCs. These

  20. Non-invasive assessment of the reproductive cycle in free-ranging female African elephants (Loxodonta africana treated with a gonadotropin-releasing hormone (GnRH vaccine for inducing anoestrus

    Benavides Valades Gabriela


    Full Text Available Abstract Background In southern Africa, various options to manage elephant populations are being considered. Immunocontraception is considered to be the most ethically acceptable and logistically feasible method for control of smaller and confined populations. In this regard, the use of gonadotropin-releasing hormone (GnRH vaccine has not been investigated in female elephants, although it has been reported to be safe and effective in several domestic and wildlife species. The aims of this study were to monitor the oestrous cycles of free-ranging African elephant cows using faecal progestagen metabolites and to evaluate the efficacy of a GnRH vaccine to induce anoestrus in treated cows. Methods Between May 2009 - June 2010, luteal activity of 12 elephant cows was monitored non-invasively using an enzyme immunoassay detecting faecal 5alpha-reduced pregnanes (faecal progestagen metabolites, FPM on a private game reserve in South Africa. No bulls of breeding age were present on the reserve prior to and for the duration of the study. After a 3-month control period, 8 randomly-selected females were treated twice with 600 micrograms of GnRH vaccine (Improvac®, Pfizer Animal Health, Sandton, South Africa 5-7 weeks apart. Four of these females had been treated previously with the porcine zona pellucida (pZP vaccine for four years (2004-2007. Results All 12 monitored females (8 treated and 4 controls showed signs of luteal activity as evidenced by FPM concentrations exceeding individual baseline values more than once. A total of 16 oestrous cycles could be identified in 8 cows with four of these within the 13 to 17 weeks range previously reported for captive African elephants. According to the FPM concentrations the GnRH vaccine was unable to induce anoestrus in the treated cows. Overall FPM levels in samples collected during the wet season (mean 4.03 micrograms/gram dry faeces were significantly higher (P Conclusions The GnRH vaccination protocol failed

  1. Efficacy and Safety Investigation of Kuntai Capsule for the Add-back Therapy of Gonadotropin Releasing Hormone Agonist Administration to Endometriosis Patients: A Randomized,Double-blind, Blank-and Tibolone-controlled Study

    Ji-Ming Chen; Hong-Yan Gao; Yi Ding; Xia Yuan; Qing Wang; Qin Li; Guo-Hua Jiang


    Background:As a Chinese Traditional Medicine product,Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women.But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment.The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule,on peri-menopausal symptoms in endometriosis (EMS) patients,with postoperative GnRH-a treatment.Methods:Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study,and were randomly divided into Kuntai group,Tibolone group,or blank Control group.The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection,while Tibolone 2.5 mg qd,po for 12 weeks in Tibolone group.There was no drug addition in Control group.Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score.Liver and renal functions,lipid profile,serum sex hormone levels and endometrial thickness were measured,and the frequency of adverse events in Kuntai and Tibolone groups was recorded.Results:(l) Before GnRH-a therapy,the baseline parameter results were comparable in the three groups (P > 0.05).(2) After GnRH-a therapy,KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05).At the 4th week after GnRH-a therapy,KMI and hot flash/sweating score results were as follows:Control group > Kuntai group > Tibolone group (P < 0.05); at the 8th and 12th week after GnRH-a therapy,KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05),and no significant difference was identified between Kuntai and Tibolone group (P > 0.05).(3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05).(4) The

  2. Distribution and Action of Gonadotropin-releasing Hormone in the Female Reproductive System%促性腺激素释放激素在女性生殖系统的分布与作用

    高江曼; 于洋; 乔杰


    促性腺激素释放激素(gonadotropin releasing hormone,GnRH)是下丘脑分泌的十肽激素,对生殖调控具有重要意义.人体中存在2种亚型,即GnRH-Ⅰ和GnRH-Ⅱ,以及2种相应的受体GnRHR-Ⅰ和GnRHR-Ⅱ. GnRH除了通过垂体性腺轴控制女性的发育、生殖功能外,同时还以自分泌和旁分泌的方式作用于垂体外组织,如乳腺、胎盘、卵巢、子宫内膜等.GnRH或许可作为乳腺癌的一种有效治疗和预防恶化的方法.GnRH类似物已经用于治疗许多激素相关的疾病,尤其是与子宫相关的疾病,如子宫内膜增生、子宫内膜癌、子宫内膜异位症(EMs),可降低子宫颈癌的风险等.胎盘自身可生成GnRH或GnRH样多肽物质,离体的胎盘组织体外培养表明,GnRH可显著增加胎盘组织人绒毛膜促性腺激素(hCG)的释放.局部的GnRHs对维持卵巢功能具有重要的作用;卵巢GnRHs参与正常和异常生殖组织的内分泌调控.%Gonadotrophin-releasing hormone (GnRH),a neuropeptide with 10 amino-acid,plays a critical role in the regulation of reproduction.There are 2 genome types of GnRH in human,GnRH-Ⅰ and GnRH-Ⅱ,and 2 types of receptor,GnRHR-Ⅰ and GnRHR-Ⅱ.They regulate the reproduction and maturity through the hypothalamicpituitary-gonadal axis,and also have the effect on some extrapituitary compartments by autocrine and/or paracrine,including the breast,placenta,ovary and endometrium.GnRH may be a valuable effective method of treatment and prevention of deterioration for breast cancer.GnRH analogues have been used to treat many hormones related diseases,especially uterine diseases,such as endometrial hyperplasia,endometrial cancer and endometriosis (EMs),as well as reduce the risk of cervical cancer.Placenta can generate GnRH or GnRH-like peptides.Studies of placental tissue in vitro indicate that GnRH can significantly increase the release of human chorionic gonadotropin (hCG) from placenta tissue.Local GnRHs not only plays an

  3. Immunological Recognition of Gonadotropin-releasing Hormone Receptor (GnRH-R) in the Mud Crab,Scylla paramamosain%拟穴青蟹GnRH-R的免疫识别

    陶永; 刘元婧; 叶海辉; 王桂忠; 李少菁


    Gonadotropin-releasing hormone (GnRH) and its receptor CGnRH-R) play an important role in the regulation of reproduction. To date,there has been little study on the GnRH and GnRH-R in invertebrates. In this study, with three GnRH-Rs of rabbit antibody against different species, including human,fruit fly and sea squirt, Western blotting and co-immunoprecipitation were applied to test the GnRH-R in mud crab.Scylla paramamosain. The common immunoreactive bands, with the molecular mass between 45 and 55 ku,appeared in the brain,thoracic ganglion,eyetalk and testes. Another band with 36 ku was found in the brain and thoracic ganglion. And in the testes,there was only a band with 28 ku using the antibody against human and fruit fly.while using rabbit antibody against sea squirt,there were bands with 28,36 and 30 ku. Two substance combined to GnRH-R were separated by co-immunoprecipitation.with the molecular mass of 38. 1 and 54. 0 ku, which were close to the mammal and non-mammal, respectively. This study shows that GnRH-R occurs in mud crab, which is helpful to further understanding of the regulation of reproduction in crustaceans.%促性腺激素释放激素(GnRH)及其受体(GnRH-R)对生殖具有重要的调控作用.迄今无脊椎动物GnRH及GnRH-R的研究尚少.本研究采用兔抗人GnRH-R、兔抗果蝇GnRH-R和兔抗海鞘GnRH-R的抗体,应用免疫印迹和免疫共沉淀技术对拟穴青蟹(Scylla paramamosain)GnRH-R进行了免疫识别,所得结果如下:1)经免疫印迹检测,拟穴青蟹脑、胸神经团、视神经节和精巢中共有的免疫阳性条带分子质量为45~55 ku.脑和胸神经团中另有一条36 ku条带;在精巢中,兔抗人GnRH-R和兔抗果蝇GnR H-R抗体只有一条28 ku条带,而兔抗海鞘GnRH-R抗体显示有28,36和30 ku的条带.2)利用免疫共沉淀技术,分离出与GnRH-R抗体相结合的两种物质,分子质量分别为38.1和54.0 ku,分别与哺乳动物和非哺乳动物GnRH-R的分子质量接近.该

  4. Glucagon-like peptide-1 excites firing and increases GABAergic miniature postsynaptic currents (mPSCs in gonadotropin-releasing hormone (GnRH neurons of the male mice via activation of nitric oxide (NO and suppression of endocannabinoid signaling pathways

    Imre Farkas


    Full Text Available Glucagon-like peptide-1 (GLP-1, a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9-39 (1 μM. Intracellular application of the G-protein inhibitor GDP-beta-S (2 mM impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO synthesis by L-NAME (100 μM or NPLA (1 μM or intracellular scavenging of NO by CPTIO (1 mM partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using CB1 inverse-agonist AM251 (1 μM. Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the TRPV1-antagonist AMG9810 (10 μM or the FAAH-inhibitor PF3845 (5 μM impeded the GLP-1-triggered endocannabinoid pathway indicating an anandamide-TRPV1-sensitive control of 2-AG production. Furthermore, GLP-1 immunoreactive axons innervated GnRH neurons in the hypothalamus suggesting that GLP-1 of both peripheral and neuronal sources can modulate GnRH neurons. RT-qPCR study confirmed the expression of GLP-1R and nNOS mRNAs in GnRH-GFP neurons. Immuno-electron microscopic analysis revealed the presence of neuronal nitric oxide synthase (nNOS protein in Gn

  5. Adult Height in Short Children Born SGA Treated with Growth Hormone and Gonadotropin Releasing Hormone Analog : Results of a Randomized, Dose-Response GH Trial

    Lem, Annemieke J.; van der Kaay, Danielle C. M.; de Ridder, Maria A. J.; Bakker-van Waarde, Willie M.; van der Hulst, Flip J. P. C. M.; Mulder, Jaap C.; Noordam, Cees; Odink, Roel J.; Oostdijk, Wilma; Schroor, Eelco J.; Sulkers, Eric J.; Westerlaken, Ciska; Hokken-Koelega, Anita C. S.


    Context: GH treatment is effective in improving height in short children born small for gestational age (SGA). GH is thought to have limited effect when started during adolescence. Objective: The aim of this study was to investigate GH treatment efficacy in short SGA children when treatment was star

  6. Does the time interval between antimüllerian hormone serum sampling and initiation of ovarian stimulation affect its predictive ability in in vitro fertilization-intracytoplasmic sperm injection cycles with a gonadotropin-releasing hormone antagonist?

    Polyzos, Nikolaos P; Nelson, Scott M; Stoop, Dominic


    To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response.......To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response....

  7. Glucagon-Like Peptide-1 Excites Firing and Increases GABAergic Miniature Postsynaptic Currents (mPSCs) in Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mice via Activation of Nitric Oxide (NO) and Suppression of Endocannabinoid Signaling Pathways

    Farkas, Imre; Vastagh, Csaba; Farkas, Erzsébet; Bálint, Flóra; Skrapits, Katalin; Hrabovszky, Erik; Fekete, Csaba; Liposits, Zsolt


    Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM–5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R. Whole-cell patch-clamp measurements demonstrated increased excitatory GABAergic miniature postsynaptic currents (mPSCs) frequency after Exendin-4 administration, which was eliminated by the GLP-1R antagonist Exendin-3(9–39) (1 μM). Intracellular application of the G-protein inhibitor GDP-β-S (2 mM) impeded action of Exendin-4 on mPSCs, suggesting direct excitatory action of GLP-1 on GnRH neurons. Blockade of nitric-oxide (NO) synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 100 μM) or N5-[Imino(propylamino)methyl]-L-ornithine hydrochloride (NPLA; 1 μM) or intracellular scavenging of NO by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO; 1 mM) partially attenuated the excitatory effect of Exendin-4. Similar partial inhibition was achieved by hindering endocannabinoid pathway using cannabinoid receptor type-1 (CB1) inverse-agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(1-piperidyl) pyrazole-3-carboxamide (AM251; 1 μM). Simultaneous blockade of NO and endocannabinoid signaling mechanisms eliminated action of Exendin-4 suggesting involvement of both retrograde machineries. Intracellular application of the transient receptor potential vanilloid 1 (TRPV1)-antagonist 2E-N-(2, 3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-(1, 1-dimethylethyl)phenyl]-2-Propenamide (AMG9810; 10 μM) or the fatty acid amide hydrolase (FAAH)-inhibitor PF3845 (5 μM) impeded the GLP-1-triggered endocannabinoid

  8. Ovarian, hormonal, and reproductive events associated with synchronization of ovulation and timed appointment breeding of Bos indicus-influenced cattle using intravaginal progesterone, gonadotropin-releasing hormone, and prostaglandin F2alpha.

    Saldarriaga, J P; Cooper, D A; Cartmill, J A; Zuluaga, J F; Stanko, R L; Williams, G L


    The objectives of this study were to 1) compare cumulative pregnancy rates in a traditional management (TM) scheme with those using a synchronization of ovulation protocol (CO-Synch + CIDR) for timed AI (TAI) in Bos indicus-influenced cattle; 2) evaluate ovarian and hormonal events associated with CO-Synch + CIDR and CO-Synch without CIDR; and 3) determine estrual and ovulatory distributions in cattle synchronized with Select-Synch + CIDR. The CO-Synch + CIDR regimen included insertion of a controlled internal drug-releasing device (CIDR) and an injection of GnRH (GnRH-1) on d 0, removal of the CIDR and injection of PGF2alpha (PGF) on d 7, and injection of GnRH (GnRH-2) and TAI 48 h later. For Exp. 1, predominantly Brahman x Hereford (F1) and Brangus females (n = 335) were stratified by BCS, parity, and day postpartum (parous females) before random assignment to CO-Synch + CIDR or TM. To maximize the number of observations related to TAI conception rate (n = 266), an additional 96 females in which TM controls were not available for comparison also received CO-Synch + CIDR. Conception rates to TAI averaged 39 +/- 3% and were not affected by location, year, parity, AI sire, or AI technician. Cumulative pregnancy rates were greater (P breeding season in CO-Synch + CIDR (74.1 and 95.9%) compared with TM (61.8 and 89.7%). In Exp. 2, postpartum Brahman x Hereford (F1) cows (n = 100) were stratified as in Exp. 1 and divided into 4 replicates of 25. Within each replicate, approximately one-half (12 to 13) received CO-Synch + CIDR, and the other half received CO-Synch only (no CIDR). No differences were observed between treatments, and the data were pooled. Percentages of cows ovulating to GnRH-1, developing a synchronized follicular wave, exhibiting luteal regression to PGF, and ovulating to GnRH-2 were 40 +/- 5, 60 +/- 5, 93 +/- 2, and 72 +/- 4%, respectively. In Exp. 3, primiparous Brahman x Hereford, (F1) heifers (n = 32) and pluriparous cows (n = 18) received the

  9. Correlation of the expression of gonadotropin releasing hormone and its receptor in human gastric adenocarcinoma cell proliferation and differentiation%GnRH及其受体的表达与胃腺癌细胞增殖和分化的相关性研究

    孙绪德; 柴伟; 高昌俊; 张贵和; 陈蕾; 黄威权


    AIM:To investigate the possible correlation of the expression of gonadotropin releasing hormone(GnRH) and its receptor with of proliferating cell nuclear antigen(PCNA) in human gastric adenocarcinoma cell proliferation and differentiation.METHODS:GnRH and its receptor and PCNA were detected in 30 gastric adenocarcinoma by immunohistochemical ABC technique. RESULTS:GnRH and its receptor had the same distribution pattern in gastric adenocarcinoma cells.The positive signal was found mainly in cytoplasm.The content of GnRH and its receptor immunoreative product in high differentiatied adenocarcinoma was significantly higher than those of the other two groups and the low differentiatied adenocarcinoma was the lowest(P< 0.05).PCNA positive signal which was found mainly in nucleus was gradually abated along with the raising of the extent of the differentiation.The differences were significant among the three groups(P< 0.05). In human gastric adenocarcinoma,the expression of GnRH and its receptor was negative correlation with the expression of PCNA(r=0.9).CONCLUSION:GnRH might be involved in the regulation of human gastric adenocarcinoma cell proliferation and differentiation.


    AbstractSeveral studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has inhibitory effects on ovulation. This action may be the result of either direct effect(s) of TCDD on ovarian function or via altered secretion of pituitary luteinizing hormon...

  11. Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women

    J. Aleknavičiūtė (Jūratė); J.H.M. Tulen (Joke); Timmermans, M. (Mirjam); Y.B. de Rijke (Yolanda); E.F.C. van Rossum (Liesbeth); F.H. de Jong (Frank); S.A. Kushner (Steven)


    textabstractSTUDY QUESTION Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? SUMMARY ANSWER Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. WHAT IS KNOWN ALREADY In

  12. 促性腺激素释放激素及多巴胺对斜带石斑鱼生长激素分泌及其mRNA表达的调控%Stimulatory effects of gonadotropin-releasing hormone and dopamine on growth hormone release and growth hormone mRNA expression in Epinephelus coioides

    冉雪琴; 李文笙; 林浩然


    研究斜带石斑鱼生长激素分泌及其mRNA表达的调控规律对于性别分化的控制、临床药物的选择,以及石斑鱼的增养殖等均具有重要的理论意义和实践意义.本文应用静态孵育系统,采用放射免疫测定法和化学发光液相杂交实验,研究GnRH和DA对斜带石斑鱼GH分泌、GH mRNA合成的调控作用.100 nmol/L sGnRH作用斜带石斑鱼脑垂体碎片1~24 h,明显促进GH的释放和GH mRNA的合成,并具有时间依存性;10 nmol/L~1μmol/L sGnRH作用1 h能明显促进斜带石斑鱼脑垂体释放GH,促进GH mRNA的合成,表现出明显的剂量效应.100 nmol/L、1μmol/L mGnRH作用1 h以一定的剂量依存方式促进GH的释放、促进GH mRNA的合成,但mGnRH的效应比相应剂量的sGnRH的作用弱.APO为DA受体的非选择性激动剂,不同剂量APO对斜带石斑鱼脑垂体碎片的作用结果显示,10 nmol/L~lμmol/L APO以剂量依存方式促进斜带石斑鱼脑垂体碎片释放GH、促进GH mRNA的合成;1μmol/L APO作用12 h以上明显促进GH的释放和GH mRNA的合成,并随时间的延长而增加.与sGnRH对斜带石斑鱼GH释放、GH mRNA合成的作用相比,APO的作用较弱.本文研究结果证实GnRH和DA能促进斜带石斑鱼脑垂体GH释放和GH mRNA合成.%Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth hormone (GH) release, but their effects on GH mRNA synthesis are controversial and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a hermaphroditic marine fish with sex reversal. Few data are available concerning the regulation of GH in grouper. In the present study, the effects of GnRH and DA on GH release and GH mRNA expression were determined using pituitary fragments of orange-spotted grouper under static culture conditions. After incubation from 1 h to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and increased the level of GH mRNA time-dependently. The minimum duration of s

  13. Comparative gene expression of gonadotropins (FSH and LH) and peptide levels of gonadotropin-releasing hormones (GnRHs) in the pituitary of wild and cultured Senegalese sole (Solea senegalensis) broodstocks.

    Guzmán, J M; Rubio, M; Ortiz-Delgado, J B; Klenke, U; Kight, K; Cross, I; Sánchez-Ramos, I; Riaza, A; Rebordinos, L; Sarasquete, C; Zohar, Y; Mañanós, E L


    The Senegalese sole (Solea senegalensis) is a valuable flatfish for aquaculture, but it presents important reproductive problems in captivity. Spawning is achieved by wild-caught breeders but cultured broodstocks fail to spawn spontaneously and, when they do, eggs are unfertilized. To gain knowledge on the physiological basis underlying this reproductive dysfunction, this study aimed at analyzing comparative hormone levels between wild and cultured broodstocks at the spawning season. The Senegalese sole gonadotropin (GTH) subunits, FSHbeta, LHbeta and GPalpha, were cloned and qualitative (in situ hybridization) and quantitative (real-time PCR) assays developed to analyze pituitary GTH gene expression. In females, FSHbeta and GPalpha mRNA levels were higher in wild than in cultured broodstocks, whereas in males all three subunits were highest in cultured. By ELISA, three GnRH forms were detected in the pituitary, displaying a relative abundance of GnRH2>GnRH1>GnRH3. All GnRHs were slightly more abundant in wild than cultured females, whereas no differences were observed in males. Plasma levels of vitellogenin and sex steroids were also analyzed. Results showed endocrine differences between wild and cultured broodstocks at the spawning period, which could be related to the endocrine failure of the reproductive axis in cultured breeders.

  14. Use of gonadotropin-releasing hormone agonist trigger during in vitro fertilization is associated with similar endocrine profiles and oocyte measures in women with and without polycystic ovary syndrome.

    O'Neill, Kathleen E; Senapati, Suneeta; Dokras, Anuja


    To compare endocrine profiles and IVF outcomes after using GnRH agonists (GnRHa) to trigger final oocyte maturation in women with polycystic ovary syndrome (PCOS) with other hyper-responders. Retrospective cohort study. Academic center. Forty women with PCOS and 74 hyper-responders without PCOS. GnRHa trigger. Number of oocytes. Serum E2, LH, and P levels on the day of GnRHa trigger and the day after trigger did not differ significantly between groups. There were no significant differences in total number of oocytes or percent mature oocytes obtained between groups after controlling for age, antral follicle count, and total days of stimulation. The overall rate of no retrieval of oocytes after trigger was low (2.6%). Fertilization, implantation, clinical pregnancy, and live-birth rates were similar in the two groups. No patients developed ovarian hyperstimulation syndrome (OHSS). The similar post-GnRHa trigger hormone profiles and mature oocyte yield support the routine use of GnRHa trigger to prevent OHSS in women with PCOS. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications.

    Seminara, Stephanie B; Dipietro, Meloni J; Ramaswamy, Suresh; Crowley, William F; Plant, Tony M


    The effect of continuous administration of the C-terminal fragment of metastin, the ligand for the G protein-coupled receptor, GPR54, on GnRH-induced LH secretion was examined in three agonadal, juvenile male monkeys whose responsiveness to GnRH was heightened by pretreatment with a chronic pulsatile iv infusion of synthetic GnRH. After bolus injection of 10 microg human (hu) metastin 45-54 (equivalent to kisspeptin 112-121), the GPR54 agonist was infused continuously at a dose of 100 microg/h and elicited a brisk LH response for approximately 3 h. This rise was then followed by a precipitous drop in LH despite continuous exposure of GPR54 to metastin 45-54. On d 4, during the final 3 h of the infusion, single boluses of hu metastin 45-54 (10 microg), N-methyl-DL-aspartic acid (NMDA) (10 mg/kg) and GnRH (0.3 microg) were administered to interrogate each element of the metastin-GPR54-GnRH-GnRH receptor cascade. Although the NMDA and GnRH boluses were able to elicit LH pulses, that of hu metastin 45-54 was not, demonstrating functional integrity of GnRH neurons (NMDA) and GnRH receptors (NMDA and GnRH) but desensitization of GPR54. The desensitization of GPR54 by continuous hu metastin 45-54 administration has therapeutic implications for a variety of conditions currently being treated by GnRH and its analogs, including restoration of fertility in patients with abnormal GnRH secretion (i.e. idiopathic hypogonadotropic hypogonadism and hypothalamic amenorrhea) and selective, reversible suppression of the pituitary-gonadal axis to achieve suppression of gonadal steroids (i.e. precocious puberty, endometriosis, uterine fibroids, and prostate cancer).

  16. Variation in kisspeptin and RFamide-related peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: a novel medium for seasonal breeding in the sheep.

    Smith, Jeremy T; Coolen, Lique M; Kriegsfeld, Lance J; Sari, Ika P; Jaafarzadehshirazi, Mohammad R; Maltby, Matthew; Bateman, Katherine; Goodman, Robert L; Tilbrook, Alan J; Ubuka, Takayoshi; Bentley, George E; Clarke, Iain J; Lehman, Michael N


    Reproductive activity in sheep is seasonal, being activated by short-day photoperiods and inhibited by long days. During the nonbreeding season, GnRH secretion is reduced by both steroid-independent and steroid-dependent (increased response to estradiol negative feedback) effects of photoperiod. Kisspeptin (also known as metastin) and gonadotropin-inhibitory hormone (GnIH, or RFRP) are two RFamide neuropeptides that appear critical in the regulation of the reproductive neuroendocrine axis. We hypothesized that expression of kisspeptin and/or RFRP underlies the seasonal change in GnRH secretion. We examined kisspeptin and RFRP (protein and mRNA) expression in the brains of ovariectomized (OVX) ewes treated with estradiol (OVX+E) during the nonbreeding and breeding seasons. In OVX+E ewes, greater expression of kisspeptin and Kiss1 mRNA in the arcuate nucleus and lesser expression of RFRP (protein) in the dorsomedial nucleus of the hypothalamus were concurrent with the breeding season. There was also a greater number of kisspeptin terminal contacts onto GnRH neurons and less RFRP-GnRH contacts during the breeding season (compared with the nonbreeding season) in OVX+E ewes. Comparison of OVX and OVX+E ewes in the breeding and nonbreeding season revealed a greater effect of steroid replacement on inhibition of kisspeptin protein and Kiss1 mRNA expression during the nonbreeding season. Overall, we propose that the two RFamide peptides, kisspeptin and RFRP, act in concert, with opposing effects, to regulate the activity of GnRH neurons across the seasons, leading to the annual change in fertility and the cyclical seasonal transition from nonbreeding to breeding season.

  17. Central precocious puberty and gonadotropin releasing hormone agonist treatment

    W. Oostdijk (Wilma)


    textabstractIn order to understand the processes occurring during precocious puberty, one needs to specify what is currently known about normal pubertal development. Puberty can be defined as a maturational process of the hypothalamic-pituitarygonadal axis, which results in the development of the go

  18. IVF-ET中促性腺激素释放激素激动剂的超促排卵应用与剂量研究%Gonadotropin-releasing Hormone Agonist for Controlled Ovarian Hyperstimulation and Dose-finding Study in In Vitro Fertilization-Embryo Transfer

    郜虹媛; 匡延平


    Gonadotropin-releasing hormone agonist(GnRH-a) is one of the most effective drugs used for controlled ovarian hyperstimulation (COH) in in vitro fertilization-embryo transfer (IVF-ET). The early "flare up" of GnRH-a can stimulate the sharp release of endogenous gonadotropins. Continuous administration of GnRH-a caused reversibly block of pituitary function and low level of endogenous gonadotropin, which is the so-called down-regulation. Therefore, GnRH agonist protocol with exogenous gonadotropins can prevent a luteinizing nor-mone surge, premature oocyte maturation and luteinization. In addition, GnRH-a triggering which can take the place of hCG triggering leads to a significant reduction of OHSS rate. To explore the effective low dose of GnRH-a which can prevent a LH surge without excessive pituitary desensitization has a critical role for COH.%促性腺激素释放激素激动剂(GnRH-a)是体外受精-胚胎移植(IVF-ET)技术中重要用药.GnRH-a与GnRH受体结合后,早期"突发"作用可刺激垂体促性腺激素急剧释放,持续应用后使垂体受抑制,内源性促性腺激素(Gn)水平下降,即所谓的降调节作用.利用这种生物学特性,GnRH-a联合Gn超促排卵可预防早发黄体生成素(LH)峰,避免卵泡过早黄素化.另外,GnRH-a代替人绒毛膜促性腺激素诱发排卵可降低卵巢过度刺激综合征(OHSS)发生率.探索既能有效抑制LH峰,又不使垂体过度抑制的GnRH-a有效低剂量对于超促排卵有重要意义.

  19. 促性腺激素释放激素基因(GnRH)和生长激素基因(GH)对番鸭产蛋性能的遗传效应分析%Genetic Effects of Gonadotropin-releasing Hormone (GnRH) and Growth Hormone (GH) Genes on the Egg Performance in Muscovy Duck(Cairina moschata)

    吴旭; 严美姣; 刘丽平; 连森阳; 傅星源; 王光瑛; 李昂


    Gonadotropin-releasing hormone (GnRH) and growth hormone (GH), which control the reproductive performance of animal, are secreted by hypothalamus pituitary gonadal axis and GH/IGF axis. The single nucleotide polymorphism of GnRH and GH genes was detected for the association with egg performance in white muscovy duck (Cairina moschata) RF line which came from Putian Guangdong Wenshi Poultry Co., Ltd.. PCR-SSCP method was used for identification of genotypes. The results showed that three genotypes AA, AB and BB were found in GnRH gene and a mutation G→A was found by DNA sequencing. Three genotypes CC, CD and DD were found in GH gene and a mutation A→G was found by DNA sequencing. Chi-square test indicated that the two polymorphism sites fitted Hardy-Weinberg equilibrium (P>0.05).The frequency of A/B alleles in thepopulation was for GnRH 0.675 and 0.325, and for GH 0.667 and 0.333. GnRH genotype had been showed a significant difference in the egg number of 300 d (P0.05). The general linear model (GLM) analysis results showed that both of GnRH and GH genes showed mainly in the pattern of additive effect and all the dominant effects were not significant. The additive effect of GnRH gene in the egg number of 300 d and the highest clutch days were -3.53 and -3.33, respectively. The additive effect of GH gene in the highest clutch days was -2.44. It implies that the GnRH and GH genes can be candidate genes locus or linked mark to the major gene, which affect the laying traits significantly in Muscovy duck.%促性腺激素释放激素(GnRH)和生长激素(GH)分别是下丘脑-垂体-性腺轴(HPG)与GH/IGF轴分泌的激素,共同参与调控动物的繁殖性能.本研究以白羽番鸭(Cairina moschata)RF系为实验材料,采用PCR-SSCP技术进行基因分型,同时建立适合的线性统计模型,分析基因型与产蛋性能的关联性.结果表明,GnRH基因5’调控区检测到3种基因型AA/AB/BB,经测序比对AA型与BB型相比发

  20. Effect of Modified Prolonged Gonadotropin - releasing Hormone Agonist Therapy on the Outcome of the in vitro Fertilization - embryo Transfer in Patients with Endometriosis%不同剂量GnRH-a超长降调节在EMs患者中的应用研究



    目的 探讨不同剂量促性腺激素释放激素激动剂(gonadotropin - releasing hormone agonist,GnRH -a)超长降调节对改善子宫内膜异位症( endometriosis,EMs)患者体外受精/胚胎移植(IVF - ET)结局的作用.方法 将50例子宫内膜异位症患者(腹腔镜术后)随机分为两组接受改良超长方案治疗,A组(末次半量组):30例患者GnRH -a治疗3~6个月,每次1.88mg(1/2支)达菲林肌内注射,间隔28天,第2次注射达菲林后2周开始检测血清CA125,CA125降至18U/L以下后注射末次达菲林1/2支;B组(末次0.375mg组):20例患者末次治疗剂量改为0.375mg( 1/10支)达菲林肌内注射.两组均于末次达菲林注射后2~6周开始尿促性腺激素(human menopausal gonadotropin,HMG)225~ 300U(3~4支)肌内注射促进卵泡发育,于最大卵泡直径≥16mm时注射绒毛膜促性腺激素(human chronic gonadotropin,HCG) 5000 ~ 10000U,32 ~ 36h后取卵,取卵后48 ~72h胚胎移植.结果 启动日黄体生成素( luteinizing hormone,LH)水平A组低于B组,差异有统计学意义(P=0.04).A组HCG日孕酮(progesterone,P)水平低于B组,差异有统计学意义(P=0.05),B组有2例HCG日P升高至3.0ng/ml以上.A组受精率0.77±0.03,高于B组,差异有统计学意义(P=0.02).平均用药天数,总剂量,两组比较差异无统计学意义(P>0.05).平均获卵数,优质胚胎率,种植率,妊娠率,两组比较差异无统计学意义(P>0.05).A组妊娠率69%,B组妊娠率50%,均高于本中心同期子宫内膜异位症患者行超长后短方案组妊娠率(40.05%).结论 两种剂量GnRH -a超长降调节治疗在子宫内膜异位症患者中应用均改善了其IVF结局,0.375mg GnRH -a可能不能全程抑制自发LH峰,可能仍需联合短方案才能达到预期目的,但由于抑制程度轻,对卵巢功能低下的妇女可能获得较好的结局.%Objective To investigate the outcome of in vitro fertilization and embryo transfer (IVF - ET) in patients with

  1. 光照应激对SD大鼠睾丸促性腺激素释放激素受体表达的影响%Light stress and the expression of gonadotropin-releasing hormone receptor in the testis of SD rats

    时姗姗; 马恒辉; 章如松; 周航波; 陶晓倩; 柳海燕; 林杈英; 姚兵


    Objective Many kinds of stress can suppress reproduction, but systematic researches are yet absent on its regulatory mechanism. The aim of this study was to observe the changes in the expression of the ( gonadotropin-releasing hormone) GnRH receptor in the testis of SD rats under constant light stress. Methods We established short-term (2, 3, 4, and 7 days) and long-term ( 14 , 21 and 28 days) light-stress models in 70 SD rats , and exposed them to round-the-clock light ( the experimental group) and normal daylight ( the control group) . Then we collected the testis tissues of the rats for the analysis of the changes in the GnRHR expression by Westem blot and RT-PCR and determination of the testosterone level in the serum using a chemoluminescent technique. Results Compared with the control group, the GnRHR expression showed no significant changes in the experimental group at 2, 3 , 4 and 7 days , but was increased (27.8 ± 11.2) % (P<0.05), (40.6 ± 24. 8) % (P<0.05) and (26. 1 ± 33.6) % (P>0.05) at 14, 21 and 28 days, respectively. The mRNA expression of GnRHR exhibited a similar increase to its protein expression, but with no statistically significant difference. The level of testosterone was significantly elevated with the increased time of light stress in the experimental group as compared with the controls (P <0. 05). Conclusion The expression of the GnRH receptor changed with the increased time of light stress, which suggests that GnRHR could regulate reproductive function under light stress.%目的 多种应激方式均能抑制生殖功能,但其对调控机制仍缺少系统的研究.通过观察光照应激状态下 SD大鼠睾丸内促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)受体蛋白和mRNA表达变化,为寻找应激状态下生殖系统调节机制提供依据.方法 建立 SD大鼠光照应激模型,将70只大鼠随机分为14组,其中7组(实验组)24h持续光照,包括短期光照应激(2、3、4和7d

  2. Spontaneous ovulation in in vitro fertilization-embryo transfer cycles using gonadotropin-releasing hormone antagonist:a large-sample retrospective study%GnRH拮抗剂方案在体外受精-胚胎移植周期中自发排卵风险的大样本量回顾性研究

    罗璐; 陈明晖; 贾梦希; 王琼; 周灿权


    Objective To investigate the premature spontaneous ovulation rates in in vitro fertilization-embryo transfer (IVF-ET) cycles using gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a), as well as the risk factors for premature spontaneous ovulation. Methods The rates of premature spontaneous ovulation in a total of 10 612 cycles using GnRH-ant or GnRH-a were compared. Matched case-controlled study and binary logistic regression model were conducted to analyze the risk factors for premature spontaneous ovulation. Results The spontaneous ovulation rate in the whole for GnRH-a cycles was 0.15%(13/8 514), compared with a 1.62%(34/2 098) in GnRH-ant cycles (P<0.01). Further matched controlled study and regression analyze found out that higher basal FSH level was a predominant risk and prediction factor for spontaneous ovulation (OR=1.20, P=0.009). Conclusions In GnRH-ant cycles, spontaneous ovulation rate is about 10 times than which in GnRH-a cycles. Diminished ovarian function is a predominate risk factor for premature spontaneous ovulation.%目的:探讨在体外受精-胚胎移植(IVF-ET)周期中促性腺激素释放激素拮抗剂(GnRH-ant)方案的自发排卵率,并分析自发排卵的高危因素。方法回顾性分析2012年1月至2015年12月中山大学附属第一医院在LVF-ET中使用GnRH-ant方案和促性腺激素释放激素激动剂(GnRH-a)长方案共10612个周期,计算GnRH-ant方案(2098个周期)的自发排卵总体情况,并与GnRH-a长方案(8514个周期)比较;进一步将GnRH-ant方案中发生自发排卵(自发排卵组)的周期(34个)与未发生自发排卵(未自发排卵组)的周期(136个)进行1∶4匹配的对照研究及二元logistic多因素回归分析,分析在GnRH-ant方案中发生自发排卵的高危因素。结果在总体人群中,GnRH-ant方案的自发排卵率为1.62%(34/2098),高于GnRH-a长方案的0.15%

  3. The effect of serum LH level on the day of superovulation start on the prolonged gonadotropin-releasing hormone agonist therapy on the outcomes of IVF-ET in patients with ovarian endometriosis cysts%超长降调节方案超排启动日血清LH水平对卵巢膜异位囊肿患者IVF-ET结局的影响

    杨海燕; 林文琴; 林金菊; 孟绿荷; 费前进


    Objective To evaluate the effect of serum LH level on the day of superovulation start on the prolonged gonadotropin-releasing hormone ngonist therapy on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in patents with ovarian endometriomas. Methods 75 patients with ovarian en-dometriomas were treated by laparoscopic cystectomy or laparotomy cystectomy or ultrasound-mediated cysts puncture, and gonadotropin-releasing hormone agonist (GnRH-α) was given for 3 to 4 times every 28 days after the operation. Superovulation started after 14 ~ 84 days of the last injection. All the patients were di-vided into two groups according to the level of serum LH. Group A included 30 patients whose level of LH was less than 0. 5IU/L, and group B included 45 patients whose level of LH was over 0.5IU/L and less than 1.5IU/L. The outcomes of IVF-ET were evaluated. Results The total ampoules of Gn administration and the ampoules of hMG needed in group A[(32.28±7.7) ampoules, ( 12.0±8. 9) ampoules,]were sig-nificantly more than that in group B[( 25.84±7. 1 ) ampoules, ( 6. 19±7.4) ampoules, P < 0.05] . The successful embryo implantation rate in group A( 18. 1% ) was lower than group B(26. 7% ), and the differ-ence has statistical significance ( P <0. 05). Conclusion The low level of serum LH on the superovula-lion day on the prolonged gonadotropin-releasing hormone agonist protocol will increase the ampoules of Gn administration and decrease the successful embryo implantation rate of IVF-ET, thus LH should be a more important reference parameter of superovulation start.%目的 探讨超长降调节方案超排启动日血清LH水平对卵巢内膜异位囊肿患者体外受精-胚胎移植(IVF-ET)结局的影响.方法 75例卵巢内膜异位囊肿患者在腹腔镜或开腹下行囊肿剥出术或经阴道B超引导下囊肿穿刺术后每28 d注射促性腺激素释放激素激动剂(GnRH-α)共3~4次,末次注射后14~84 d予促性腺激素(Gn)超排卵

  4. Gonadotrofina coriônica humana e hormônio liberador de gonadotrofina como indutores da reprodução do jundiá = Human chorionic gonadotropin and gonadotropin-releasing hormone as breeding inducers of jundiá

    Paulo César Falanghe Carneiro


    Full Text Available Este trabalho foi realizado com o objetivo de avaliar parâmetros reprodutivos de machos e fêmeas de jundiá adultos após a aplicação do HCG (gonadotrofina coriônica humana e do GnRHa (hormônio liberador do hormônio gonadotrópico e compará-los àqueles obtidos quando usado o extrato hipofisário da carpa comum. Etapa 1 (Machos - quatro grupos, com oito machos cada, receberam os seguintes tratamentos: M1: sem hormônio; M2: extrato hipofisário 0,5 mg kg-1; M3: HCG 200 UI kg-1; M4: GnRHa+inibidor dopaminergético 0,1 glóbulo(Ovopel® kg-1. Etapa 2 (fêmeas – 36 fêmeas foram divididas em cinco grupos: F1: extrato hipofisário em duas aplicações, 0,5 e 5,0 mg kg-1; F2: HCG em duas aplicações, 200 e 400 UI kg-1; F3: HCG 400 UI kg-1 em doseúnica; F4: HCG 1000 UI kg-1 em dose única; F5: GnRHa+inibidor dopaminergético 1 glóbulo(Ovopel® kg-1. O uso do extrato hipofisário da carpa comum aumentou significativamente o volume de sêmen liberado e estimulou maior quantidade de fêmeas à liberar óvulos. O HCG e o GnRHa não apresentaram resultados positivos no tocante à reprodução induzida do jundiá, nas doses utilizadas neste estudo.In this study we analyzed reproductive parameters of males and females of jundiá induced by HCG (human chorionic gonadotropin and GnRHa (gonadotropin-releasing hormone, and compared the results tothose using carp pituitary extract. Stage 1 (Males - four groups with eight males each received one of the following treatments: M1: without hormone; M2: pituitary extract 0.5 mg kg-1; M3: HCG 200 UI kg-1; M4: GnRHa+dopamine receptor antagonist 0.1 pellet (Ovopel® kg-1. Stage 2 (Females – thirty-six females were separated in 5 groups: F1: pituitary extract in two applications, 0.5 and 5.0 mg kg-1; F2: HCG in two applications, 200 and 400 UI kg-1; F3: HCG 400 UI kg-1 in a single dose; F4: HCG 1000 UI kg-1 in a singledose; F5: GnRHa+dopamine receptor antagonist 1 pellet (Ovopel® kg-1. The pituitary extract

  5. Clinical outcomes of prolonged gonadotropin-releasing hormone agonist(GnRH-a) therapy used in patients with good ovarian reserves and previous in vitro fertilization or intracytoplasmic sperm injection embryo transfer(IVF/ICSI-ET) failure cycle%超长方案在卵巢储备良好前次IVF/ICSI-ET失败患者中的应用分析

    聂玲; 伍琼芳; 张寅; 陈晶晶


    Objective : To evaluate the clinical outcomes of prolonged gonadotropm-releasing hormone agonist therapy( GnRH-a) used in patients with good ovanan reserves and previous in vitro fertilization or intracytoplasmic sperm injection embryo transfer( IVF/ICSI-ET) failure cycle. Methods : Retrospective analyze a total of 246 patients with previous IVF-ET failure cycle and good ovarian reserve who underwent the secondary IVF-ET cycles. Patients were divided into two groups : the study group included 52 patients applied with prolonged protocol;the control group included 194 patients applied with long protocol. Results : The numher of oocytes retrieved and the duration of gonadotropin ( Gn) were significantly higher in the study group(P<0. 01). But there were no significant differences in the dose of Gn,total numher of good quality embryos, mean endometrium thickness on transfer day ,mean serum P level on human chorionic gonadotrophin ( HCG) day and severe ovarian hyperstimulation syndrome ( OHSS) rate between the two groups (P> 0. 05). The positive HCG rate and clinical pregnancy rate( CPR) increased obviously in the study group, respectively ( 79. l% vs 61. 1% , P =0. 03 ;69. 8% vs 54. 9% , P=O. 048 ) . And there was an mcreasing tendency in implantation rate ( 39. 5% vs 31. 5% , P = 0. 18 ) . Conclusion : Using prolonged gonadotropin-releasing hormone agonist therapy in patients with good ovarian reserves and previous IVF-ET failure cycle may make the endometrium receptivity better than using the long protocol, and improve obviously the clinical pregnancy outcomes. So the prolonged protocol is recommendable.%目的:评估超长降调节方案在卵巢储备良好前次IVF/ICSI-ET失败患者中的应用效果.方法:回顾分析246例卵巢储备功能良好前次IVF/ICSI-ET常规长方案失败再次行助孕治疗的患者,其中超长方案治疗52例为研究组,常规长方案治疗194例为对照组.结果:研究组Gn时间及

  6. The effect of gonadotropin-releasing hormone agonist-induced down-regulation on pituitary and ovarian function%促性腺激素释放激素激动剂降调对垂体内外的影响

    朱桂金; 徐蓓; 聂睿


    catalytic subunit.40%-60% of follicle-stimulating hormone (FSH) secretion is repressed by the immediate action of downregulation,while 90% luteinizing hormone (LH) could be repressed, so downregulation is used to prevent the premature LH surges. Regulation of paracrine secretion by downregulation requires the involvement of FSH and LH and regulatory factors of paracrine secretion have no effect on the promotion of follicular development. The negative feedback of steroid hormone is through the level of hypothalamus and pituitary, while downregulation functions at the level of the gonadotropin-releasing hormone (GnRH) receptors, so the normal positive and negative feedbacks are cancelled by downregulation.There exist GnRH receptors in granulosa cells, theca cells and luteal cells, so it could be presumed theoretically that GnRH may have direct effects on ovary. Both animal experiments and in vitro studiessuggest that GnRH may have a direct action on ovarian granulosa cells through interfering steroid synthesis and follicular development. So except for preventing the premature LH surges and decreasing the detrimental effect of high LH, the effect of GnRH agonist-induced down-regulation increasing pregnancy rate may be also through the immediate action on follicular development, oocyte maturation and endometrial receptivity, but no confirmation has been made by the existing evidence.

  7. Effects of Gonadotropin-releasing Hormone (GnRH) and Dopamine on Gonadotropin(GTH) Secretion from in vitro Pituitary Cells of Rainbow Trout%促性腺激素释放激素和多巴胺对虹鳟( Oncorhynchus mykiss )离体脑垂体细胞分泌促性腺激素的影响



    本文研究了不同性腺发育时期淡水饲养的雌雄虹鳟(Oncorhynchus mykiss)血浆促性腺激素(GTH)浓度的变化规律;以及在离体条件下,探讨了促性腺激素释放激素(GnRH)、GnRH拮抗物和多巴胺对虹鳟脑垂体细胞分泌促性腺激素(GTH-Ⅱ)的影响。结果表明:(1)在雄性,血浆中GTH-Ⅱ的水平随性腺发育而逐渐增高;在雌性,仅排卵期血浆中GTH-Ⅱ的水平明显增高。(2)未成熟期和成熟期的雌性虹鳟脑垂体细胞对sGnRH和cGnRH刺激的敏感性表现不尽相同。成熟期和排卵后的脑垂体细胞对GnRH的刺激较为敏感,GTH-Ⅱ的分泌量较多。(3)在没有sGnRH的存在下,GnRH拮抗物对GTH-Ⅱ的分泌不发生作用,而在sGnRH的存在下,GnRH拮抗物对GTH-Ⅱ的分泌表现出浓度依赖的抑制作用。(4)在没有sGnRH的存在下,多巴胺对GTH-Ⅱ的分泌不发生作用,而当多巴胺的浓度一定时,随着sGnRH浓度的增加,GTH-Ⅱ分泌的量增大。另外,不论sGnRH还是cGnRH都不影响不同时期的脑垂体细胞GTH-I的分泌这些结果可为虹鳟的人工催产提供一些理论依据。%Plasma gonadotropin (GTH) levels during immature, mature and ovulated periods and effects of gonadotropin-releasing hormone (GnRH) and dopamine on GTH secretion of in vitro pituitary cells of rainbow trout were investigated. Plasma GTH levels increased with gonadal development. The different effects of sGnRH and cGnRH on GTH- Ⅱ secretions of pituitary cells in vitro from immature, mature and ovulated periods of rainbow trout were observed. GnRH antagonist did not change GTH - Ⅱ contents under the absence of sGnRH while GnRH antagonist suppressed dose-dependently GTH- Ⅱ secretions of pituitary cells in combination with sGnRH.Dopamine also did not affect GTH- Ⅱ levels under the absence of sGnRH, while GTH- Ⅱ secretions of pituitary cells were enhanced when the dosage of sGnRH was increased with the presence of

  8. 使用促性腺激素释放激素激动剂中妊娠37例分析%Analysis of 37 pregnancies unexpectedly exposured to gonadotropin-releasing hormone agonist during in vitro fertilization and embryo transfer

    陈霞; 赵军招; 周玮; 叶碧绿


    目的 探讨在体外受精-胚胎移植(IVF-ET)的过程中使用促性腺激素释放激素激动剂(GnRH-a)后意外妊娠的原因及结局.方法 回顾性分析2005年1月至2010年12月行IVF-ET超排卵周期使用GnRH-a过程中发生妊娠的临床资料.结果 在7,086个IVF-ET超排卵周期使用GnRH-a过程中发现妊娠37例,发生率为0.52%.37例妊娠中宫内妊娠24例,其中17例已经分娩健康新生儿,6例继续妊娠中,胎儿宫内发育良好,1例孕8个月早产;1例B超检查提示宫内胚胎停育行清宫术,2例自然流产,流产发生率为8.1%(3/37);异位妊娠6例,发生率为16.2%(6/37);生化妊娠2例;失访2例.结论 在IVF长方案中,使用GnRH-a可导致意外妊娠,且有良好的妊娠结局.%Objective: To summarize the causation and outcome of unexpected pregnancy exposed to gonadotropin-releasing hormone agonist (GnRH-a) during in vitro fertilization and embryo transfer (IVFET).Methods: From Jan 2005 to Dec 2010, a total of 37 cases.with unexpected pregnancy exposed to GnRH-a during their controlled ovarian hyperstimulations were retrospectively analyzed in this study.Results: Thirty seven women exposed to GnRH-a during their controlled ovarian hyperstimulations became pregnant in 7,086 IVF-ET cycles.The unexpected pregnancy rate was 0.52% (37/7,086).Among 37 unexpected pregnancies, seventeen babies were born alive and one was preterm birth in month 8 of pregnancy.Six pregnancies are ongoing.The abortion rate was 8.1% (3/37).The ectopic pregnancy rate was 16.2% (6/37).Two women were with biochemical pregnancy.Two women were lost to follow up.Conclusions: Our findings suggested that the using GnRH-a for controlled ovarian hyperstimulation could lead to unexpected pregnancy and have good pregnancy outcome.

  9. Effect of combined treatment of minidose estrogen and gonadotropin releasing hormone analogues for children with idiopathic central precocious puberty%小剂量雌激素联合促性腺激素释放素类似物治疗儿童特发性中枢性性早熟

    赵岫; 张琴; 高晓杰


    目的 观察小剂量雌激素联合促性腺激素释放素类似物(GnRHa)治疗特发性中枢性性早熟(ICPP)的效果.方法 45例ICPP伴生长减速患儿分为3组:雌激素联合GnRHa治疗组、重组人生长激素(rhGH)联合GnRHa治疗组、单纯GnRHa治疗组,每组15例.分别于治疗前和治疗6个月后观察3组患儿骨龄(BA)、年生长速率(GV)、体质量、身高(Ht)、骨龄身高(Htba)、成年预测身高(PAH)、血脂、血糖、胰岛素、甲状腺功能、雌二醇(E2)、睾酮(T)、泌乳素(PRL)、血胰岛素样生长因子1(IGF-1)、乳房及子宫卵巢B超等的变化;另行GnRH激发试验监测促黄体生成素(LH)和促卵泡雌激素(FSH)水平.结果 3组患儿治疗前Ht、Htba、骨龄/年龄(BA/CA)、PAH、GV、体质量、IGF-1比较差别均无统计学意义(P>0.05).治疗6个月后,雌激素联合GnRHa治疗组患儿GV、Ht、PAH明显高于治疗前(P<0.05),rhGH联合GnRHa治疗组患儿GV.、Ht、PAH、IGF-1明显高于治疗前(P<0.05);且雌激素联合GnRHa治疗组和rhGH联合GnRHa治疗组患儿GV、Ht、PAH明显高于单纯GnRHa治疗组(P<0.05);rhGH联合GnRHa治疗组患儿IGF-1明显高于雌激素联合GnRHa治疗组和单纯GnRHa治疗组(P<0.05).3组治疗前后E2、T、PRL、乳房及子宫和卵巢B超结果均无明显变化,GnRH激发试验LH、FSH和LH/FSH亦无明显变化(P>0.05).结论 小剂量雌激素联合GnRHa治疗ICPP,能在不加速BA的情况下有效地提高生长速率,且雌激素价格便宜,患者依从性好.%Objective To assess the effect of combined treatment of minidose estrogen and gonadotropin releasing hormone analogues (CnRHa) for children with idiopathic central precocious puberty (ICPP). Methods Forty-five female patients with ICPP and growth deceleration were divided into three groups:estrogen plus GnRHa group,recombinant human growth hormone (rhGH) plus GnRHa group and GnRHa group, fifteen patients in each group. The bone age (BA ) , growth

  10. Effects of “two fairy decoction”(二仙汤) and its decomposed recipe on gonadotropin-releasing hormone secreted by GT1-7 cell line%二仙汤及其拆方对GT1-7细胞株GnRH分泌的影响

    杨颖; 陈名道; 李凤英; 唐金凤; 高国锋; 陈家伦


    目的:GT1-7细胞株是转入了猴病毒-40的T抗原(SV40T)癌基因的促性腺激素释放激素(GnRH)神经内分泌细胞株。本实验观察补肾方二仙汤及其“温肾”、“滋阴”两个拆方对GT1-7细胞株释放GnRH的影响。方法:(1)3个月龄的SD雄性大鼠予成人每公斤体重的10倍剂量灌服中药4日,于末次给药后1或2小时腹主动脉取血,制备成药物血清。(2)氯胺T法标记GnRH,建立稳定可靠的放免标准曲线。(3)GT1-7细胞用含10%、30%或50%药物血清的培养液孵育24或48小时,收集上清液做放射免疫测定。结果:(1)末次给药后1、2小时取血的二仙汤药物血清均能刺激GnRH释放,以1小时给药血清效果最好。(2)10%浓度的药物血清为最有效剂量。(3)二仙汤全方及其两个拆方均能促进GnRH释放,以全方效果最显著。结论:中医“肾主生殖”的功能似涉及下丘脑GnRH神经元及其调控性腺轴的功能,二仙汤及其全方能够直接调节GnRH的分泌。%To investigate the effects of kidney tonifying formula “two fairy decoction”(TFD,二仙汤) and its two decomposed recipes “kidney warming”(温肾) and “yin nourishing”(滋阴) of ingredients on GT1-7 cell line which was developed by targeting the SV40T antigen to gonadotropin-releasing hormone(GnRH) neuron in transgenic mouse.Methods:(1)Three months-aged male rats were orally administered herbal extract for four days,sera were obtained from rats one or two hours after the last administration.(2)GnRH was measured by radioimmunoassay(RIA) with chloramine T iodination,and the detectable limit was 0.25 pg.(3)Cells were maintained for 24 or 48 hours with DMEM which contained 10%,30% and 50% rat serum,and samples were collected for RIA measurements.Results:(1)Both sera obtained from one and two hours after the last oral herb administration of TFD stimulated GnRH secretion,the former seemed more potent.(2

  11. GnRHa联合反向添加疗法治疗子宫内膜异位症对腰椎骨量的影响%Effect of gonadotropin releasing hormone agonist combined with add - back therapy on bone mineral density of lumbar vertebrae in treatment of endometriosis

    陈珣; 张绍芬


    Objective; To research and compare the effects of gonadotropin releasing hormone agonist (GnRHa) combined with percutaneous injection of estrogen and add - back therapy with oral administration of medroxyprogesterone acetate and GnRHa alone on bone mineral density of lumbar vertebrae in treatment of endometriosis. Methods; Twenty - eight patients with endometriosis were selected, all of them were diagnosed definitely by laparoscopy within two months, then they were randomly divided into CnRHa alone group (group A) and GnRHa plus add -back therapy group (group B) . The patients in group A were treated with percutaneous injection of Zoladex on the second day during menstrual cycle or at 3 - 5 days after operation; percutaneous injection was conducted every 28 days for three times; while the patients in group B were treated with percutaneous injection of Zoladex on the second day during menstrual cycle or at 3 - 5 days after operation, percutaneous injection was conducted every 28 days for three times, at the same time, half of patch was pasted on the abdominal skin every week from percutaneous injection for the first time, and they were treated with oral administration of medroxyprogesterone acetate (6 mg) every night until the end of treatment Bone mineral density of lumbar vertebrae was measured before treatment, at the same time, peripheral venous blood samples were obtained to detect the levels of estradiol and serum BGP; the above - mentioned indexes were reexam-ined at three months after treatment Results-. In group A, the bone mineral densities of LI - L4 at three months after treatment were significantly lower than those before treatment (P < 0. 01); while in group B, compared with before treatment, the bone mineral densities of LI -L4 at three months after treatment showed decreasing trends, but there was no significant difference (P =0. 201) . In group A, the serum level of BGP after treatment was significantly higher than that before treatment ( P < 0. 01

  12. 促性腺激素释放激素激动剂用于辅助生殖技术黄体支持的荟萃分析%Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles:a systematic review and Meta-analysis

    余璐萍; 刘宁; 刘英


    目的系统评价促性腺激素释放激素激动剂(GnRH-a)用于辅助生殖技术(ART)黄体支持后,对妊娠结局产生的影响。方法计算机检索PubMed数据库、EMBASE数据库、Cochrane图书馆、随机对照试验(RCT)注册中心[WHO国际临床试验注册平台(ICTRP)和]、中国生物医学文献数据库(CBM)、中国知网(CNKI)数据库及万方医学数据库中发表于2015年11月之前的原创性研究论文;收集在体外受精(IVF)或卵母细胞胞质内单精子注射(ICSI)中,GnRH-a应用于黄体支持的RCT文献。根据Cochrane系统评价方法,由2位评价员根据纳入及排除标准独立进行文献筛选、资料提取和质量评价后,采用Stata 13.0软件对符合质量标准的RCT文献进行荟萃分析,分析GnRH-a用于ART黄体支持后对妊娠结局产生的影响。结果共纳入11项研究,3406例患者,3280个周期。以采用标准黄体支持方案的研究人群为对照组,在标准黄体支持方案基础上加入GnRH-a的研究人群为试验组。试验组与对照组比较,出生率或继续妊娠率(RR=1.29,95%CI为1.11~1.51)、临床妊娠率(RR=1.24,95%CI为1.08~1.43)、多胎率(RR=1.95,95%CI为1.21~3.14)均明显增加。结论目前的证据表明,无论采用激动剂方案或拮抗剂方案降调,在黄体支持中加入GnRH-a均可增加出生率或继续妊娠率、临床妊娠率、多胎率,可为ART过程中的黄体支持提供新的治疗方案。%Objective To evaluate the potential efficacy and safety of gonadotropin-releasing hormone agonist(GnRH-a) administration in the luteal-phase on in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles in assisted reproductive technology (ART). Methods The relevant papers published before November 2015 were electronically searched in PubMed, EMBASE, Cochrane Library, WHO ICTRP,, CNKI, CBM and Wan

  13. Safety of gonadotropin releasing hormone analogue combined with Cy-clophosphamide in the treatment of patients with systemic lupus erythe-matosus%促性腺释放激素类似物联合环磷酰胺治疗系统性红斑狼疮的安全性

    林琦; 王庆文; 黄倩羽; 蔡月明; 黄星涛; 魏蔚霞


    目的:探讨促性腺释放激素类似物(GnRHa)联合环磷酰胺(CTX)治疗对系统性红斑狼疮(SLE)患者病情的影响,以及GnRHa作为CTX治疗的SLE患者卵巢保护剂的安全性。方法选取2013年3月~2014年12月在北京大学深圳医院风湿科确诊为SLE的育龄女性24例,根据是否使用GnRHa分为CTX+GnRHa组和CTX组,每组各12例。采用双能X线骨密度仪检测两组患者腰椎(L1~L4正位)骨密度;比较两组患者治疗前后病情、CTX的累积治疗量、骨密度及治疗后副作用。结果①SLE病情:治疗后两组SLE患者临床症状均消失,两组治疗前后系统性红斑狼疮疾病活动指数(SLEDAI)评分组内比较,差异均有高度统计学意义(t=23.534、19.187,均P=0.000);治疗后两组SLEDAI评分比较,差异有高度统计学意义(t=3.425,P=0.002)。②CTX的累积治疗量:CTX+GnRHa组与CTX组的CTX的累积治疗量分别为(6.9±2.0)、(7.0±1.5)g,两组比较差异无统计学意义(t=0.217,均P=0.830)。③骨密度:两组SLE患者治疗前后腰椎(L1~L4正位)骨密度值比较,差异均无统计学意义(t=0.126、0.175,P=0.901、0.863)。④治疗后的副作用、围绝经期症状及月经改变:CTX+GnRHa组在使用第2次GnRHa后均出现闭经,并伴有不同程度的潮热、多汗、睡眠困难等低雌激素症状,而停用GnRHa、月经恢复后上述症状缓解消失。CTX组有7例出现月经不规则,其中3例月经淋漓不尽,4例月经稀发,但均无低雌激素症状。结论 GnRHa联合CTX治疗对SLE患者的病情无明显的负面影响,GnRHa具有保护CTX治疗中SLE患者卵巢的功能,但其作为CTX治疗的SLE患者的卵巢功能保护剂的安全性及有效性仍有待进一步证实。%Objective To study the effect of gonadotropin releasing hormone analogue (GnRHa) combined with Cy-clophosphamide (CTX) for patients with systemic lupus erythematosus (SLE), and the safety of GnRHa as the

  14. The effect of prolonged gonadotropin-releasing hormone agonist-induced down-regulation on pregnancy outcomes in frozen-thawed embryo transfer cycles for the patients with adenomyosis%促性腺激素释放激素激动剂超长降调节改善子宫腺肌病冻融胚胎移植妊娠结局的作用



    目的 评价促性腺激素释放激素激动剂(GnRH-a)超长垂体降调节对改善子宫腺肌病(AM)冻融胚胎移植(FET)周期妊娠结局的价值. 方法 将AM患者分为GnRH-a+人工周期组和单纯人工周期组,非AM患者行人工周期作为对照组.比较三组患者各项指标包括胚胎种植率、临床妊娠率、流产率、异位妊娠率差异. 结果 GnRH-a+人工周期子宫内膜准备方案明显提高AM患者FET周期胚胎种植率和临床妊娠率,而未增加流产率和异位妊娠率. 结论 GnRH-a超长降调节明显改善AM患者FET妊娠结局.%Objective:To evaluate the effect of prolonged gonadotropin-releasing hormone agonist (GnRH-a)-induced down-regulation on the outcomes of frozen-thawed embryo transfer (FET) cycles in the patients with adenomyosis.Methods:Patients with adenomyosis were divided into GnRH-a plus artificial cycle group (116 cycles) and simple artificial cycle group (106 cycles). Patients without adenomyosis who underwent artificial cycle before FET were grouped as controls (433 cycles). The pregnancy outcomes, including implantation rate, pregnancy rate, abortion rate and ectopic pregnancy rate of three groups were measured and compared.Results: GnRH-a down-regulation plus artificial cycle for endometrial preparation before FET significantly improved the implantation rate and pregnancy rate in adenomyosis patients, with no increase in the abortion rate or ectopic pregnancy rate.Conclusion: Prolonged GnRH-a therapy for down-regulation significantly improve the outcomes of FET cycles in adenomyosis patients.

  15. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...


    ... drug regulations to reflect approval of a new animal drug application (NADA) filed by Pfizer, Inc. The NADA provides for the veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid...-5755, filed NADA 141-322 that provides for the veterinary prescription use of IMPROVEST...

  16. CRC handbook of neurohypophyseal hormone analogs. Volume 2

    Jost, K.; Lebl, M.; Brtnik, F.


    This book is discussed in two parts. The Part 1 discusses the: Prohormones and Hormonogens of Neuro-hypophyseal Hormones, Analogs with Inhibitory properties. Analogs with Dissociated and/or High activities. Introduction. Uterotonic Activity. Galactogogic Activity. Pressor Activity. Antidiuretic Activity. References. Part 2 discusses the Other Important Activities. CNS Activities. Corticotropin- and ..beta..-Entriuretic Action. Natriferic Action. References. Practical Use in Human and Veterinary Medicine. Introduction. Methyloxytocin. Deamino-Oxytocin. Cargutocin. Glypressin. Octapressin. Desmopressin. Analogs Clinically Tried But Not Introduced into Production and Routine Clinical Practice. References. Tables of Analogs and Index.

  17. Institution of combined treatment with testosterone and charcoal-extracted porcine follicular fluid immediately after orchidectomy prevents the postcastration hypersecretion of follicle-stimulating hormone in the hypothalamus-lesioned rhesus monkey (Macaca mulatta) receiving an invariant intravenous gonadotropin-releasing hormone infusion.

    Abeyawardene, S A; Plant, T M


    In the male rhesus monkey, the negative feedback regulation of gonadotropin secretion by the gonad involves a specific inhibitory action of a testicular hormone on FSH release at the level of the anterior pituitary gland. Neither circulating testosterone (T) nor estradiol appears to be able to account for the testicular inhibition of FSH in this species. The purpose of the present study was to begin to examine the role of gonadal peptides in this regard. To this end, an episodic pattern of activity in the pituitary-Leydig cell axis was restored in seven hypothalamus-lesioned male rhesus monkeys with a chronic and unchanging intermittent iv infusion of GnRH (0.1 microgram/min for 3 min every 3 h). This preparation, known as the hypophysiotropic clamp, has been described in detail previously. Charcoal-extracted porcine follicular fluid (pFF) was used as the source of gonadal peptides. In five animals, initiation of combined T replacement and pFF treatment (10-15 ml, sc, every 12 h for 8 days) maintained circulating FSH at concentrations similar to those observed before gonadectomy. Withdrawal of pFF treatment for 8 days while maintaining T replacement resulted in a progressive and dramatic rise in plasma FSH concentrations. Reinitiation of pFF treatment resulted in a return of circulating FSH concentrations toward precastration control values. Changes in LH secretion throughout the experiment were unremarkable. In an attempt to assess any nonspecific effects of porcine protein on gonadotropin secretion, the remaining two animals received charcoal-extracted pig serum instead of pFF. In these animals circulating FSH concentrations rose 7- to 8-fold during the 8 days of combined T replacement and pig serum treatment. These findings provide evidence to support the view that a testicular peptide, most probably inhibin, plays a major role in the negative feedback regulation of gonadotropin secretion in the monkey by exerting an inhibitory action on FSH secretion directly

  18. Adrenocorticotropic hormone analog use for podocytopathies

    Filippone EJ


    Full Text Available Edward J Filippone,1 Shirley J Dopson,2 Denise M Rivers,3 Rebeca D Monk,4 Suneel M Udani,5 Golriz Jafari,6 Solomon C Huang,6 Arafat Melhem,7 Bassim Assioun,7 Paul G Schmitz7 1Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, 2Division of Medicine, Washington Health System, Southwestern Nephrology, Inc, Washington, PA, 3Department of Medicine, University Nephrology, University of Tennessee, Knoxville, TN, 4Department of Medicine, Division of Nephrology, University of Rochester Medical Center, Rochester, NY, 5Department of Medicine, Section of Nephrology, University of Chicago, Chicago, IL, 6Division of Nephrology and Hypertension, Olive View–University of California, Los Angeles Medical Center, Sylmar, CA, 7Department of Internal Medicine, Division of Nephrology, Saint Louis University, St Louis, MO, USABackground: Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS secondary to minimal change disease (MCD or focal segmental glomerulosclerosis (FSGS. We report here our experience with H.P. Acthar® Gel (repository corticotropin injection as first-line or subsequent therapy in patients with INS.Methods: Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted.Results: All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS therapy and all responded (one CR and two PRs. Two of

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

    Kile, J.P.


    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/sup 5//well). Cells treated with GnRH Ca/sup + +/ 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/sup + +/-free media prevented the action of GnRH. GnRH caused a rapid efflux of /sup 45/Ca/sup + +/. Both GnRH-stimulated /sup 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 /sup 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/sub 2/ and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca/sup + +/ does not regulate LH release; (2) GnRH elevates intracellular Ca/sup + +/ by opening both voltage sensitive and receptor mediated Ca/sup + +/ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release.

  20. Acute injection and chronic perfusion of kisspeptin elicit gonadotropins release but fail to trigger ovulation in the mare.

    Decourt, Caroline; Caraty, Alain; Briant, Christine; Guillaume, Daniel; Lomet, Didier; Chesneau, Didier; Lardic, Lionel; Duchamp, Guy; Reigner, Fabrice; Monget, Philippe; Dufourny, Laurence; Beltramo, Massimiliano; Dardente, Hugues


    Kisspeptin has emerged as the most potent gonadotropin-releasing hormone (GnRH) secretagogue and appears to represent the penultimate step in the central control of reproduction. In the sheep, we showed that kisspeptin could be used to manipulate gonadotropin secretion and control ovulation. Prompted by these results, we decided to investigate whether kisspeptin could be used as an ovulation-inducing agent in another photoperiodic domestic mammal, the horse. Equine kisspeptin-10 (eKp10) was administered intravenously as bolus injections or short- to long-term perfusions to Welsh pony mares, either during the anestrus season or at various stages of the cycle during the breeding season. In all the experimental conditions, eKp10 reliably increased peripheral concentrations of both luteinizing hormone and follicle-stimulating hormone. The nature of the response to eKp10 was consistent across experimental conditions and physiological states: the increase in gonadotropins was always rapid and essentially transient even when eKp10 was perfused for prolonged periods. Furthermore, eKp10 consistently failed to induce ovulation in the mare. To gain insights into the underlying mechanisms, we used acute injections or perfusions of GnRH. We also cloned the equine orthologues of the kisspeptin precursor and Kiss1r; this was justified by the facts that the current equine genome assembly predicted an amino acid difference between eKp10 and Kp10 in other species while an equine orthologue for Kiss1r was missing altogether. In light of these findings, potential reasons for the divergence in the response to kisspeptin between ewe and mare are discussed. Our data highlight that kisspeptin is not a universal ovulation-inducing agent.

  1. Thyrotropin-releasing hormone and its analogs accelerate wound healing.

    Nie, Chunlei; Yang, Daping; Liu, Nan; Dong, Deli; Xu, Jin; Zhang, Jiewu


    Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Dual trigger with combination of gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin improve clinical outcomes in PCOS patients undergoing AIH%促性腺激素释放激素激动剂联合小剂量人绒毛膜促性腺激素诱发排卵改善多囊卵巢综合征患者夫精人工授精的临床结局

    汤海瑜; 刘红艳; 高天旸; 全燕; 梁营秋; 任欣; 李瑾; 陈海霞; 王保平; 陈南侨


    Objective To compare the clinical outcomes of using GnRHa alone or combination of GnRHa and hCG to induce follicular maturation in PCOS patients on ovulation induction. Methods Retrospectively analyzed 125 cases of PCOS patients performed AIH, using GnRHa (GnRHa group, 61 cases) alone or combination of GnRHa and hCG (GnRHa+hCG group, 64 cases) to induce follicular maturation, compared the two groups‟ ovulation number, ovulation rate, serum E2 and P levels a week after ovulation, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and the incidence of OHSS and LUFS. Results There were no significant difference in age, duration of infertility, infertility type, BMI, base serum FSH, LH, PRL, E2 and T levels in the two groups. The Gn dosage and days, number of follicles (≥14 mm), serum E2, P level and endometrial thickness differences at HCG day were not statistically significant in two groups except serum LH. The ovulation number, ovulation rate, serum E2 and P levels a week after ovulation, LUF and OHSS incidence in two groups were no significant difference on the rate. There were no significant difference in biochemical pregnancy rate, miscarriage rate, live birth rates in two groups of patients, but GnRHa+hCG group‟s clinical pregnancy rate was significantly higher than GnRHa group (25.0% and 11.5%, respectively, P=0.05). We also found that there were five cases of twin pregnancies in GnRHa+hCG group, but no case of twin pregnancy in GnRHa group. Conclusion Dual trigger with combination of gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin could optimize clinical pregnancy rates in PCOS patients undergoing AIH, and did not increase the risk of OHSS.%目的:比较单独使用促性腺激素释放激素激动剂(GnRHa)与 GnRHa 联合小剂量人绒毛膜促性腺激素(hCG)诱发排卵在多囊卵巢综合征(PCOS)患者促排卵后行夫精人工授精(AIH)的临床

  3. Parathyroid hormone and parathyroid hormone-related protein analogs as therapies for osteoporosis.

    Augustine, Marilyn; Horwitz, Mara J


    Osteoporotic fractures result in significant morbidity and mortality. Anabolic agents reverse the negative skeletal balance that characterizes osteoporosis by stimulating osteoblast-dependent bone formation to a greater degree than osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP) are peptide hormones, which have anabolic actions when administered intermittently. The only FDA-approved anabolic bone agent for the treatment of osteoporosis in the United States is PTH 1-34, or teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog, BA058, have also been shown to increase lumbar spine bone density. These agents and several other PTH and PTHrP analogs, including some which are not administered as injections, continue to be investigated as potential anabolic therapies for osteoporosis.

  4. Correlation between serum inhibin B level afar treatment with gonadotropin releasing hormone agonist and outcome of in vitro fertilization-embryo transfer%促性腺激素释放激素激动剂降调节后血清抑制素B水平对体外受精-胚胎移植结局的预测价值

    林文琴; 杨海燕; 林金菊; 陈霞; 叶碧绿


    Objective To evaluate the decreased level of serum inhibin B(INHB)treated by gunadotropin releasing hormone agonist(GNRH-a)in predicting ovarian response and pregnancy in in vitro fertilization-embryo transfer(IVF-ET).Methods The prospective study enrolled 124 women given by GnRH-a+recombine follicle stimulating hormone(rFSH)+human chorionic gonadotrophin(hCG)long term stimulation protocol undergone their first cycle of IVF-ET treatment.The following predictive factors were collected and analyzed,such as age,basal level of follicle stimulating hormone(FSH),the ratio of FSH/luteinizing hormone(LH),the concentration of INHB after down-regulation,total number of antral follicle count(AFC)and mean ovarian volume. Ovarian response was evaluated by the number of oecytes obtained.A multiple regression analysis and logistic regression model were used for all possible prognostic variables to evaluate the value of difierent hormones in predicting ovariall response and pregnancy after IVF-ET.Receiver operating characteristic(ROC) analysis was used to evaluate the level of INHB in predicting the number of oocytes obtained.The sensitivity and specificity were calculated at the discriminating cut-off point Results The concentration of INHB after down-regulation showed a highly significant positive correlations with the number of oocytes obtained(r=0.435,P0.05).ROC analyses showed INHB after down-regulation had the largest area under curve(AUC)0.933(95%CI:0.878-0.988).When a threshold of 15 ng/L of INHB was established,95.5%sensitivity and 50.0% specificity in ovarian response were observed.Conclusions The level of INHB Was the best factor in predicting ovarian response in IVF-ET.Decreased level of INHB Was the early sign of ovarian reserve function failure,however,useless in predicting IVF-ET outcome.%目的 探讨促性腺激素释放激素激动剂(GnRH-a)降调节后,血清抑制素B(INHB)对体外受精-胚胎移植(IVF-ET)中卵巢反应性和IVF

  5. How to recognize the desensitization of pituitary-ovarian axis achieved by gonadotropin-releasing hormone analogue-induced down-regulation?%识别促性腺激素释放激素激动剂对垂体-卵巢轴降调节抑制程度及意义

    李洁; 刘倍余


    本文通过文献复习讨论促性腺激素释放激素激动剂(GnRH-a)联合促性腺激素(Gn)诱导排卵治疗方案对垂体卵巢轴的降调节作用及意义.广义的降调节作用包括:对血清促性腺激素:卵泡刺激素、黄体生成素(FSH、LH)水平、卵泡周期性发育和类固醇激素合成的影响.临床常见的垂体降调节程度包括过度抑制、部分抑制和未能达到抑制.过度抑制被认为是垂体卵巢轴完全静息状态所需要的,适用于性激素依赖性肿瘤或疾病的治疗.体外受精-胚胎移植(IVF-ET)治疗周期中仅需要达到部分垂体卵巢轴降调节,即保留进入周期募集的卵泡对促性腺激素的反应性和类固醇激素合成.未能达到抑制的垂体卵巢轴伴随着卵泡晚期早发LH峰的风险,与无降调节周期相似.GnRH-a对垂体卵巢轴的降调节作用不仅与其类型、半衰期和患者个体差异有关,并且呈现出剂量与使用时间的依赖性.大部分过度抑制效应的患者可以通过降低GnRH-a剂量逆转,恢复卵巢对外源促性腺激素的反应性.极少数妇女存在降调节的延迟反应,与LH受体变异和受体后缺陷有关.%The review is to discuss how to recognize the desensitization of the pituitary-ovarian axis after gonadotrophin-releasing hormone analogue (GnRH-a) administration, which includes hormone profile, oocytogenesis and steroidogenesis. The original down-regulation is defined as luteinizing hormone (LH) levels <5 U/L, the thickness of endometrium less than 5 mm and follicular diameter

  6. Assessable Value of Nighttime Urine Gonadotropins on Function of Plypothalamic - Pituitary - Gonadal Axis in Children Treated by Gonadotropin- Releasing Hormone Analogue%夜间尿促性腺激素对判断儿童促性腺激素释放激素类似物治疗后下丘脑-垂体-性腺轴功能的价值



    Objective To monitor the adequacy of hypothalamic - pituitary - gonadal axis( HPGA) suppression after receiving gonado tropin -releasing hormone analogue(GnRHa) therapy,tracking gonadotropin (Gn) concentrations in urine by immunochemiluminometric assay (1CMA). Methods Twelve patients who were diagnosed as central precocious puberty(4 patients,all female;age 7. 3 -9. 8 years) or short predicted adult height(8 patients;3 male,5 female;age 8. 8 - 12. 3 years) ,12 h urinary Gn measured by ICMA were performed before the initiation of GnRHa therapy as well as 3 months after the beginning of therapy. Results HPGA suppression was defined as the absence of significant luteinizing hormone( LH)and follicle - stimulating hormone( FSH) responses to GnRH stimulation. LH determinations in urine was significantly lower after therapy compared to before therapy mean LH/Cr[(43.39 ±36.65) IU ? Mol-1 vs (339. 14 ±264.02) IU ? Mol-1, t=3.727,P=0.003],as well as FSH/Cr[(348.20±165.22) IU ? Mol-1 vs (1 841.59 ±1 287.46) IU ? Mol' ,t =3.968, P =0.002]. The sensitivity and specificity of urinary LH determinations ( LH/Cr> 56.44 IU ? Mol-1) to detect inadequate HPGA suppression were 91.7% and 83.3% .respectively. For urinary FSH determinations( FSH/Cr > 604. 97 IU ? Mol-1 ) , the sensitivity and specificity were 93. 8% and 85. 7% , respectively. For urinary FSH determinations (FSH/Cr > 604.97 IU ? Mol-1) and urinary LH determinations( LH/Cr > 56.44 IU ? Mol-1) ,the sensitivity and specificity were 91.7% and 100.0% .respectively. Conclusion Urine measurements of LH and FSH by ICMA, seemed suitable for monitoring HPGA suppression of GnRHa therapy in individual patients.%目的 探讨免疫化学发光法( ICMA)检测夜间12 h尿促性腺激素对判断儿童促性腺激素释放激素类似物(GnRHa)治疗后下丘脑-垂体-性腺轴(HPGA)功能状态的价值.方法 患儿12例,其中中枢性性早熟4例(女,年龄7.3 ~9.8岁),青春期预测终身高矮小8例(男3例,女5

  7. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

    Cortes, D; Thorup, J; Visfeldt, J


    PURPOSE: Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone......, luteinizing hormone and testosterone values are normally low. MATERIALS AND METHODS: We measured the number of spermatogonia per tubule at orchiopexy in 72 consecutive boys with cryptorchidism who underwent simultaneous testicular biopsy. In 19 patients gonadotropin releasing hormone was unsuccessful, while 8...... after surgery alone (p = 0.06). Gonadotropin releasing hormone and HCG influenced germ cells equally. CONCLUSIONS: In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells....

  8. Follicular atresia and infertility in rats treated with a gonadotropin-releasing hormone antagonist.

    Sharpe, K L; Bertero, M C; Lyon, B P; Muse, K N; Vernon, M W


    Adverse effects of the GnRH antagonist Antide on folliculogenesis and fertility were noted when we were evaluating the therapeutic value of Antide on endometriosis in a rat model. Cyclic rats with (n = 56) and without (n = 18) surgically induced endometriosis received Antide (2 mg/kg) or vehicle at noon on days 0 (proestrus), 3, 6, and 9. Rats were killed at noon on days 0, 6, 12, 18, 24, 30, 42, and 165. The number of antral follicles and the number of atretic antral follicles evaluated did not differ (P greater than 0.05) between endometriosis and control rats. Antide-treated rats had more (P less than 0.05 ) atretic antral follicles (64.7%) than vehicle-treated rats (15.3%). Antide-treated rat ovaries contained fewer corpora lutea than those of vehicle-treated rats on days 6, 12, and 18. No corpora lutea were found in Antide-treated rat ovaries after day 18. The abnormal ovarian morphology of the Antide-treated rats persisted for the duration of the project (165 days). Fertility (rats without endometriosis) was assessed by mating vehicle-and Antide-treated rats at spontaneous proestrus (n = 8) for eight posttreatment cycles as well as after follicular stimulation (n = 2). All vehicle-treated and no Antide-treated rats became pregnant. No oocytes were found in the oviducts of Antide-treated rats after eight cycles, indicating that ovulation had not occurred. The serum FSH and estradiol concentrations in the rats treated with Antide were lower (P less than 0.05) on days 6, 12, and 18, but rose to values equal to (days 24 and 30) or greater than (day 42) those in vehicle-treated rats. Serum progesterone levels in rats treated with Antide were lower (P less than 0.05) than those in vehicle-treated rats on all days tested. In conclusion, at a dosage sufficient to suppress reproductive cyclicity (and elicit the regression of endometriosis), Antide also caused long term follicular atresia and infertility.

  9. Prenatal development of gonadotropin-releasing hormone receptors in the rat anterior pituitary

    Jennes, L. (Wright State Univ. School of Medicine, Dayton, OH (USA))


    The development of pituitary GnRH receptors was studied in the rat with in vitro and in vivo autoradiography. GnRH receptors were first seen in pituitary primordia of 13-day-old fetuses. The binding was specific and saturable and was abolished in the presence of 10 microM synthetic GnRH. To examine whether GnRH was available to the fetus, amnionic fluid was collected on days E 12-18. RIA analyses showed that GnRH levels in the amnionic fluid were low on days 12 and 13 (0-20 pM/ml) and rose to 225 pM/ml on day E 16 before they declined to 110 pM/ml on fetal day E 18. The highest levels of GnRH in the amnionic fluid on day E 16 coincided with the first appearance of immunoreactive LH cells, as determined by immunohistochemistry. Intravenous injection of 500 microliters amnionic fluid into pentobarbital-anesthetized adult rats caused a transient 40-60% increase in circulating serum LH in the recipient animal. To show that GnRH from the amnionic fluid has access to the developing pituitary, the 125I-labeled GnRH agonist Buserelin was injected into the amnionic fluid of 13-, 14-, and 15-day-old fetuses in the presence or absence of 10 microM unlabeled GnRH. Autoradiographic analysis of the fetal tissue indicated that the labeled GnRH agonist bound to specific receptors in the primordial pituitaries. The results suggest that the pituitary gonadotropes are differentiated before day E 13 because the expression of GnRH receptors is already an indication of cell determination. Since GnRH is present in the amnionic fluid in a biologically active form and can reach the fetal pituitary, it is concluded that GnRH may be an important factor determining the onset LH synthesis, but not the differentiation, of primordial pituitary cells.

  10. Homologous radioimmunoassay for salmon gonadotropin releasing hormone s-Gn-RH

    Breton, B.; Motin, A. (I.N.R.A., Campus de Beaulieu, 35 - Rennes (France)); Kah, O.; Lemenn, F.; Geoffre, S.; Precigoux, G.; Chambolle, P. (Universite de Bordeaux-I, 33 - Talence (France))


    A radioimmunoassay for Salmon Gn-RH (p-gly-His-Trp-Ser-Tyr-Gly-Trp-Leu-Pro-Gly) (NH/sub 2/) has been developed with a sensitivity of 7 pg/assay tube. The system allows the specific detection of an immunological GnRH related substance in the brain and pituitary of three teleost species but not in an elasmobranch the Dogfish. These results are discussed and some Gn-RH contents of the organs are proposed.

  11. Effective embryo production from Holstein cows treated with gonadotropin-releasing hormone during early lactation.

    Ogata, Yasuhiro; Yu, Guang-Min; Hidaka, Takemasa; Matzushige, Tadami; Maeda, Teruo


    The low efficiency of embryo production in Holstein cows during early lactation presents many challenges for animal production. To improve its efficiency, the outcomes of single GnRH injections 48 hours before each of three cycles of ovum pick up (OPU; weeks 2, 4, and 6) were compared with three cycles of unstimulated OPU (controls; weeks 1, 3, and 5) in 35 Holstein cows during 6 weeks of early lactation (40-80 days postpartum). More total follicle numbers (19.5 vs. 16.0; P controls (15.3 vs. 11.5; P controls (2.8 vs. 1.7 and 5.8 vs. 4.2, respectively; P control cycles (13.7 vs. 9.6; P controls (9.0 vs. 6.2 two-cell embryos; 4.7 vs. 3.0 four-cell embryos; 3.3 vs. 2.0 morulae; and 3.0 vs. 1.7 blastocysts, respectively). Moreover, there was no significant difference in pregnancy rate of the recipient cows after embryo transfer (57.1% vs. 42.1%; P > 0.05) no matter if the embryos came from the GnRH-treated cycles or not. Thus, GnRH-stimulated OPUs improved the efficiency of embryo production in Holstein cows during early lactation. This novel method for in vitro embryo production should benefit the dairy industry.

  12. Tritium labeling of gonadotropin releasing hormone in its proline and histidine residues

    Klauschenz, E.; Bienert, M.; Egler, H.; Pleiss, U.; Niedrich, H.; Nikolics, K.

    3,4-dehydroproline9-GnRH prepared by solid phase peptide synthesis was tritiated catalytically under various conditions yielding 3H-GnRH with specific radioactivities in the range from 35-60 Ci/mmol and full LH releasing activity in vitro. Using palladium/alumina catalyst, the tritiation of the double bond occurs within ten minutes. Investigation of the tritium distribution between the amino acid residues showed a remarkably high incorporation of tritium into the histidine residue (11 to 37%). On the basis of this observation, the tritium labeling of GnRH and angiotensin I by direct catalytic hydrogen-tritium exchange was found to be useful for the labeling of these peptides at remarkably high specific radioactivity.

  13. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    Annamaria Morelli


    Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.

  14. Gonadotropin-Releasing Hormone Agonist Treatment in Postmenopausal Women with Hyperandrogenism of Ovarian Origin

    Vollaard, Esther S.; van Beek, Andre P.; Verburg, Frederik A. J.; Roos, Annemieke; Land, Jolande A.


    Context: The most frequent cause of virilization in postmenopausal women is excessive androgen production of ovarian origin. Bilateral oophorectomy is usually performed, even in cases of benign tumors or hyperthecosis. This is the first report of a case series of long-term GnRH-agonist treatment of

  15. Dopamine regulation of gonadotropin-releasing hormone neuron excitability in male and female mice.

    Liu, Xinhuai; Herbison, Allan E


    Numerous in vivo studies have shown that dopamine is involved in the regulation of LH secretion in mammals. However, the mechanisms through which this occurs are not known. In this study, we used green fluorescent protein-tagged GnRH neurons to examine whether and how dopamine may modulate the activity of adult GnRH neurons in the mouse. Bath-applied dopamine (10-80 μm) potently inhibited the firing of approximately 50% of GnRH neurons. This resulted from direct postsynaptic inhibitory actions through D1-like, D2-like, or both receptors. Further, one third of GnRH neurons exhibited an increase in their basal firing rate after administration of SCH23390 (D1-like antagonist) and/or raclopride (D2-like antagonist) indicating tonic inhibition by endogenous dopamine in the brain slice. The role of dopamine in presynaptic modulation of the anteroventral periventricular nucleus (AVPV) γ-aminobutyric acid/glutamate input to GnRH neurons was examined. Exogenous dopamine was found to presynaptically inhibit AVPV-evoked γ-aminobutyric acid /glutamate postsynaptic currents in about 50% of GnRH neurons. These effects were, again, mediated by both D1- and D2-like receptors. Neither postsynaptic nor presynaptic actions of dopamine were found to be different between diestrous, proestrous, and estrous females, or males. Approximately 20% of GnRH neurons were shown to receive a dopaminergic input from AVPV neurons in male and female mice. Together, these observations show that dopamine is one of the most potent inhibitors of GnRH neuron excitability and that this is achieved through complex pre- and postsynaptic actions that each involve D1- and D2-like receptor activation.

  16. Gonadotropin-releasing Hormone Agonists, Orchiectomy, and Risk of Cardiovascular Disease

    Thomsen, Frederik Birkebæk; Sandin, Fredrik; Garmo, Hans


    : To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias. DESIGN, SETTING, AND PARTICIPANTS: Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992-1999 in the Prostate...... with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed. RESULTS AND LIMITATIONS: The risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0...... found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer....

  17. Parathyroid Hormone-Related Protein Analogs as Osteoporosis Therapies.

    Esbrit, Pedro; Herrera, Sabina; Portal-Núñez, Sergio; Nogués, Xavier; Díez-Pérez, Adolfo


    The only bone anabolic agent currently available for osteoporosis treatment is parathyroid hormone (PTH)-either its N-terminal 1-34 fragment or the whole molecule of 1-84 aminoacids-whose intermittent administration stimulates new bone formation by targeting osteoblastogenesis and osteoblast survival. PTH-related protein (PTHrP) is an abundant factor in bone which shows N-terminal homology with PTH and thus exhibits high affinity for the same PTH type 1 receptor in osteoblasts. Therefore, it is not surprising that intermittently administered N-terminal PTHrP peptides induce bone anabolism in animals and humans. Furthermore, the C-terminal region of PTHrP also elicits osteogenic features in vitro in osteoblastic cells and in various animal models of osteoporosis. In this review, we discuss the current concepts about the cellular and molecular mechanisms whereby PTHrP may induce anabolic actions in bone. Pre-clinical studies and clinical data using N-terminal PTHrP analogs are also summarized, pointing to PTHrP as a promising alternative to current bone anabolic therapies.

  18. Direct regulation of gonadotropin release by neurokinin B in tilapia (Oreochromis niloticus).

    Biran, Jakob; Golan, Matan; Mizrahi, Naama; Ogawa, Satoshi; Parhar, Ishwar S; Levavi-Sivan, Berta


    Neurokinin B (NKB) was recently identified as a key regulator of reproduction in mammals and fish. Fish were found to possess a specific novel neurokinin termed NKF. To study the role of NKB/NKF in the regulation of fish reproduction and to investigate the role of NKB/NKF and their receptors in the piscine pituitary, we have identified the NKB/tachikinin 3 receptor (tac3r) system in tilapia. Bioinformatics and phylogenetic analyses have demonstrated that the tilapia holds 1 putative tac3 gene and 2 NKB receptor genes (tac3ra and tac3rb) that clustered with other piscine Tac3 and NKB receptor lineages. Furthermore, we found that in African cichlids, NKB peptides differ from other vertebrate NKBs in their C-terminal sequence, possessing isoleucine instead of valine as the X in the NKB FXGLM-NH2-terminal consensus sequence. Signal transduction analysis demonstrated that tilapia NKB (tiNKB), tiNKF, and human NKB activated both CRE-luc and SRE-luc transcriptional activity of both tilapia and human NKB receptors. Two hours after ip injection of tiNKB, the plasma levels of both FSH and LH were increased, whereas tiNKF was more effective in increasing LH levels. However, tiNKB was more effective than tiNKF in increasing both FSH and LH from tilapia pituitary dispersed cells. Using in situ hybridization and fluorescent immunohistochemistry, we have shown that LH cells possess tac3, tac3ra, and tac3rb mRNAs, whereas FSH cells possess mainly tac3rb and tac3ra and tac3 to a much lesser extent. These results suggest that the members of the NKB/tac3r system may serve as paracrine/autocrine regulators of gonadotropin release in fish pituitary.

  19. Glucocorticoid regulation of gonadotropin release from gonadotropes of ovine pituitary gland in vitro

    Nangalama, A.W.


    In order to understand the role of glucocorticoids in the regulation of gonadotropin release by the pituitary gland, the short-term effects of cortisol perifusion (1.5 h to 8 hrs) on GnRH-induced LH secretion were investigated. To determine the biochemical mechanism(s) by which cortisol can act to modulate GnRH-induced LH release, the interactions of cortisol and arachidonic acid in GnRH-stimulated LH release were examined. Cortisol perifusion for 1.5 hr had no effect on GnRH-induced LH release, but longer treatment periods (4 hr-8 hrs) significantly reduced GnRH-stimulated LH release (4.0 hr, p < 0.01; 6.0 hr, p < 0.001; 8.0 hr, p < 0.01). Treatment and animal effects were highly significant (p < 0.001). There were significant interactions (p < 0.001) between treatment and animal as determined by a two-way ANOVA. Cortisol treatment also produced progressive increases in basal LH secretion with time (1.5 hr, p < 0.05; 4.0 hr, p < 0.01; 6.0 hr, p < 0.01; 8.0 hr, p < 0.001). Incubation of pituitary tissue with arachidonic acid (AA) resulted in a linear dose-response of LH (p < 0.001). Cortisol infusion failed to inhibit GnRH-induced LH release in which 10{sup {minus}4}M AA was administered for 20 min before a 10 min, 10{sup {minus}10}M GnRH pulse. Like cortisol, chloroquine also failed to inhibit AA-induced LH release. Perifusion with 10{sup {minus}6}M cortisol for 6.0 hours significantly (p < 0.001) blocked GnRH-stimulated (H{sup 3})AA release 24% below the basal (100%) ({sup 3}H)AA secretion. Reduction of ({sup 3}H)AA release was accompanied by decreased GnRH-stimulated LH secretion.

  20. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone.

    Pasquino, A M; Pucarelli, I; Segni, M; Matrunola, M; Cerroni, F; Cerrone, F


    GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 microg/kg im every 21 days, for at least 2-3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg x week s.c., 6 days weekly, for 2-4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 in GnRHa plus GH vs. 13.0 +/- 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 +/- 1.3 vs. 152.7 +/- 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs. 155.5 +/- 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 +/- 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2-3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.

  1. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

    Cortes, Dina; Thorup, Jørgen Mogens; Visfeldt, J


    Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing...... hormone and testosterone values are normally low....

  2. Effect of atrial natriuretic peptide on gonadotropin release in superfused rat pituitary cells.

    Horvath, J; Ertl, T.; Schally, A V


    Cardiac atrial muscle cells produce a polypeptide hormone that plays a role in the control of water and electrolyte balance and blood pressure. The circulating form of this hormone is the atrial natriuretic peptide (ANP), which contains 28 amino acids. Various immunohistochemical studies have shown that ANP is present in many areas of the central nervous system, including the median eminence. In our studies, we investigated the effect of ANP in a superfused rat pituitary cell system. When ANP...

  3. Gonadotrofina coriônica humana e hormônio liberador de gonadotrofina como indutores da reprodução do jundiá - DOI: 10.4025/actascianimsci.v30i3.929 Human chorionic gonadotropin and gonadotropin-releasing hormone as breeding inducers of jundiá - DOI: 10.4025/actascianimsci.v30i3.929

    Paulo César Falanghe Carneiro


    Full Text Available Este trabalho foi realizado com o objetivo de avaliar parâmetros reprodutivos de machos e fêmeas de jundiá adultos após a aplicação do HCG (gonadotrofina coriônica humana e do GnRHa (hormônio liberador do hormônio gonadotrópico e compará-los àqueles obtidos quando usado o extrato hipofisário da carpa comum. Etapa 1 (Machos - quatro grupos, com oito machos cada, receberam os seguintes tratamentos: M1: sem hormônio; M2: extrato hipofisário 0,5 mg kg-1; M3: HCG 200 UI kg-1; M4: GnRHa+inibidor dopaminergético 0,1 glóbulo(Ovopel® kg-1. Etapa 2 (fêmeas – 36 fêmeas foram divididas em cinco grupos: F1: extrato hipofisário em duas aplicações, 0,5 e 5,0 mg kg-1; F2: HCG em duas aplicações, 200 e 400 UI kg-1; F3: HCG 400 UI kg-1 em dose única; F4: HCG 1000 UI kg-1 em dose única; F5: GnRHa+inibidor dopaminergético 1 glóbulo(Ovopel® kg-1. O uso do extrato hipofisário da carpa comum aumentou significativamente o volume de sêmen liberado e estimulou maior quantidade de fêmeas à liberar óvulos. O HCG e o GnRHa não apresentaram resultados positivos no tocante à reprodução induzida do jundiá, nas doses utilizadas neste estudo.Hormone acquisition represents high cost, justifying the importance of studies searching for better results on inducing fish reproduction in laboratory conditions. This study analyzed the efficiency of HCG and GnRHa for gonad maturation and gamete production in jundiá, and compare the results to those using pituitary extract. Stage 1 (Males - Four groups with eight males each received the following treatments: M1: Without hormone; M2: Pituitary extract 0.5 mg/kg; M3: HCG 200 UI/kg; M4: GnRHa+dopamine receptor antagonist 0.1 pellet/kg. Stage 2 (Females – Thirty six females were separated in 5 groups: F1: Pituitary extract in two applications, 0.5 and 5.0 mg/kg; F2: HCG in two applications, 200 and 400 UI/kg; F3: HCG 400 UI/kg in a single dose; F4: HCG 1000 UI/kg in a single dose; F5: Gn

  4. In utero and lactational exposure to PCB 118 and PCB 153 alter ovarian follicular dynamics and GnRH-induced luteinizing hormone secretion in female lambs

    Kraugerud, Marianne; Aleksandersen, Mona; Nyengaard, Jens Randel;


    The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes received corn oil, PCB 118, or PCB 153, and offspring was maintained until...... 60 days postpartum. Ovarian follicles were quantified using stereology. Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured using radioimmunoassay before and after administration of a gonadotropin releasing hormone (GnRH) analog. PCB 118 exposure increased numbers...... of transitional, secondary, and the sum of secondary, early antral, and antral (Σsecondary-antral) follicles, PCB 153 exposure only increased the number of primary follicles. GnRH-induced LH levels were significantly elevated in the PCB 153 exposure group. We conclude that PCB 153 and PCB 118 alter follicular...

  5. Value of Urinary Gonadotropin Determinations during Gonadotropin-Releasing Hormone Analog Stimulation Testing in Children%尿促性腺激素检查在儿童促性腺激素释放激素类似物激发试验中的价值

    王喜平; 徐庄剑; 马亚萍; 张文杰; 庞兴甫; 王勍


    目的 探讨尿促性腺激素(UGn)检查在儿童促性腺激素释放激素类似物(GnRHa)激发试验中的临床价值.方法 50例生长或发育异常患儿住院行GnRHa激发试验,收集注射曲普瑞林后连续5个分段尿(首段1.5 h,其余各段为1.0 h),应用免疫化学发光分析法检测黄体生成素(LH)和卵泡刺激素(FSH)水平.结果 1.分段UGh峰值:3.5 h时限内尿LH(ULH)含量峰值、ULH/肌酐(cr)的峰值指标分别与血LH峰值(PLH)的相关系数(r)以及ULH含量峰值/UFSHs(与ULH峰值同标本的FSH)指标与血PLH/FSH峰值(PFSH)的r值分别为0.852、0.774和0.899,4.5 h时限内上述相应指标的r值分别为0.836、0.774和0.894:3.5 h时限内此三指标诊断下丘脑-垂体-性腺轴(HPGA)启动的受试者工作特性(ROC)曲线下面积分别为0.960、0.923和0.907,4.5 h时限内的曲线下面积分别为0.952、0.928和0.905.除2.5 h时限内IJLH/Cr的峰值与血PLH的r值(0.809)、5.5 h时限内的ULH含量峰值/UFSHs与血PLH/PFSH的r值(0.904)外,2.5 h和5.5 h时限内的所有上述相应指标值均不高于3.5 h和4.5 h 2个时限内相应指标的高值.2.各时段(分段的和)UGn:2.5 h、3.5 h,4.5 h和5.5 h时段UIM水平分别与血PLH的r值为0.815、0.842、0.852和0.814,其诊断HPGA启动的ROC曲线下面积分别为0.913、0.944、0.958和0.923;上述相应时段ULH/Cr分别与血PLH的r值为0.802、0.831、0.844和0.814,其诊断HPGA启动的ROC曲线下面积分别为0.911、0.940、0.955和0.919.3.血自发性促性腺激素(Gn):血自发性LH(SLH)与血PLH的r值为0.603,血SLH/自发性FSH(SFSH)与血PLH/PFSH的r值为0.566,SLH和SLH/SFSH诊断HPGA启动的ROC曲线下面积分别为0.792和0.675.4.诊断HPGA启动的灵敏度和特异度:当4.5 h时限内ULH/Cr峰值和4.5 h时段ULH含量的截断值(Youden指数最高时)分别≥492.581 8 IU·Mol-1和≥0.289 3 IU·L-1时,其灵敏度分别为96.3%和92.6%,特异度均为91.3%.结论 在GnRHa激发试验中ICIVIA检测的UGn价值优于血自发性Gn.

  6. Development of neuropeptide analogs capable of traversing the integument: A case study using diapause hormone analogs in Helicoverpa zea.

    Zhang, Qirui; Nachman, Ronald J; Kaczmarek, Krzysztof; Kierus, Krzysztof; Zabrocki, Janusz; Denlinger, David L


    Diapause hormone and its analogs terminate pupal diapause in Helicoverpa zea when injected, but if such agents are to be used as effective diapause disruptors it will be essential to develop simple techniques for administering active compounds that can exert their effect by penetrating the insect epidermis. In the current study, we used two molecules previously shown to have high diapause-terminating activity as lead molecules to rationally design and synthesize new amphiphilic compounds with modified hydrophobic components. An assay for diapause termination identified 13 active compounds with EC50's ranging from 0.9 to 46.0 pmol per pupa. Three compounds, Decyl-1963, Dodecyl-1967, and Heptyl-1965, selected from the 13 compounds most active in breaking diapause following injection, also successfully prevented newly-formed pupae from entering diapause when applied topically. These compounds feature straight-chain, aliphatic hydrocarbons from 7 to 12 carbons in length; DH analogs with either a short-chain length of 4 or an aromatic phenethyl group failed to act topically. Compared to a high diapause incidence of 80-90% in controls, diapause incidence in pupae receiving a 10 nmole topical application of Decyl-1963, Dodecyl-1967, or Heptyl-1965 dropped to 30-45%. Decyl-1963 and Dodecyl-1967 also remained effective when topically applied at the 1 nmole level. These results suggest the feasibility of developing DH agonists that can be applied topically and suggest the identity of new lead molecules for development of additional topically-active DH analogs. The ability to penetrate the insect epidermis and/or midgut lining is critical if such agents are to be considered for future use as pest management tools.

  7. Use of a gonadotropin releasing hormone agonist implant as an alternative for surgical castration in male ferrets (Mustela putorius furo).

    Schoemaker, N J; van Deijk, R; Muijlaert, B; Kik, M J L; Kuijten, A M; de Jong, F H; Trigg, T E; Kruitwagen, C L J J; Mol, J A


    Surgical castration in ferrets has been implicated as an etiological factor in the development of hyperadrenocorticism in this species due to a castration-related increase in plasma gonadotropins. In search for a suitable alternative, the effect of treatment with the depot GnRH-agonist implant, deslorelin, on plasma testosterone concentrations and concurrent testes size, spermatogenesis, and the typical musky odor of intact male ferrets was investigated. Twenty-one male ferrets, equally divided into three groups, were either surgically castrated, received a slow release deslorelin implant or received a placebo implant. Plasma FSH and testosterone concentrations, testis size and spermatogenesis were all suppressed after the use of the deslorelin implant. The musky odor in the ferrets which had received a deslorelin implant was less compared to the ferrets which were either surgically castrated or had received a placebo implant. These results indicate that the deslorelin implant effectively prevents reproduction and the musky odor of intact male ferrets and is therefore considered a suitable alternative for surgical castration in these animals.

  8. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Qi-Hong Sun


    Conclusions: Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females.

  9. Identification of a novel pituitary-specific chicken gonadotropin-releasing hormone receptor and its splice variants.

    Shimizu, Mamiko; Bédécarrats, Grégoy Y


    In all vertebrates, GnRH regulates gonadotropin secretion through binding to a specific receptor on the surface of pituitary gonadotropes. At least two forms of GnRH exist within a single species, and several corresponding GnRH receptors (GNRHRs) have been isolated with one form being pituitary specific. In chickens, only one type of widely expressed GNRHR has previously been identified. The objectives of this study were to isolate a chicken pituitary-specific GNRHR and to determine its expression pattern during a reproductive cycle. Using a combined strategy of PCR and rapid amplification of cDNA ends (RACE), a new GNRHR (chicken GNRHR2) and two splice variants were isolated in domestic fowl (Gallus gallus domesticus). Full-length GNRHR2 and one of its splice variant mRNAs were expressed exclusively in the pituitary, whereas mRNA of the other splice variant was expressed in most brain tissues examined. The deduced amino acid sequence of full-length chicken GNRHR2 reveals a seven transmembrane domain protein with 57%-65% homology to nonmammalian GNRHRs. Semiquantitative real-time PCR revealed that mRNA levels of full-length chicken GNRHR2 in the pituitary correlate with the reproductive status of birds, with maximum levels observed during the peak of lay and 4 wk postphotostimulation in females and males, respectively. Furthermore, GnRH stimulation of GH3 cells that were transiently transfected with cDNA that encodes chicken GNRHR2 resulted in a significant increase in inositol phosphate accumulation. In conclusion, we isolated a novel GNRHR and its splice variants in chickens, and spatial and temporal gene expression patterns suggest that this receptor plays an important role in the regulation of reproduction.

  10. The fetal hypothalamus has the potential to generate cells with a gonadotropin releasing hormone (GnRH phenotype.

    Roberto Salvi

    Full Text Available BACKGROUND: Neurospheres (NS are colonies of neural stem and precursor cells capable of differentiating into the central nervous system (CNS cell lineages upon appropriate culture conditions: neurons, and glial cells. NS were originally derived from the embryonic and adult mouse striatum subventricular zone. More recently, experimental evidence substantiated the isolation of NS from almost any region of the CNS, including the hypothalamus. METHODOLOGY/FINDINGS: Here we report a protocol that enables to generate large quantities of NS from both fetal and adult rat hypothalami. We found that either FGF-2 or EGF were capable of inducing NS formation from fetal hypothalamic cultures, but that only FGF-2 is effective in the adult cultures. The hypothalamic-derived NS are capable of differentiating into neurons and glial cells and most notably, as demonstrated by immunocytochemical detection with a specific anti-GnRH antibody, the fetal cultures contain cells that exhibit a GnRH phenotype upon differentiation. CONCLUSIONS/SIGNIFICANCE: This in vitro model should be useful to study the molecular mechanisms involved in GnRH neuronal differentiation.

  11. 17β-estradiol regulation of T-type calcium channels in gonadotropin-releasing hormone neurons

    Zhang, Chunguang; Bosch, Martha A.; Rick, Elizabeth A.; Kelly, Martin J.; Ronnekleiv, Oline K.


    T-type calcium channels are responsible for generating low-threshold spikes that facilitate burst firing and neurotransmitter release in neurons. GnRH neurons exhibit burst firing, but the underlying conductances are not known. Previously, we have found that 17β-estradiol (E2) increases T-type channel expression and excitability of hypothalamic arcuate nucleus neurons. Therefore, we used ovariectomized oil- or E2-treated EGFP-GnRH mice to explore the expression and E2-regulation of T-type channels in GnRH neurons. Based on single cell RT-PCR and real-time PCR quantification of the T-type channel α1-subunits, we found that all three subunits were expressed in GnRH neurons with Cav3.3≥Cav3.2>Cav3.1. The mRNA expression of the three subunits was increased with surge-inducing levels of E2 during the morning. During the afternoon, Cav3.3 mRNA expression remained elevated, whereas Cav3.1 and Cav3.2 were decreased. The membrane estrogen receptor agonist STX increased the expression of Cav3.3, but not Cav3.2 in GnRH neurons. Whole-cell patch recordings in GnRH neurons revealed that E2 treatment significantly augmented T-type current density at both time-points, and increased the rebound excitation during the afternoon. Although E2 regulated the mRNA expression of all three subunits in GnRH neurons, the increased expression combined with the slower inactivation kinetics of the T-type current indicates that Cav3.3 may be the most important for bursting activity associated with the GnRH/LH surge. The E2-induced increase in mRNA expression, which depends in part on membrane-initiated signaling, leads to increased channel function and neuronal excitability, and could be a mechanism by which E2 facilitates burst firing and cyclic GnRH neurosecretion. PMID:19710308

  12. Psychosocial stress inhibits amplitude of gonadotropin-releasing hormone pulses independent of cortisol action on the type II glucocorticoid receptor.

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Tilbrook, Alan J; Karsch, Fred J


    Our laboratory has developed a paradigm of psychosocial stress (sequential layering of isolation, blindfold, and predator cues) that robustly elevates cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This decrease in LH pulse amplitude is due, at least in part, to a reduction in pituitary responsiveness to GnRH, caused by cortisol acting via the type II glucocorticoid receptor (GR). The first experiment of the current study aimed to determine whether this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared with nonstressed ovariectomized ewes. The second experiment tested if this stress-induced decrease in GnRH pulse amplitude is mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated to three groups: nonstress control, stress, and stress plus the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared with nonstress controls. Importantly, the stress also lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol action via the type II GR was antagonized. Therefore, we conclude that psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol action on the type II GR. The present findings, combined with our recent observations, suggest that the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different.

  13. Insight into the neuroendocrine site and cellular mechanism by which cortisol suppresses pituitary responsiveness to gonadotropin-releasing hormone.

    Breen, Kellie M; Davis, Tracy L; Doro, Lisa C; Nett, Terry M; Oakley, Amy E; Padmanabhan, Vasantha; Rispoli, Louisa A; Wagenmaker, Elizabeth R; Karsch, Fred J


    Stress-like elevations in plasma glucocorticoids rapidly inhibit pulsatile LH secretion in ovariectomized sheep by reducing pituitary responsiveness to GnRH. This effect can be blocked by a nonspecific antagonist of the type II glucocorticoid receptor (GR) RU486. A series of experiments was conducted to strengthen the evidence for a mediatory role of the type II GR and to investigate the neuroendocrine site and cellular mechanism underlying this inhibitory effect of cortisol. First, we demonstrated that a specific agonist of the type II GR, dexamethasone, mimics the suppressive action of cortisol on pituitary responsiveness to GnRH pulses in ovariectomized ewes. This effect, which became evident within 30 min, documents mediation via the type II GR. We next determined that exposure of cultured ovine pituitary cells to cortisol reduced the LH response to pulse-like delivery of GnRH by 50% within 30 min, indicating a pituitary site of action. Finally, we tested the hypothesis that suppression of pituitary responsiveness to GnRH in ovariectomized ewes is due to reduced tissue concentrations of GnRH receptor. Although cortisol blunted the amplitude of GnRH-induced LH pulses within 1-2 h, the amount of GnRH receptor mRNA or protein was not affected over this time frame. Collectively, these observations provide evidence that cortisol acts via the type II GR within the pituitary gland to elicit a rapid decrease in responsiveness to GnRH, independent of changes in expression of the GnRH receptor.

  14. Neurobiological study of fish brains gives insights into the nature of Gonadotropin-releasing hormone 1-3 neurons.

    Tomomi eKarigo


    Full Text Available Accumulating evidence suggests that up to three different molecular species of GnRH peptides encoded by different paralogs of gnrh genes are expressed by anatomically distinct groups of GnRH neurons in the brain of one vertebrate species. They are called gnrh1, gnrh2, and gnrh3. Recent evidence from molecular, anatomical, and physiological experiments strongly suggests that each GnRH system functions differently. Here, we review recent advancement in the functional studies of the three different GnRH neuron systems, mainly focusing on the electrophysiological analysis of the GnRH-green fluorescent protein (GFP transgenic animals. The introduction of GFP transgenic animals for the electrophysiological analysis of GnRH neurons greatly advanced our knowledge on their anatomy and electrophysiology, especially of gnrh1 neurons, which has long defied detailed electrophysiological analysis of single neurons because of their small size and scattered distribution. Based on the results of recent studies, we propose that different electrophysiological properties, especially the spontaneous patterns of electrical activities and their time-dependent changes, and the axonal projections characterize the different functions of GnRH1-3 neurons; GnRH1 neurons act as hypophysiotropic neuroendocrine regulators, and GnRH2 and GnRH3 neurons act as neuromodulators in wide areas of the brain.

  15. Potential of a gonadotropin-releasing hormone vaccine to suppress musth in captive male Asian elephants (Elephas maximus)

    Somgird, Chaleamchat; Homkong, Pongpon; Sripiboon, Supaphen; Brown, Janine L; Stout, Tom A E; Colenbrander, Ben; Mahasawangkul, Sittidet; Thitaram, Chatchote


    Musth in adult bull elephants is a period of increased androgen concentrations ranging from a few weeks to several months. For captive elephant bull management, musth presents a serious challenge because of the aggressive behavior of musth bulls toward people and other elephants. Commercially availa

  16. Triggering ovulation with gonadotropin-releasing hormone agonist versus human chorionic gonadotropin in polycystic ovarian syndrome. A randomized trial

    Amr Hassaan Farag


    Full Text Available Objectives: To compare GnRH agonist to hCG for triggering ovulation in polycystic ovarian syndrome treated with clomiphene citrate. Study design: Prospective randomized study. Materials & methods: Eighty five infertile women with PCOS participated in a randomized allocation concealed prospective trial and had induction of ovulation with clomiphene citrate. GnRH agonist 0.2 mg subcutaneously (group 1 or hCG 10,000 IU intramuscularly (group 2 was given to trigger ovulation. Primary outcome was mid-luteal serum progesterone, while secondary outcomes were ovulation rates and clinical pregnancy rates along 3 cycles. Results: No difference was found between group 1 and group 2 regarding mean serum progesterone and clinical pregnancy rates in each cycle. Cumulative pregnancy rates were similar (17.14% versus 20% respectively; P = 0.332. Ovulation rates were 80% versus 68.6% (P = 0.413; 94.3% versus 90.9% (P = 0.669; 97.1% versus 93.7% (P = 0.603 in the two groups respectively. However, a significant rise in number of patients with mid-luteal serum progesterone >10 ng/mL was noted in the 3rd cycle between both groups, (P < 0.0001 for group 1 while P = 0.007 for group 2. Conclusion: Triggering ovulation with GnRH-a after treatment with clomiphene citrate in PCOS, in view of its known protective effect against OHSS, may be an effective physiological alternative to conventional hCG without compromising luteal function and pregnancy rates after repeated cycles of treatment.

  17. Early pregnancy loss in women stimulated with gonadotropin-releasing hormone antagonist protocols according to oral contraceptive pill pretreatment.

    Bellver, José; Albert, Carmen; Labarta, Elena; Pellicer, Antonio


    To evaluate and compare the risk of early pregnancy loss in patients stimulated with GnRH antagonist protocols according to oral contraceptive pill (OCP) pretreatment. Retrospective case-control study. Instituto Valenciano de Infertilidad. University of Valencia. Spain. One thousand five hundred thirty-nine patients, aged <36, stimulated with GnRH antagonists for IVF between January 1, 2000 and November 1, 2005. Reproductive outcome was compared based on the application (or not) of OCP pretreatment: 944 women were included in the OCP group and 595 in the non-OCP group. The Student's t test was used for statistics. Pregnancy, biochemical pregnancy, ectopic pregnancy, early clinical pregnancy loss, early pregnancy loss, and ongoing pregnancy rates. No significant differences were observed in any of the outcome parameters. Early pregnancy loss rates were similar: 23% in the OCP pretreatment group versus 19.2% in the non-OCP pretreatment group. However, longer periods of ovarian stimulation and higher doses of gonadotropins needed to be employed in the OCP group. There is not sufficient evidence to confirm OCP pretreatment as a risk factor for miscarriage in patients stimulated with GnRH antagonist protocols.

  18. Treatment of lactating dairy cows with gonadotropin-releasing hormone before first insemination during summer heat stress.

    Voelz, B E; Rocha, L; Scortegagna, F; Stevenson, J S; Mendonça, L G D


    The objectives of the experiments were to compare ovarian responses, pregnancy per artificial insemination, and pattern of insemination of 2 estrus detection-based presynchronization protocols before first artificial insemination (AI) during heat stress. In experiment 1, primiparous lactating dairy cows (n=1,358) from 3 dairies were assigned randomly to 2 treatments at 60±3 (±SD) DIM (study d 0): (1) treatment with 100 µg of GnRH on study d 0 (Gpresynch), or (2) no treatment on study d 0 (control). In experiment 2, multiparous lactating dairy cows (n=1,971) from 3 dairies were assigned randomly to 2 treatments at 49±3 (±SD) DIM (study d 0), similar to experiment 1. In both experiments, PGF2α injections were administered 14 d apart starting on study d 7 for all cows. Cows not inseminated after detection of estrus were submitted to a timed artificial insemination protocol at study d 35. In a subgroup of cows from 2 dairies, concentrations of progesterone were determined from blood samples collected on study d 0 and 7. Furthermore, ovaries were examined by ultrasonography on study d -14, 0, and 7 to determine cyclic status and ovulation in response to GnRH treatment. In experiment 1, progesterone concentration was not different on d 0, but progesterone was increased for Gpresynch compared with control cows on study d 7 (3.6±0.3 vs. 2.7±0.4 ng/mL), respectively. Ovulation risk from study d 0 to 7 was increased for Gpresynch compared with control (50.6 vs. 15.2%). Control cows were inseminated at a faster rate than Gpresynch cows [adjusted hazard ratio (AHR)=0.89, 95% confidence interval=0.80 to 1.00], and the interaction between treatment and dairy affected pregnancy per artificial insemination at 36 and 94 d post-artificial insemination. In experiment 2, concentrations of progesterone did not differ on study d 0 or 7, despite ovulation risk from study d 0 to 7 being greater in Gpresynch than control cows (46.9 vs. 23.8%). The interaction between treatment and dairy affected hazard of insemination with Gpresynch cows from dairy 1 (AHR=1.21; 1.05 to 1.41) being inseminated faster than control cows. Hazard of pregnancy was affected by treatment because Gpresynch cows became pregnant at a faster rate than control cows (AHR=1.25; 1.04 to 1.50). In conclusion, GnRH-based presynchronization protocols initiated before the end of the voluntary waiting period may have benefits in reproductive efficiency of estrus detection-based programs during heat stress. In addition, treatment with GnRH decreased the prevalence of anovular cows at the initiation of PGF2α injections.

  19. Luteal phase supplementation after gonadotropin-releasing hormone agonist trigger in fresh embryo transfer: the American versus European approaches.

    Humaidan, Peter; Engmann, Lawrence; Benadiva, Claudio


    The challenges in attaining an adequate luteal phase after GnRH agonist (GnRHa) trigger to induce final oocyte maturation have resulted in different approaches focused on rescuing the luteal phase insufficiency so that a fresh transfer can be carried out without jeopardizing IVF outcomes. Over the years, two different concepts have emerged: intensive luteal support with aggressive exogenous administration of E2 and P; and low-dose hCG rescue in the form of a small dose of hCG either on the day of oocyte retrieva or on the day of GnRHa trigger (the so called "dual trigger"). Both approaches have been shown to be effective in achieving pregnancy rates similar to those obtained after conventional hCG trigger and resulting in a very low risk of ovarian hyperstimulation syndrome (OHSS). Although the idea of freezing all embryos after GnRHa trigger and transferring them in a subsequent frozen-thawed cycle has been gaining momentum, a fresh transfer leading to the live birth of a healthy child is currently considered to be the goal of IVF treatment. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Is the effect of premature elevated progesterone augmented by human chorionic gonadotropin versus gonadotropin-releasing hormone agonist trigger?

    Connell, Matthew T; Patounakis, George; Healy, Mae Wu; DeCherney, Alan H; Devine, Kate; Widra, Eric; Levy, Michael J; Hill, Micah J


    To compare the effect of P on live birth rate between hCG and GnRH agonist (GnRH-a) trigger cycles. Retrospective cohort study. Large private assisted reproductive technology (ART) practice. A total of 3,326 fresh autologous ART cycles. None. Live birth. A total of 647 GnRH-a trigger cycles were compared with 2,679 hCG trigger cycles. Live birth was negatively associated with P in both the hCG trigger (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52-0.76) and the agonist trigger cohorts (OR 0.56, 95% CI 0.45-0.69). Interaction testing evaluating P and trigger medication was not significant, indicating that P had a similar negative effect on live birth rates in both cohorts. Progesterone ≥2 ng/mL occurred more commonly in GnRH-a trigger cycles compared with hCG trigger cycles (5.5% vs. 3.1%) and was negatively associated with live birth in both the hCG trigger (OR 0.28, 95% CI 0.11-0.73) and agonist trigger cohorts (OR 0.35, 95% CI 0.14-0.90). When P ≥2 ng/mL, the live birth rates were poor and similar in the hCG and GnRH-a cohorts (5.9% vs. 14.2%), indicating that P ≥2 ng/mL had a similar negative effect on live birth in both cohorts. Elevated serum P on the day of hCG was negatively associated with live birth rates in both hCG and GnRH-a trigger cycles. Published by Elsevier Inc.


    SUFang-Ming; LUXiang-Yun; GONGYue-Ting


    A potent D-Trp6-GnRH iodinated by the lactoperoxidase glucose oxidase method was used as a ligand to bind specifically to the rat ovarian membrane, The ovariu GnRH receptor has a binding affinity with the agonist similar to that of the pituiary receptor, Ka

  2. Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol.

    Park, Chan Woo; Hwang, Yu Im; Koo, Hwa Seon; Kang, Inn Soo; Yang, Kwang Moon; Song, In Ok


    To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.

  3. Response to gonadotropin-releasing hormone challenge: Seasonal variation in steroid production in a viviparous lizard, Tiliqua nigrolutea.

    Edwards, Ashley; Jones, Susan M


    The hypothalamic-pituitary-gonadal axis plays a central role in the regulation of gamete maturation, sex steroid production and the stimulation of reproductive behaviours in vertebrates. In seasonal breeders, the timely activation and deactivation of this control system is important to ensure successful reproduction: this process is not well understood in species which breed irregularly. Males of the viviparous blotched blue-tongued lizard, Tiliqua nigrolutea, breed annually, while females display a multiennial cycle. We investigated seasonal variation in hypothalamic-pituitary-gonadal axis responsiveness in both sexes of T. nigrolutea. We measured changes in plasma concentrations of testosterone and estrogen in response to a single intraperitoneal injection of a GnRH agonist, chicken-II LH-RH, at three reproductively distinct times of year. Plasma testosterone concentrations in males were significantly increased during gonadal quiescence, but not initial or final spermatogenesis. There was no estrogen response in males at any time of year. Conversely, in females, there was an increase in plasma testosterone, but not estrogen, concentration, in reproductively quiescent females several months in advance of a successful pregnancy. These results indicate clear variation in HPG axis activity with sex, season and reproductive condition in this seasonally breeding viviparous lizard. This study opens the way for further investigation into the mechanisms by which internal (body condition) and external seasonal cues (temperature and photoperiod) are coordinated to regulate reproduction in irregularly-breeding reptiles.

  4. Localisation of gonadotropin releasing hormone (GRH) in the forebrain and neurohypophysis of the trout (salmo gairdneri). An immunofluorescence study.

    Goos, H J; Murathanoglu, O


    The double antibody immunofluorescence technique was applied to serial coronal and sagittal sections of the brains of the trout, Salmo gairdneri, using an antibody against mammalian LH-RH. Immunoreactive material was found in small perikarya, situated at both sides of the ventriculus communis in the area dorsalis pars medialis of the telencephalon. The axons of these perikarya, also containing immunoreactive material, do not form a tract, but run diffusely in a caudo-ventral direction towards the pituitary stalk. The ending of these fibres has not yet been established.

  5. Structure-Function Relations of Strigolactone Analogs: Activity as Plant Hormones and Plant Interactions

    Maja Cohen; Cristina Prandi; Ernesto G. Occhiato; Silvia Tabasso; Smadar Wininger; Nathalie Resnick; Yosef Steinberger


    Strigolactones (SLs) have several functions as signaling molecules in their interactions with symbiotic arbuscular mycorrhizal (AM) fungi and the parasitic weeds Orobanche and Striga.SLs are also a new class of plant hormone regulating plant development.In all three organisms,a specific and sensitive receptor-mediated perception system is suggested.By comparing the activity of synthetic SL analogs on Arabidopsis root-hair elongation,Orobanche aegyptiaca seed germination,and hyphal branching of the AM fungus Glomus intraradices,we found that each of the tested organisms differs in its response to the various examined synthetic SL analogs.Structure-function relations of the SL analogs suggest substitutions on the A-ring as the cause of this variation.Moreover,the description of competitive antagonistic analogs suggests that the A-ring of SL can affect not only affinity to the receptor,but also the molecule's ability to activate it.The results support the conclusion that Arabidopsis,Orobanche,and AM fungi possess variations in receptor sensitivity to SL analogs,probably due to variation in SL receptors among the different species.

  6. Vibrational spectroscopic studies of solid recombinant bovine growth hormone and related growth hormone analogs

    Thamann, Thomas J.; Chao, Robert S.


    Infrared and Raman spectra have been obtained for lyophilized recombinant bovine growth hormone (r-bGH), partially reduced, and completely reduced r-bGH, plus a tryptic digest fragment of r-bGH. Amide I and II data indicate r-bGH to have substantial helical character. Partially reduced r-bGH, in which the carboxyl terminal disulfide bridge (residues 181, 189) has been cleaved, has slightly less helical content than r-bGH. The spectral data indicate that breaking the carboxyl terminal cystine link produces only localized structural alterations. The additional cleavage of the second disulfide bridge (residues 53 164) leads to a further decrease in helix content, accompanied by increases in β-sheet and disordered structures. A tryptic digest r-bGH fragment (residues 96-133), which contains a small amount of biological activity (≈10%), has predominantly helical structure.

  7. Behavioral Effects of Org 2766, a Synthetic Analog of the Adrenocorticotrophic Hormone (4-9), in 14 Outpatient Autistic Children.

    Buitelaar, Jan K.; And Others


    Fourteen autistic children (ages 5-13) were administered Org 2766 (a synthetic analog of the adrenocorticotrophic hormone 4-9) or a placebo for 4 weeks. The hormone appeared to decrease stereotypic behavior and increase such behaviors as "change toys,""locomote," and "talk," though Aberrant Behavior Checklist ratings did not show significant…

  8. The views of young adults and their parents on hormone treatment for short stature in adolescence

    Visser-van Balen, Hanneke; Geenen, Rinie; Looij, Janneke; Huisman, Jaap; Wit, Jan M.; Sinnema, Gerben


    Aim: To examine the view of young adults and their parents on growth hormone (GH) and gonadotropin-releasing hormone agonist (GnRHa) treatment in adolescence for idiopathic short stature (ISS) or short stature born small for gestational age (SGA). Methods: Thirty young adults with ISS or SGA (18 tre

  9. The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro

    L.J. Hofland (Leo); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven); A. Beckers (Albert); J. van der Hoek (Joost); P.M. van Koetsveld (Peter); W.W. de Herder (Wouter); M. Waaijers (Marlijn); D. Sprij-Mooij (Diana); C. Bruns (Christian); G. Weckbecker (Gisbert); R.A. Feelders (Richard)


    textabstractTo determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenom

  10. Conformational origin of a difficult coupling in a human growth hormone releasing factor analog.

    Deber, C M; Lutek, M K; Heimer, E P; Felix, A M


    During the solid-phase synthesis of the human growth hormone releasing factor (GRF) analog [Ala15, Leu27, Asn28] -GRF(1-32)-OH, incorporation of Boc-Gln16 was determined to be incomplete. While aggregation of growing resin-bound peptide chains with concomitant beta-sheet formation and "precipitation" has been proposed to account in general for such "difficult coupling," no feature of sequence in the Gln16 region of this GRF analog provided an immediate rationale for this result. We now report 500 MHz 1H NMR spectra of a series of resin-bound GRF segments surrounding the Gln16 position (19-32 through 14-32), swelled in dimethylsulfoxide-d6 solutions [GRF(14-32) = Leu14-Ala-Gln-Leu-Ser(Bzl)-Ala-Arg(Tos)-Lys(CIZ)-Leu- Leu-Gln-Asp(OcHex)-Ile-Leu-Asn-Arg(Tos)-Gln-Gln-Gly32-PAM resin]. While relatively sharp spectra are observed for GRF(19-32), components with resonances broadened by an order-of-magnitude appear in spectra of the 18-32 and 17-32 peptide-resin, and the entire spectrum of 16-32 is ill-resolved and highly broadened. Subsequent spectra sharpen again (15-32, 14-32). These combined synthesis/spectroscopic experimental results, in conjunction with predictive analyses using standard Chou-Fasman 2 degrees structure parameters, suggest that the completeness of the Gln16 coupling is hindered by formation of a specific, folded beta-sheet/beta-turn structure in GRF(16-32) (with the turn located at 18-21, "upstream" of the difficult coupling site), and accompanying aggregation of peptide chains. This analysis suggests that awareness of such potential beta-sheet/beta-turn sequences can guide analog choices, and/or facilitate pre-programming of synthesis steps in anticipation of problem couplings.

  11. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly.

    Potorac, Iulia; Petrossians, Patrick; Daly, Adrian F; Alexopoulou, Orsalia; Borot, Sophie; Sahnoun-Fathallah, Mona; Castinetti, Frederic; Devuyst, France; Jaffrain-Rea, Marie-Lise; Briet, Claire; Luca, Florina; Lapoirie, Marion; Zoicas, Flavius; Simoneau, Isabelle; Diallo, Alpha M; Muhammad, Ammar; Kelestimur, Fahrettin; Nazzari, Elena; Centeno, Rogelio Garcia; Webb, Susan M; Nunes, Marie-Laure; Hana, Vaclav; Pascal-Vigneron, Véronique; Ilovayskaya, Irena; Nasybullina, Farida; Achir, Samia; Ferone, Diego; Neggers, Sebastian J C M M; Delemer, Brigitte; Petit, Jean-Michel; Schöfl, Christof; Raverot, Gerald; Goichot, Bernard; Rodien, Patrice; Corvilain, Bernard; Brue, Thierry; Schillo, Franck; Tshibanda, Luaba; Maiter, Dominique; Bonneville, Jean-François; Beckers, Albert


    GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly. © 2016 Society for Endocrinology.

  12. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

    Wang JW


    Full Text Available Ji-wen Wang,1,2 Ying Li,3 Zhi-gang Mao,1,2 Bin Hu,1,2 Xiao-bing Jiang,1,2 Bing-bing Song,4 Xin Wang,4 Yong-hong Zhu,4 Hai-jun Wang1,21Department of Neurosurgery and Pituitary Tumor Center, The First Affiliated Hospital, Sun Yat-sen University, 2Key Laboratory of Pituitary Adenoma in Guangdong Province, 3State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 4Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of ChinaAbstract: Excessive growth hormone (GH is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs and GH receptor antagonist; the former consists of lanreotide Autogel (ATG and octreotide long-acting release (LAR, and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated

  13. Feedback effects of estradiol and progesterone on ovulation and fertility of dairy cows after gonadotropin-releasing hormone-induced release of luteinizing hormone.

    Stevenson, J S; Pulley, S L


    An experiment was conducted with the objective to determine the effects of estradiol, progesterone, presence of a corpus luteum (CL), and size of a dominant follicle on the characteristics and patterns of GnRH-induced LH release and subsequent ovulation during a timed artificial insemination (TAI) program, or a combination of these. In 70 lactating dairy cows, a total of 163 blood collection periods resulting in a GnRH-induced LH release were analyzed. Concentrations of LH were measured in hourly samples (0 through 6 h after GnRH) during each of the blood collection periods, whereas concentrations of progesterone and estradiol were measured in the sample before GnRH treatment (0 h). Measures of LH included time to LH peak concentration during the 6-h blood collection period, the 2 largest concentrations of LH, mean, and variance of the 6 LH concentrations under each LH curve. Individual and combination effects of CL presence and a dominant follicle ≤ or >13.5mm, in addition to individual and combination effects of progesterone: low (release during 6 h after each of 163 injections. Measures of GnRH-induced LH concentration were inhibited at greater concentrations of progesterone and in the presence of a CL. In contrast, GnRH-induced LH concentrations were increased when estradiol was ≥4.0 pg/mL, but relatively unaffected by the size of the dominant follicle. Furthermore, resulting incidences of ovulation were decreased at greater progesterone concentrations and presence of a CL, and increased at greater estradiol concentrations and presence of follicles >13.5mm. In cows with or without a CL, the presence of a follicle >13.5mm did not increase mean LH concentration or incidence of ovulation. We conclude that when progesterone concentration exceeded 0.5 ng/mL at the time of GnRH treatment, subsequent LH concentrations and ovulation were suppressed. At that same concentration of progesterone or when concentrations of estradiol were ≥4 pg/mL, TAI pregnancy outcomes were improved in the face of similar incidences of ovulation suggesting greater progesterone or lesser estradiol at the time of AI may inhibit pregnancy establishment by other mechanisms.

  14. Interactions between Two Different G Protein-Coupled Receptors in Reproductive Hormone-Producing Cells: The Role of PACAP and Its Receptor PAC1R

    Haruhiko Kanasaki; Aki Oride; Tomomi Hara; Tselmeg Mijiddorj; Unurjargal Sukhbaatar; Satoru Kyo


    Gonadotropin-releasing hormone (GnRH) and gonadotropins are indispensable hormones for maintaining female reproductive functions. In a similar manner to other endocrine hormones, GnRH and gonadotropins are controlled by their principle regulators. Although it has been previously established that GnRH regulates the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—both gonadotropins—from pituitary gonadotrophs, it has recently become clear that hypothal...

  15. Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

    Wang, Ji-wen; Li, Ying; Mao, Zhi-gang; Hu, Bin; Jiang, Xiao-bing; Song, Bing-bing; Wang, Xin; Zhu, Yong-hong; Wang, Hai-jun


    Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits. PMID:24421637

  16. Effects of juvenile hormone analogs and 20-hydroxyecdysone on diapause termination in eggs of Locusta migratoria and Oxya yezoensis.

    Kidokoro, Kurako; Iwata, Ken-Ichi; Fujiwara, Yoshihiro; Takeda, Makio


    To understand the hormonal control of embryonic diapause, juvenile hormone analogs (JHAs), methoprene and hydroprene, and 20-hydroxyecdysone (20E) were applied onto diapause eggs of Locusta migratoria and Oxya yezoensis. These insects enter diapause at the mid-stage of embryogenesis prior to blastokinesis. Topical application of JHAs significantly facilitated diapause termination in both species but JHA-treated embryos underwent abnormal morphogenesis, pigmentation and sclerotization without dorsal closure. The Locusta eggs immersed in the 20E solution for 24h terminated diapause in a dose-dependent manner. We also investigated phosphorylation of extracellular signal-regulated kinase (ERK), a member of mitogen-activated protein kinase (MAPK), during diapause-terminating process of Locusta migratoria and found that ERK was activated either by cold exposure or JHA treatment. The possible involvement of the hormones and ERK in embryonic diapause and the possibility of ecdysteroids synthesis by prothoracic glands of diapause embryo were proposed.

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

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


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

  18. Recent advancements in the hormonal stimulation of ovulation in swine

    Knox RV


    Full Text Available Robert V Knox Department of Animal Sciences, 360 Animal Sciences Laboratory, University of Illinois, Champaign Urbana, IL, USA Abstract: Induction of ovulation for controlled breeding is available for use around the world, and conditions for practical application appear promising. Many of the hormones available, such as human chorionic gonadotropin (hCG, gonadotropin-releasing hormone (GnRH and its analogs, as well as porcine luteinizing hormone (pLH, have been shown to be effective for advancing or synchronizing ovulation in gilts and weaned sows. Each of the hormones has unique attributes with respect to the physiology of its actions, how it is administered, its efficacy, and approval for use. The timing for induction of ovulation during the follicle phase is critical as follicle maturity changes over time, and the success of the response is determined by the stage of follicle development. Female fertility is also a primary factor affecting the success of ovulation induction and fixed time insemination protocols. Approximately 80%–90% of female pigs will develop mature follicles following weaning in sows and synchronization of estrus in gilts. However, those gilts and sows with follicles that are less developed and mature, or those that develop with abnormalities, will not respond to an ovulatory surge of LH. To address this problem, some protocols induce follicle development in all females, which can improve the overall reliability of the ovulation response. Control of ovulation is practical for use with fixed time artificial insemination and should prove highly advantageous for low-dose and single-service artificial insemination and for use with frozen-thawed and sex-sorted sperm. Keywords: artificial insemination, follicle, hormone, ovulation, swine

  19. Effects of ionizing radiation and pretreatment with (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

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


    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.

  20. Efficacy of exogenous hormone (GnRHa) for induced breeding of climbing perch Anabas testudineus (Bloch, 1792) and influence of operational sex ratio on spawning success.

    Mandal, Babita; Kumar, Rajesh; Jayasankar, P


    The climbing perch, Anabas testudineus, is an air-breathing fish having great consumer preference as a food fish and is considered a prime candidate species for aquaculture. Spawning success is an important issue while using hormones for captive induced breeding. In the first experiment, a trial was conducted to assess the efficacy of a synthetic Gonadotropin Releasing Hormone analog (sGnRHa) on the spawning success of climbing perch. Female fish were administered six different doses each with a single intramuscular injection of sGnRHa hormone at 0.002 (TOD1), 0.005 (TOD2), 0.01 (TOD3), 0.015 (TOD4), 0.02 (TOD5), 0.03 (TOD6) μg/g body weight. Similarly, males were administered half of the hormone dose of females in all the respective treatment groups. The greatest (Phormone dose of 0.015μg/g body weight and a female-male ratio of 1:2 are optimal for enhanced spawning success in the climbing perch.

  1. Pyriproxyfen, a juvenoid hormone analog, does not induce male production in parthenogenetic lineages of Eucypris virens (Crustacea: Ostracoda

    Francesc MEZQUITA


    Full Text Available Analogs of juvenoid hormones are increasingly recommended for controlling insect pests in agriculture. One of these analogs, pyriproxyfen, was found to be very potent in inducing male production in Daphnia under laboratory conditions, even after acute exposure. Other studies also demonstrated a major role of juvenoid hormones for the sex determination in arthropods that have sex chromosomes. We exposed parthenogenetic lineages of the freshwater ostracod Eucypris virens to a wide range of pyriproxyfen concentrations, and compared mortality and fecundity between treated and control animals. Animals exposed to the highest concentrations of pyriproxyfen (3-30 nM experienced a higher mortality than control animals, but no treatment effects were found on the production rates of eggs and hatchlings. Also, hatchlings that emerged from eggs deposited by treated individuals did not suffer from an increased mortality rate. No males were found among the 91 hatchlings that could be grown to adulthood. These results suggest that previous observations of a reduced population growth of ostracods in treated field crops might not be due to an alteration of the sex ratio, but rather to an increased mortality of the exposed females.

  2. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats

    Schally, A.V.; Paz-Bouza, J.I.; Schlosser, J.V.; Karashima, T.; Debeljuk, L.; Gandle, B.; Sampson, M.


    Possible protective effects of the agonist (D-Trp/sup 6/)LH-RH and antagonist N-Ac(D-Phe(pCl)/sup 1,2/,D-Trp/sup 3/,D-Arg/sup 6/,D-Ala/sup 10/)LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group give 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist (D-Trp/sup 6/)LH-RH. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist (D-Trp/sup 6/)LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

  3. Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin. Live birth after frozen-thawed embryo replacement cycles

    Griesinger, Georg; Kolibianakis, E M; Papanikolaou, E G


    . PATIENT(S): Patients under observation previously had been recruited into two concurrently performed, independent, randomized controlled trials (comparing hCG with GnRH-agonist for triggering final oocyte maturation in GnRH-antagonist multiple-dose protocols in normal responder patients) encompassing...

  4. Effects of prostaglandin F2 alpha and a gonadotropin-releasing hormone agonist on inositol phospholipid metabolism in isolated rat corpora lutea of various ages

    Lahav, M.; West, L.A.; Davis, J.S.


    The sensitivity of rat corpora lutea to luteolytic agents increases with luteal age. We examined the effect of prostaglandin F2 alpha (PGF2 alpha) and (D-Ala6,Des-Gly10)GnRH ethylamide (GnRHa) on inositol phospholipid metabolism in day 2 and day 7 corpora lutea from PMSG-treated rats. Isolated corpora lutea were incubated with 32PO4 or (3H)inositol and were treated with LH, PGF2 alpha, or GnRHa. Phospholipids were purified by TLC, and the water-soluble products of phospholipase-C activity (inositol phosphates) were isolated by ion exchange chromatography. In day 2 corpora lutea, PGF2 alpha, (10 microM) and GnRHa (100 ng/ml) significantly increased 32PO4 incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI), but not into other fractions. LH provoked slight increases in PA. Results were similar with 30 min of prelabeling or simultaneous addition of 32PO4 and stimulants. In other experiments, PGF2 alpha and GnRHa provoked rapid increases (1-5 min) in the accumulation of inositol mono-, bis-, and trisphosphates. LH did not significantly increase inositol phosphate accumulation, but stimulated cAMP accumulation in 2-day-old corpora lutea. Inositol phospholipid metabolism was increased in day 7 corpora lutea compared to that in day 2 corpora lutea. This increase was associated with increased incorporation of 32PO4 into PA and PI and increased accumulation of (3H)inositol phosphates. In day 7 corpora lutea, which are very sensitive to the luteolytic effect of PGF2 alpha, the PG-induced increase in PA labeling was small and inconsistent, whereas PI labeling was unaffected in 30-min incubations. GnRHa was without effect in such corpora lutea. LH, PGF2 alpha, or GnRHa did not increase inositol phosphate accumulation in 7-day-old corpora lutea. These studies demonstrate that the transformation of young (day 2) to mature (day 7) corpora lutea is associated with an increase in luteal inositol phospholipid metabolism.

  5. Schistocephalus solidus infections increase gonadotropins and gonadotropin releasing hormone (GnRH3) mRNA levels in the three-spined stickleback, Gasterosteus aculeatus.

    Shao, Yi Ta; Tseng, Yung Che; Trombley, Susanne; Hwang, Pung Pung; Schmitz, Monika; Borg, Bertil


    Parasites often impair the reproduction of their hosts, one well known case being the cestode Schistocephalus solidus which is a common parasite in three-spined sticklebacks, Gasterosteus aculeatus. One of the possible ways that this could be exerted is by suppression on the brain-pituitary-gonadal (BPG) axis. In this study, mRNA levels of FSH-β and LH-β and of GnRH2 (cGnRH II) and GnRH3 (sGnRH) were measured via Q-PCR in infected and uninfected fish sampled from the field a few weeks before the onset of breeding. The pituitary mRNA levels of both FSH-β and LH-β were higher in infected males than in uninfected males. Also in females, FSH-β mRNA levels were higher in infected individuals than in others, whereas there was no significant difference found in LH-β expression. Brain mRNA levels of GnRH3 were higher in infected fish than in uninfected fish in both sexes, but no difference was found in GnRH2 mRNA levels. Thus, infection by S. solidus was able to alter the expressions not only of gonadotropins (GtHs), but also of GnRH which has not been observed previously. However, the effects are opposite to what should be expected if the parasite suppressed reproduction via actions on the brain-pituitary level. The gonads are perhaps more likely to be impaired by the parasites in other ways, and changed feedbacks on the BPG axis could then lead to the increases in GtHs and GnRH.

  6. Function and Gene Expression of Gonadotropin-releasing Hormone%促性腺激素释放激素及其基因表达调控

    吴旭; 陈宽维; 王金玉; 严美姣



  7. Comparing stimulation requirements and final outcome between early follicular and mid luteal pituitary suppression in the long gonadotropin releasing hormone agonist protocol.

    Sarhan, Abdulmagid; Harira, Mervat; Elshazly, Sherine; Nouh, Ahmad


    To compare stimulation requirements and ICSI outcome when agonist treatment is started in the early follicular phase or in mid luteal phase of the cycle. 181 infertile patients were randomly assigned to: group A (N=66) and group B (N=115). GnRH-a (Triptorelin) subcutaneous daily injections started on day 20-22 of the previous cycle till pituitary suppression is achieved where gonadotropins stimulation commenced. In group A, agonist treatment was started on the first or second days of the cycle, in group B it was started on day 20-22 of the cycle. The agonist treatment was continued till the day of (hCG) administration. The stimulation requirements were similar in the two groups. The days of t agonist treatment required to reach pituitary suppression were higher in group A: 12.5±6.4 than in group B, 11±4.5. Days of stimulation (10.4±1.7 and 10.3±1.6) and number of gonadotropin vials (40.1±8.7and 39.3±9.5) did not differ between both groups. The mean number of oocytes retrieved, mean number of embryos produced (11.7±7.4 and 13.3±9.3) (5.9±4.2and 6±5.2) were similar in both groups. The rates of fertilization and cleavage were similar in the two groups. Pregnancy rates were similar in both groups. The clinical pregnancy rates per cycle was 31.8% and 33%, while pregnancy rates per embryo transfer was 36.2 % and 36.5% in groups A and B respectively. Starting pituitary suppression with GnRH agonist in the early follicular phase or mid luteal phase were comparable regarding stimulation requirements and final outcomes.

  8. Short versus Long Gonadotropin-Releasing Hormone Analogue Suppression Protocols in IVF/ICSI Cycles in Patients of Various Age Ranges.

    Jianping Ou

    Full Text Available To compare the two GnRH-a protocols (long GnRH-a protocol and short GnRH-a protocol for ovarian stimulation in IVF/ICSI cycles in patients of various age ranges.A total of 5662 IVF-ET/ICSI cycles from 2010 to 2013 were retrospectively identified. The cycles were divided into two groups: a long protocol group and short protocol group. In each group, the patients were divided into four age ranges: 40 years. The duration of stimulation, total dose of Gn, implantation rate and pregnancy rate were compared.The total dose of Gn was significantly higher, and the duration of stimulation was significantly longer, in the long protocol group than in the short protocol group for all age ranges (P<0.05. If the patients were of the same age range, the number of oocytes retrieved, MII oocytes, and high-quality embryos in the long protocol group were all significantly greater than those in the short protocol group (P<0.05. In the long protocol group, the clinical pregnancy rates of the four age ranges were 52.76%, 44.33%, 36.15% and 13.33%, respectively, which were significantly higher than those in the short protocol group (33.33%, 24.58%, 22.49% and 8.72%, respectively; P<0.05. The same trend was also found in the implantation rates of the four age ranges. As the age increased, the clinical pregnancy and implantation rates, as well as the number of oocytes retrieved, MII oocytes, and high-quality embryos, of the long protocol group significantly decreased (P<0.05.Our study demonstrated that regardless of patient age, the long protocol was superior to the short protocol in terms of the number of retrieved oocytes, as well as the implantation and pregnancy rates.

  9. Kisspeptin increases gamma-aminobutyric acidergic and glutamatergic transmission directly to gonadotropin-releasing hormone neurons in an estradiol-dependent manner.

    Pielecka-Fortuna, Justyna; Moenter, Suzanne M


    GnRH neurons are the final central pathway controlling fertility. Kisspeptin potently activates GnRH release via G protein-coupled receptor 54 (GPR54). GnRH neurons express GPR54, and kisspeptin can act directly; however, GPR54 is broadly expressed, suggesting indirect actions are possible. Transsynaptic mechanisms are involved in estradiol-induced potentiation of GnRH neuron response to kisspeptin. To investigate these mechanisms, separate whole-cell voltage-clamp recordings were performed of gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission to GnRH neurons in brain slices before and during kisspeptin treatment. To determine whether estradiol alters the effect of kisspeptin on synaptic transmission, mice were ovariectomized and either left with no further treatment (OVX) or treated with estradiol implants (OVX+E). Cells were first studied in the morning when estradiol exerts negative feedback. Kisspeptin increased frequency and amplitude of GABAergic postsynaptic currents (PSCs) in GnRH neurons from OVX+E mice. Blocking action potentials eliminated the effect on frequency, indicating presynaptic actions. Amplitude changes were due to postsynaptic actions. Kisspeptin also increased frequency of glutamatergic excitatory PSCs in cells from OVX+E animals. Kisspeptin did not affect either GABAergic or glutamatergic transmission to GnRH neurons in cells from OVX mice, indicating effects on transmission are estradiol dependent. In contrast to stimulatory effects on GABAergic PSC frequency during negative feedback, kisspeptin had no effect during positive feedback. These data suggest estradiol enables kisspeptin-mediated increases in GABA and glutamate transmission to GnRH neurons. Furthermore, the occlusion of the response during positive feedback implies one consequence of estradiol positive feedback is an increase in transmission to GnRH neurons mediated by endogenous kisspeptin.

  10. Molecular Cloning, Genomic Organization and Developmental Regulation of a Novel Receptor from Drosophila melanogaster Structurally Related to Gonadotropin-Releasing Hormone Receptors from Vertebrates

    Hauser, Frank; Søndergaard, Leif; Grimmelikhuijzen, Cornelis J.P.


    RH) receptors from vertebrates. Using the polymerase chain reaction, withDrosophilacDNA as a template, and oligonucleotide probes coding for the presumed exons of this gene, we were able to clone the cDNA coding for this receptor. The transmembrane region of the receptor shows 36% amino acid residue identity...

  11. γ-Aminobutyric Acid B Receptor Mediated Inhibition of Gonadotropin-Releasing Hormone Neurons Is Suppressed by Kisspeptin-G Protein-Coupled Receptor 54 Signaling

    Zhang, Chunguang; Bosch, Martha A.; Rønnekleiv, Oline K.; Kelly, Martin J.


    γ-Aminobutyric acid (GABA) is one of the most important neurotransmitters that regulate the excitability of GnRH neurons. Numerous studies have shown that GABA activates Cl− currents in GnRH neurons, and these effects are antagonized by GABAA receptor antagonists. The GABAB receptor is a heterodimer composed of GABAB R1 and R2, and although both subunits have been localized in GnRH neurons, nothing is known about the cellular signaling of this Gαi,o-coupled receptor in GnRH neurons. Using whole-cell recordings from mouse enhanced green fluorescent protein-GnRH neurons, we found that the GABAB receptor agonist baclofen hyperpolarized GnRH neurons through activation of an inwardly rectifying K+ current in a concentration-dependent manner. The effects of baclofen were antagonized by the selective GABAB receptor antagonist CGP 52432 with a Ki (inhibitory constant) of 85 nm. Furthermore, in the presence of the GABAA receptor antagonist picrotoxin, GABA hyperpolarized GnRH neurons in a similar manner. Treatment with 17β-estradiol as compared with oil vehicle did not significantly alter either the EC50 for the baclofen-induced response (0.8 ± 0.1 vs. 1.0 ± 0.1 μm, respectively) or the maximal outward current (10.8 ± 1.7 pA vs. 11.4 ± 0.6 pA, respectively) in GnRH neurons. However, the outward current (and membrane hyperpolarization) was abrogated by submaximal concentrations of the G protein-coupled receptor 54 (GPR54) agonist kisspeptin-10 in both groups, indicating that Gαq-coupled (GPR54) can desensitize the GABAB receptor-mediated response. Therefore, the activation of GABAB receptors in GnRH neurons may provide increased inhibitory tone during estrogen-negative feedback states that is attenuated by kisspeptin during positive feedback. PMID:19164470

  12. Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer

    Ulmert, David; Vickers, Andrew J; Scher, Howard I


    The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase...... of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon(®)), a novel GnRH antagonist....

  13. Comparison of gene expression profiles in granulosa and cumulus cells after ovulation induction with either human chorionic gonadotropin or a gonadotropin-releasing hormone agonist trigger

    Borgbo, Tanni; Povlsen, Betina Boel; Andersen, Claus Yding


    To explore differences in follicle transcriptomes in patients having oocyte maturation with either a bolus of hCG or GnRHa.......To explore differences in follicle transcriptomes in patients having oocyte maturation with either a bolus of hCG or GnRHa....

  14. Comparison of two different starting multiple dose gonadotropin-releasing hormone antagonist protocols in a selected group of in vitro fertilization-embryo transfer patients.

    Escudero, Ernesto; Bosch, Ernesto; Crespo, Juana; Simón, Carlos; Remohí, José; Pellicer, Antonio


    To compare the efficacy of two starting protocols of multiple dose GnRH antagonists (GnRH-a). Prospective randomized controlled study. In vitro fertilization-embryo transfer program at the Instituto Valenciano de Infertilidad, Valencia, Spain. One hundred nine patients undergoing controlled ovarian hyperstimulation (COH) with recombinant gonadotropins and GnRH-a (0.25 mg/d). Patients started GnRH-a administration on stimulation day 6 (group 1) or when the leading follicle reached a mean diameter of 14 mm (group 2). Implantation and pregnancy rates; serum E(2) and LH levels during ovarian stimulation; days of stimulation and GnRH-a administration. Days needed for ovarian stimulation were similar in both groups but there was a significant difference when comparing days of GnRH-a administration. Serum E(2) and LH followed similar curves in both groups. Implantation and pregnancy rates were 23.7% and 44.4 % in group 1 and 28.6% and 50.9 % in group 2 (P=not significant [NS]). The efficacy of the two starting protocols of the multiple dose GnRH-a evaluated in this study is similar; however, this remark can only be drawn for a selected group of patients.

  15. Conditional Viral Tract Tracing Delineates the Projections of the Distinct Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in the Mouse.

    Yip, Siew Hoong; Boehm, Ulrich; Herbison, Allan E; Campbell, Rebecca E


    Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection patterns of kisspeptin neurons originating from either the rostral periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus (ARN) using a cell-specific, viral-mediated tract-tracing approach. We stereotaxically injected a Cre-dependent recombinant adenovirus encoding farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers from ARN kisspeptin neurons projected widely; however, we did not find any evidence for direct contact with GnRH neuron somata or proximal dendrites in either sex. In contrast, we identified RP3V kisspeptin fibers in close contact with GnRH neuron somata and dendrites in both sexes. Fibers originating from both the RP3V and ARN were observed in close contact with distal GnRH neuron processes in the ARN and in the lateral and internal aspects of the median eminence. Furthermore, GnRH nerve terminals were found in close contact with the proximal dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were found contacting RP3V kisspeptin neurons in both sexes. Together these data delineate selective zones of kisspeptin neuron inputs to GnRH neurons and demonstrate complex interconnections between the distinct kisspeptin populations and GnRH neurons.

  16. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders.

    Griffin, Daniel; Benadiva, Claudio; Kummer, Nicole; Budinetz, Tara; Nulsen, John; Engmann, Lawrence


    To compare live birth rates after dual trigger of oocyte maturation with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders with peak E(2) triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation. GnRHa alone versus dual trigger. Live birth, implantation, and clinical pregnancy rates and OHSS. The dual-trigger group had a significantly higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%), and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger group. One case of mild OHSS occurred in the dual-trigger group, and there were no cases of OHSS in the GnRHa trigger group. Dual trigger of oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2) birth without increasing the risk of significant OHSS. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy

    De Gier, J.; Buijtels, J.J.C.W.M.; Albers-Wolthers, C.H.J.; Oei, C.H.Y.; Kooistra, H.S.; Okkens, A.C.


    GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma lute

  18. A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle.

    Koo, Hwa Seon; Cha, Sun Hwa; Kim, Hye Ok; Song, In Ok; Min, Eung Gi; Yang, Kwang Moon; Park, Chan Woo


    The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3±7.2 vs. 11.0±7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.

  19. Ovarian characteristics and timed artificial insemination pregnancy risk after presynchronization with gonadotropin-releasing hormone 7 days before PGF2α in dairy cows.

    Stevenson, J S


    The objective was to determine the benefit of including GnRH and PGF2α (PG) as a part of a presynchronization option before enrolling cows in a timed artificial insemination (AI) program. Holstein cows in one herd were assigned weekly at calving from January 2012 to August 2014 to a completely randomized design consisting of two presynchronization treatments. Cows in the Presynch-11 (n = 290) control were administered two PGF2α injections (Presynch PG-1 and Presynch PG-2) 14 days apart starting at 39 ± 4 days postpartum (study Days 0 and 14). Cows receiving the experimental presynchronization treatment (Gsynch-11, n = 287) were treated with GnRH (pre-GnRH) on study Day 7 and PG (pre-PG) on study Day 14. On study Day 25, all cows were enrolled in the Ovsynch-56 timed AI program: GnRH-1 on study Day 25, PG on study Day 32, GnRH-2 on study Day 34, 56 hours after PG, and timed AI on study Day 35, 16 hours after GnRH-2. In a subsample of 255 cows, ovarian structures were monitored for size and ovulation, and blood samples were collected on study Days 7, 14, 25, 32, 34, and 41 to measure progesterone. Concentrations of progesterone were greater (P 96%), ovulation to GnRH-2 (>90%), and synchronization risk (>88%) did not differ between treatments, but incidence of multiple ovulation after GnRH-2 was larger (P = 0.036) in Presynch-11 than Gsynch-11 cows (28.4% vs. 15.9%), respectively. Pregnancy per AI at 32 days (36.4% vs. 35.1%) and 60 days (30.0% vs. 29.0%) after AI did not differ between Gsynch-11 and Presynch-11 cows, respectively, but was suppressed during summer months in both treatments to less than 70% of the pregnancy per AI of nonsummer months. Because more than 90% of the cows were ovular as treatments were applied, the GnRH treatment of Gsynch-11 could not be assessed for its benefit in anovular cows. The Gsynch-11 presynchronization treatment performed comparably with the standard Presynch-11 program and provides a viable presynchronization option for use before first AI in dairy herds.

  20. Evaluation of gonadotropin-releasing hormone hydrogen chloride at 3 doses with prostaglandin F2α for fixed-time artificial insemination in dairy cows.

    Chenault, J R; Meeuwse, D M; LaGrow, C; Tena, J-K S; Wood-Follis, S L; Hallberg, J W


    The objectives of the current study were to evaluate the efficacy and field safety of GnRH HCl administered at 3 doses in fixed-time artificial insemination (FTAI) programs (Ovsynch) in dairy cows. A common protocol was conducted at 6 commercial dairies. Between 188 and 195 cows were enrolled at each site (total enrolled = 1,142). Cows had body condition scores ≥ 2 and ≤ 4, were between 32 to 140 d in milk, and were clinically healthy. Within pen and enrollment day (enrollment cohort), cows were assigned randomly in blocks of 4 to each of 4 treatments: (1) 25mg of PGF2α on d 7 with FTAI 72 ± 2 h later (control); (2) 100 μg of GnRH on d 0, d 7 a dose of 25mg of PGF2α, and the second administration of 100 μg of GnRH (T100) administered either at 48 ± 2 h (d 9) after PGF2α with FTAI 24 ± 2 h later or 56 ± 2 h (d 9) after PGF2α and FTAI 17 ± 2 h later; (3) same as T100 with both injections of 150 μg of GnRH (T150); and (4) same as T100 with both injections of 200 μg of GnRH (T200). Three sites selected the first option and 3 sites selected the second option for the timing of the second injection of all doses of GnRH. Cows were observed daily for signs of estrus and adverse clinical signs. Cows not returning to estrus had pregnancy diagnosis between 42 and 65 d following FTAI. Pregnancies per FTAI (P/FTAI) were analyzed as a binary variable (1 = pregnant, 0 = not pregnant) using a generalized linear mixed model with a binomial error distribution and a logit link function. The statistical model included fixed effects for treatment, random effects of site, site by treatment, enrollment cohort within site, and residual. Parity (first vs. second or greater) was included as a covariate. For demonstration of effectiveness, α=0.05 and a 2-tailed test were used. Fifty-two cows were removed from the study because of either deviation from the protocol, injury, illness, culling, or death. Among the remaining 1,090 cows, 33.9% were primiparous and 66.1% were multiparous. Back-transformed least squares means for P/FTAI were 17.1, 27.3, 29.1, and 32.2% for control, T100, T150 and T200, respectively. The P/FTAI for each GnRH dose differed from that of the control. No differences were detected in P/FTAI between GnRH doses. No treatment-related adverse events were observed. Mastitis was the most frequently observed adverse clinical sign, followed by lameness and pneumonia. This study documents the efficacy and safety of doses of 100 to 200 μg of GnRH as the HCl salt when used in Ovsynch programs.

  1. Increasing estradiol benzoate, pretreatment with gonadotropin-releasing hormone, and impediments for successful estradiol-based fixed-time artificial insemination protocols in dairy cattle.

    Monteiro, P L J; Borsato, M; Silva, F L M; Prata, A B; Wiltbank, M C; Sartori, R


    With the objective to optimize fixed-time artificial insemination (FTAI) protocols based on estradiol benzoate (EB) and progesterone (P4), we performed 2 experiments (Exp.) in dairy cows. In Exp. 1 (n=44), we hypothesized that increased EB (EB3=3 mg vs. EB2=2 mg) on d 0 would improve synchronization of ovarian follicle wave emergence. Likewise, in Exp. 2 (n=82), we hypothesized that a GnRH treatment on d -3 (early in a follicular wave on d 0) versus d -7 (presence of a dominant follicle on d 0) would better synchronize wave emergence. Moreover, results from both experiments were combined to identify reasons for the lack of synchronization. All cows were treated with EB at the time of introduction of a P4 implant (d 0). On d 7, cows were given 25 mg of prostaglandin F2α; on d 8, the implant was removed and cows were given 1mg of estradiol cypionate. All cows received FTAI on d 10. In both experiments, daily ultrasound evaluations were performed and, in Exp. 2, circulating P4 was evaluated during the protocol. Pregnancy per artificial insemination (P/AI) was determined on d 31 and 59 after FTAI. In Exp. 1, EB dose did not change time to wave emergence, but EB3 compared with EB2 decreased the percentage of cows with a corpus luteum on d 7 (19.8 vs. 55.3%) and time to ovulation (10.4 vs. 10.9 d). In Exp. 2, although we detected a tendency for delayed follicle wave emergence after the start of the FTAI protocol in cows ovulating to GnRH given on d -7, there was no difference in percentage of cows with a synchronized wave emergence (~80%). Regardless of treatment, more cows with P4<0.1 ng/mL, compared with P4≥0.1 and <0.22 ng/mL at the time of AI, ovulated to the protocol (81.2 vs. 58.0%) and had increased P/AI (47.4 vs. 21.4%). An analysis of data from both experiments showed that only 73.8% (93/126) of cows had synchronized wave emergence, and only 77.8% (98/126) of cows ovulated at the end of the protocol. Fertility was much greater in cows that had emergence of a new wave synchronized and ovulated to end of the protocol [P/AI 61.3% (46/75)] compared with cows that failed to present one or both of the outcomes above [15.7% (8/51)]. Thus, although current FTAI protocols using EB and P4 produce P/AI between 30 and 40% for lactating dairy cows, there remains room for improvement because less than 60% (75/126) of the cows were correctly synchronized. Starting the FTAI protocol without the dominant follicle or increasing the dose of EB to 3mg was not effective in increasing synchronization rate.

  2. Immunofluorescence studies on gonadotropin releasing hormone (GRH) in the fore-brain and the neurohypophysis of the green frog, Rana esculenta L.

    Goos, H J; Ligtenberg, P J; van Oordt, P G


    Using antibodies against mammalian LH-RH, the double antibody-immunofluorecence technique has been applied to serial cross sections of the brains of adult Rana esculenta. Immunoreactive material was found in perikarya of an unpaired nucleus in front of the preoptic recess. The axons of these perikarya also contain fluorescing material. They form a single bundle which passes under the preoptic recess, than splits into two tracts, one on either side of the optic chiasm. The two tracts reunite just before entering the median eminence. The axons end near the capillaries in the outer zone of the median eminence. The possibility of two separate centres for the stimulation of gonadotropic activity in the brains of anurans is discussed.

  3. Origins of gonadotropin-releasing hormone (GnRH) in vertebrates: identification of a novel GnRH in a basal vertebrate, the sea lamprey.

    Kavanaugh, Scott I; Nozaki, Masumi; Sower, Stacia A


    We cloned a cDNA encoding a novel (GnRH), named lamprey GnRH-II, from the sea lamprey, a basal vertebrate. The deduced amino acid sequence of the newly identified lamprey GnRH-II is QHWSHGWFPG. The architecture of the precursor is similar to that reported for other GnRH precursors consisting of a signal peptide, decapeptide, a downstream processing site, and a GnRH-associated peptide; however, the gene for lamprey GnRH-II does not have introns in comparison with the gene organization for all other vertebrate GnRHs. Lamprey GnRH-II precursor transcript was widely expressed in a variety of tissues. In situ hybridization of the brain showed expression and localization of the transcript in the hypothalamus, medulla, and olfactory regions, whereas immunohistochemistry using a specific antiserum showed only GnRH-II cell bodies and processes in the preoptic nucleus/hypothalamus areas. Lamprey GnRH-II was shown to stimulate the hypothalamic-pituitary axis using in vivo and in vitro studies. Lamprey GnRH-II was also shown to activate the inositol phosphate signaling system in COS-7 cells transiently transfected with the lamprey GnRH receptor. These studies provide evidence for a novel lamprey GnRH that has a role as a third hypothalamic GnRH. In summary, the newly discovered lamprey GnRH-II offers a new paradigm of the origin of the vertebrate GnRH family. We hypothesize that due to a genome/gene duplication event, an ancestral gene gave rise to two lineages of GnRHs: the gnathostome GnRH and lamprey GnRH-II.

  4. Microarray studies in high and low RFI cattle reveal a potential role for gonadotropin releasing hormone (GnRH) in regulating feed efficiency

    Residual feed intake (RFI) is a heritable feed efficiency measure. Mechanisms underlying variation in feed efficiency are currently poorly understood. To address this issue, two divergent cohorts consisting of High (H) and Low (L) RFI individuals were created by assessing RFI in forty-eight Angus-si...

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

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


    pituitary gland from which a nearly pure population of PRL cells can be isolated, we examined whether GnRH might stimulate PRL release through an increase in phospholipase C (PLC), inositol triphosphate (IP3), and intracellular calcium (Ca(i)2+) signaling. Using Ca(i)2+ imaging and the calcium-sensitive dye...... fura-2, we found that chicken GnRH-II (cGnRH-II) induced a rapid dose-dependent increase in Ca(i)2+ in dispersed tilapia lactotrophs. The Ca(i)2+ signal was abolished by U-73122, an inhibitor of PLC-dependent phosphoinositide hydrolysis. Correspondingly, cGnRH-II-induced tPRL188 secretion was inhibited...... by U-73122, suggesting that activation of PLC mediates cGnRH-II's stimulatory effect on PRL secretion. Pretreatment with 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of Ca2+ release from intracellular stores, impeded the effect of cGnRH-II on Ca(i)2...

  6. Stimulation of gastric bicarbonate secretion by an analog of thyrotropin-releasing hormone, YM-14673, in the rat.

    Takeuchi, K; Ueshima, K; Okabe, S


    The effects of YM-14673, a thyrotropin-releasing hormone analog, on gastric alkaline secretion were investigated in the anesthetized rat pretreated with omeprazole (60 mg/kg, intraperitoneally) by measuring the luminal pH, transmucosal PD and HCO3- output. The whole stomach was perfused at a flow rate of 0.7 ml/min with saline (pH 4.5) in the absence of acid secretion, the pH of the perfusate and PD were continuously monitored and the HCO3- output was measured as acid-neutralizing capacity by back-titration of the perfusate to pH 4.5. YM-14673, given intravenously at the doses (0.1-1 mg/kg) that stimulated acid secretion, increased the pH and HCO3- output in a dose-dependent fashion, but did not significantly affect the PD. Prostaglandin E2 (1 mg/kg) elevated the pH and HCO3- output with concomitant decrease in the PD, whereas carbachol (4 micrograms/kg), similar to YM-14673, produced an increase of the pH and HCO3- output with no change in the PD. The net HCO3- output (4.3 +/- 0.3 muEq) induced by 0.3 mg/kg of YM-14673 was about 60 and 150% of that induced by prostaglandin E2 and carbachol, respectively. The increased pH and HCO3- responses caused by YM-14673 were almost completely abolished by vagotomy, significantly inhibited by atropine (0.3 mg/kg, intravenously) and indomethacin (5 mg/kg, subcutaneously) but not affected by pirenzepine (1 mg/kg, intravenously). These results suggest that YM-14673, a thyrotropin-releasing hormone analog, produced vagally mediated HCO3- secretion in the rat stomach, and the mechanism may involve the cholinergic system, which is mediated with muscarinic M2 receptors and interacts with endogenous prostaglandins.

  7. Larval Exposure to the Juvenile Hormone Analog Pyriproxyfen Disrupts Acceptance of and Social Behavior Performance in Adult Honeybees.

    Julie Fourrier

    Full Text Available Juvenile hormone (JH plays an important role in honeybee development and the regulation of age-related division of labor. However, honeybees can be exposed to insect growth regulators (IGRs, such as JH analogs developed for insect pest and vector control. Although their side effects as endocrine disruptors on honeybee larval or adult stages have been studied, little is known about the subsequent effects on adults of a sublethal larval exposure. We therefore studied the impact of the JH analog pyriproxyfen on larvae and resulting adults within a colony under semi-field conditions by combining recent laboratory larval tests with chemical analysis and behavioral observations. Oral and chronic larval exposure at cumulative doses of 23 or 57 ng per larva were tested.Pyriproxyfen-treated bees emerged earlier than control bees and the highest dose led to a significant rate of malformed adults (atrophied wings. Young pyriproxyfen-treated bees were more frequently rejected by nestmates from the colony, inducing a shorter life span. This could be linked to differences in cuticular hydrocarbon (CHC profiles between control and pyriproxyfen-treated bees. Finally, pyriproxyfen-treated bees exhibited fewer social behaviors (ventilation, brood care, contacts with nestmates or food stocks than control bees.Larval exposure to sublethal doses of pyriproxyfen affected several life history traits of the honeybees. Our results especially showed changes in social integration (acceptance by nestmates and social behaviors performance that could potentially affect population growth and balance of the colony.

  8. Improving the outcome of established therapies for osteoporosis by adding the active D-hormone analog alfacalcidol.

    Ringe, J D; Schacht, E


    While in other chronic diseases combined treatment regimens are the rule there is a lack of reported experience or study data on combining different specific drugs to treat osteoporosis. Significant differences in the mode of action (MOA) of the substances to be combined may be important for achieving optimal therapeutic results. Recognising that today bisphosphonates are the leading therapy for osteoporosis we suggest that the active D-hormone analog alfacalcidol with its completely different mechanisms of action could be an interesting combination to improve the therapeutic outcome of the pure antiresoptive action of bisphosphonates. Alfacalcidol is activated by the enzyme 25-hydroxylase in the liver for systemic and in osteoblasts for local D-hormone actions. It possesses a unique pattern of pleiotropic effects on, e.g. gut, bone, pararthyroids, muscle and brain. Alfacalcidol is superior to plain vitamin D (cholecalciferol) because the final kidney activation of the latter is regulated by a negative feedback mechanism. In vitamin D replete patients or patients with impaired kidney function no increased D-hormone action at the target tissues can be achieved. Animal studies and several trials in humans with alendronate plus calcitriol or alfacalcidol proved that the combination induced significantly higher increases of bone mineral density (BMD) than the respective mono-therapies. The results of the 2-year AAC-trial from our group indicate that the combination alendronate and alfacalcidol is also superior in terms of falls, fractures and back pain. From the review of the literature and the own new results we conclude that this combined therapeutic regimen is a very promising option for treating established osteoporosis and propose a differentiated use of alfacalcidol alone or the combination with alendronate in different stages and clinical situations of osteoporosis.

  9. Backbone metal cyclization: Novel {sup 99m}Tc labeled GnRH analog as potential SPECT molecular imaging agent in cancer

    Barda, Yaniv; Cohen, Nasi; Lev, Vered; Ben-Aroya, Nurit; Koch, Yitzhak; Mishani, Eyal; Fridkin, Mati; Gilon, Chaim E-mail:


    Gonadotropin-releasing hormone (GnRH) is a decapeptide secreted to the pituitary where it binds to specific receptors on the gonadotropes to regulate gonadotropic hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) synthesis and secretion. Specific GnRH receptors are overexpressed in breast, prostatic, ovarian, and other tumors. The aim of this study was to synthesize a cyclic GnRH analog with high affinity to GnRH receptors that can be radiolabeled with {sup 99m}Tc. A precyclic GnRH analog, [Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (Gn-2), containing two hemi-chelator groups was synthesized. It was cyclized applying the recently reported backbone metal cyclization (BMC) approach, to obtain cyclo(Re(O)1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (cyclo[Re(O)-Gn-2]). For comparative evaluations, Gn-2 was oxidized on-resin to yield cyclo(S-S,1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH, (cyclo[S-S-Gn-2]). The binding affinity of cyclo[Re(O)-Gn-2] to rat pituitary membranes showed IC{sub 50} of 50nM, compared to IC{sub 50} = 10 nM in the native GnRH. Cyclo({sup 99m}Tc(O)1-10)[Cys-Gly]{sup 1}[D-Ala]{sup 6}[N{sup {alpha}}({eta}-Cys-amino hexyl)]{sup 10}GnRH (cyclo[{sup 99m}Tc(O)-Gn-2]) was synthesized from Gn-2 and showed similar chromatographic behavior to its rhenium surrogate.

  10. Enhancing male sexual success in a lekking fly (Ananstrepha suspensa (Diptera: Tephritidae) through a juvenile hormone analog has no effect on adult mortality

    While defending lek-territories, male Anastrepha suspensa (Loew) produce chemical, acoustic and visual courtship signals. In the laboratory and under semi-natural conditions, topical application of the juvenile hormone analog methoprene doubles pheromone production and subsequently doubles sexual su...

  11. Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors

    L.J. Hofland (Leo); W.W. de Herder (Wouter); H.A. Visser-Wisselaar (Heleen); C. van Uffelen; M. Waaijers (Marlijn); J. Zuyderwijk; P. Uitterlinden (Piet); P.M. van Koetsveld (Peter); S.W.J. Lamberts (Steven); J.M. Kros (Johan)


    textabstractThe effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7

  12. Hormones

    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, ...

  13. Effects of follicle-stimulating hormone with and without luteinizing hormone on serum hormone concentrations, follicle growth, and intrafollicular estradiol and aromatase activity in gonadotropin-releasing hormone-immunized heifers.

    Crowe, M A; Kelly, P; Driancourt, M A; Boland, M P; Roche, J F


    To evaluate the roles of FSH and LH in follicular growth, GnRH-immunized anestrous heifers (n = 17) were randomly assigned (Day 0) to one of three groups (n = 5 or 6). Group 1 received i.m. injections of 1.5 mg porcine FSH (pFSH) 4 times/day for 2 days; group 2 received i.v. injections of 150 microg pLH 6 times/day for 6 days; group 3 received both pFSH and pLH as described for groups 1 and 2. After slaughter on Day 6, measurements were made of follicle number and size, and follicular fluid concentrations of progesterone (P(4)), estradiol (E(2)), and aromatase activity. Injection of pFSH increased (P: pLH increased (P: pLH than those given either pFSH or pLH alone. There was no difference (P: > or = 0.24) between treatments in the number of small follicles (pLH had more (P: pLH alone (none present). Heifers given pFSH + pLH had more (P: = 0.04) large follicles (> or =10 mm) than those given either pLH or pFSH alone (none present). Overall, only 1 of 35 small follicles and 2 of 96 medium follicles were E(2)-active (i.e., E(2):P(4) >1.0), whereas 18 of 21 large follicles (all in the pFSH + pLH treatment) were E(2)-active; of these, 8 of 18 had aromatase activity. Concentrations of E(2) and E(2) activity in follicular fluid were correlated (r > or = 0.57; P: pLH + pFSH. In conclusion, pLH failed to stimulate follicle growth greater than 5 mm; pFSH stimulated growth of medium follicles that were E(2)-inactive at slaughter and failed to increase serum E(2) concentrations; whereas pFSH + pLH stimulated growth of medium follicles and E(2)-active large follicles, and a 10- to 14-fold increase in serum E(2) concentrations.

  14. Hormonal contraception for human males: prospects



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

  15. Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice.

    Trousdale, Rhonda K; Yu, Bo; Pollak, Susan V; Husami, Nabil; Vidali, Andrea; Lustbader, Joyce W


    To compare the efficacy of recombinant human FSH (rhFSH) with rhFSH with four additional O-linked carbohydrates (rhFSH-CTP), rhFSH with four additional N-linked carbohydrates (rhFSH-N4), and the current gold standard for rodent ovarian stimulation, pregnant mare serum gonadotropin (PMSG), on fertility parameters in mice. Animal study. Academic research center. Adult C57Bl/6J female mice. Ovarian stimulation with 5 IU of rhFSH, rhFSH-CTP, rhFSH-N4, or PMSG. Forty-six hours later, 5 IU of hCG was injected to promote ovulation and females were mated overnight. Eggs retrieved after ovulation, in vitro embryo development, delivery rate, and litter size. The hyperglycosylated FSH analogs, rhFSH-CTP and rhFSH-N4, enhanced ovulation and embryo maturation significantly better than rhFSH. RhFSH-N4 produced more eggs (28.5 +/- 1.9 per mouse) and embryos (17.8 +/- 1.6) compared with rhFSH-CTP (18.3 +/- 1.2 and 9.0 +/- 1.0, respectively). Treatment with rhFSH, rhFSH-N4, and PMSG produced statistically equivalent delivery rates and litter sizes. The delivery rate was surprisingly lower with rhFSH-CTP (14%) compared with PMSG (33%). Compared with rhFSH, treatment with hyperglycosylated rhFSH-CTP and rhFSH-N4 led to superior rates of ovulated eggs and subsequent in vitro embryo development. RhFSH-N4 was equivalent to PMSG, while all of the fertility parameters studied were lower with rhFSH-CTP than with PMSG therapy.

  16. Design and characterization of a fluorescent ghrelin analog for imaging the growth hormone secretagogue receptor 1a.

    McGirr, Rebecca; McFarland, Mark S; McTavish, Jillian; Luyt, Leonard G; Dhanvantari, Savita


    Ghrelin is a 28-amino acid peptide hormone produced in the stomach. It binds to the growth hormone secretagogue receptor 1a (GHS-R1a), a class A G-protein-coupled receptor. In the present study, we describe the design, synthesis and characterization of a truncated, 18-amino acid analog of ghrelin conjugated to a fluorescent molecule, fluorocein isothiocyanate (FITC), through the addition of a lysine at its C terminus ([Dpr(octanoyl)(3), Lys(fluorescein)(19)]ghrelin(1-19)). Receptor binding affinity of this novel fluorescein-ghrelin(1-18) was similar to that of wild-type ghrelin and a synthetic GHS-R1a ligand, hexarelin. Live cell imaging in CHO/GHS-R1a cells demonstrated cell surface receptor labeling and internalization, and agonist activity of fluorescein-ghrelin(1-18) was confirmed by increased phosphorylation of ERK1/2. We also show that GHS-R1a protein is expressed primarily in the heart when compared to all other organs, suggesting high receptor density in the left ventricle. Finally, we demonstrate that fluorescein-ghrelin(1-18) binds specifically to heart tissue in situ, and its binding is displaced by both wt ghrelin and hexarelin. We have therefore developed a novel imaging probe, fluorescein-ghrelin(1-18), that can be used to image GHS-R1a in situ, for the purposes of investigating mechanisms of receptor trafficking or pharmacological agents that target GHS-R1a.

  17. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Thomas P Quinn


    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  18. A novel, mild, specific and indirect maleimido-based radioiodolabeling method; Radiolabeling of analogs derived from parathyroid hormone (PTH) and PTH-related protein (PTHrP)

    Chorev, M.; Caulfield, M.P.; Roubini, E.; McKee, R.L.; Gibbons, S.W.; Chih-Tai Leu; Levy, J.J.; Rosenblatt, M.


    In an effort to design a mild, non-oxidative and site-specific means of radiolabeling bioactive molecules we have employed maleimido-sulfhydryl chemistry to produce bioactive hormone radioligands. We have prepared two novel radioiodolabeled reagents, 3'-maleimidopropanoyl-3-[sup 125]I-tyramide and its retro analog, N-maleoyl-N'-3-(4-hydroxy-3-[sup 125]I-phenyl)propanoyl ethylenediamide, by either oxidative radioiodination of the precursors or radiolabeling of the phenolic component prior to its incorporation into the radiolabeling reagents. These reagents were then used to radiolabel analogs of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) in an efficient way, yielding reaction mixtures which were easily purified. The radioligands obtained are stable upon storage and bind in an reversible manner to a single population of binding sites displaying affinity in the low nanomolar range. The potencies of these analogs are comparable to the non-modified PTH and PTH rP analogs. This study demonstrates the utility of the novel maleimido-based indirect radioiodination approach and highlights some of its advantages over either direct oxidative procedures or acylation using the Bolton-Hunter reagent. (au).

  19. Juvenile hormone analog technology: effects on larval cannibalism and the production of Spodoptera exigua (Lepidoptera: Noctuidae) nucleopolyhedrovirus.

    Elvira, Sonia; Williams, Trevor; Caballero, Primitivo


    The production of a multiple nucleopolyhedrovirus (SeMNPV) of the beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), has been markedly increased by using juvenile hormone analog (JHA) technology to generate a supernumerary sixth instar in the species. In the current study we compared the incidence of cannibalism in S. exigua fifth and sixth instars reared at low (two larvae per dish) and a high density (10 larvae per dish). The incidence of cannibalism was significantly higher in fifth instars compared with sixth instars and increased with rearing density on both instars. Infected larvae were more prone to become victims of cannibalism than healthy individuals in mixed groups comprising 50% healthy + 50% infected larvae in both instars reared at high density. Instar had a marked effect on occlusion body (OB) production because JHA-treated insects produced between 4.8- and 5.6-fold increase in OB production per dish compared with fifth instars at high and low densities, respectively. The insecticidal characteristics of OBs produced in JHA-treated insects, as indicated by LD50 values, were similar to those produced in untreated fourth or fifth instars. Because JHA technology did not increase the prevalence of cannibalism and had no adverse effect on the insecticidal properties of SeMNPV OBs, we conclude that the use of JHAs to generate a supernumerary instar is likely to be compatible with mass production systems that involve gregarious rearing of infected insects.

  20. Juvenile hormone analog enhances calling behavior, mating success, and quantity of volatiles released by Anastrepha obliqua (Diptera: Tephritidae).

    Chacón-Benavente, Roxana; López-Guillen, Guillermo; Hernández, Emilio; Rojas, Julio C; Malo, Edi A


    The application of a juvenile hormone analog, methoprene, to newly emerged adult males reduced the time required for sexual maturation and enhanced mating success in several species of tephritid fruit flies. In this work, we investigated the effect of topical methoprene application on West Indian fruit fly, Anastrepha obliqua (Macquart), male calling, mating, and volatile release. Males treated with topical methoprene exhibited sexual maturation and reproductive behavior 2 d earlier when compared with control males treated with acetone. Methoprene-treated males began calling and mating at 4 d old, whereas control males did not call and mate until 6 d old. The gas chromotography-mass spectrometry analysis of volatiles showed that during calling A. obliqua males consistently released four compounds; three of them were identified as (Z)-3-nonenol, (Z,E)-α-farnesene, (E,E)-α-farnesene, and a fourth compound with the appearance of a farnesene isomer. Both treated and control males released the same compounds, although treated males started to release volatiles before that control males. The results are discussed in view of possible methoprene application with the aim of reducing costs in fly emergence and release facilities before eventual release of A. obliqua in the field, thus improving the sterile insect technique.

  1. Juvenile hormone (JH esterase of the mosquito Culex quinquefasciatus is not a target of the JH analog insecticide methoprene.

    Shizuo G Kamita

    Full Text Available Juvenile hormones (JHs are essential sesquiterpenes that control insect development and reproduction. JH analog (JHA insecticides such as methoprene are compounds that mimic the structure and/or biological activity of JH. In this study we obtained a full-length cDNA, cqjhe, from the southern house mosquito Culex quinquefasciatus that encodes CqJHE, an esterase that selectively metabolizes JH. Unlike other recombinant esterases that have been identified from dipteran insects, CqJHE hydrolyzed JH with specificity constant (k(cat/K(M ratio and V(max values that are common among JH esterases (JHEs. CqJHE showed picomolar sensitivity to OTFP, a JHE-selective inhibitor, but more than 1000-fold lower sensitivity to DFP, a general esterase inhibitor. To our surprise, CqJHE did not metabolize the isopropyl ester of methoprene even when 25 pmol of methoprene was incubated with an amount of CqJHE that was sufficient to hydrolyze 7,200 pmol of JH to JH acid under the same assay conditions. In competition assays in which both JH and methoprene were available to CqJHE, methoprene did not show any inhibitory effects on the JH hydrolysis rate even when methoprene was present in the assay at a 10-fold higher concentration relative to JH. Our findings indicated that JHE is not a molecular target of methoprene. Our findings also do not support the hypothesis that methoprene functions in part by inhibiting the action of JHE.


    Watson, Sara E.; Greene, Ariana; Lewis, Katherine; Eugster, Erica A.


    Objective Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. Methods We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. Results A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). Conclusion Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP. PMID:25667370

  3. [Hormonal stimulation of reproductive function in swine].

    Hladkova, A I


    Industrial conditions, gynaecological disorders, ovarian deficiency being unfavourable factors for pigs reproduction, as well as the necessity in rapid sex maturation require thorough knowledge on physiology of reproduction processes. The importance belongs to the hormonal treatment in development of special biotechnological methods. Efficiency of the latter is determined by the kind of hormone used, its dose, injection time in sex cycle and the knowledge of species specificity of physiological regulation of reproductive processes in pigs of great value. The achievements in this country and abroad, devoted to the technology of oestrogens, gestagens, androgens and their combinations as well as gonadotropins (PMS, CG), gonadotropin-releasing hormone applications have been reviewed. The most often used schemes of hormonal treatment and drugs, as well as the results obtained have been described. The data presented can be used for needs of practical cattle-breeding.

  4. Reversal of hemorrhagic shock in rats using the metabolically stable thyrotropin-releasing hormone analog taltirelin hydrate.

    Asai, Hidetoshi; Watanabe, Yumi; Yamauchi-Kohno, Rikako; Doi, Osamu


    We investigated the effect of taltirelin hydrate ((−)-N-[(S)-hexahydro-1-methyl- 2,6-dioxo-4-pyrimidinyl-carbonyl]-L-histidyl-L-prolinamide tetrahydrate; taltirelin), a metabolically stable thyrotropin-releasing hormone (TRH) analog, on circulatory function, respiratory function, and viable time after bleeding in urethane-anesthetized rats. Massive volume-controlled bleeding caused marked reductions in mean arterial pressure (MAP) and respiratory rate (RR). The vital signs of control rats were lost within an average of 23 min after bleeding. Intravenous administration of taltirelin (0.03−0.3 mg/kg) and TRH (1 and 3 mg/kg) immediately after bleeding accelerated recovery of MAP and RR, and prolonged viable time in a dose-dependent manner. The potency of taltirelin in accelerating MAP and RR recovery and prolonging viable time was higher when compared with that of TRH. In addition, recovery of MAP and RR and the extension of viable time by taltirelin were inhibited by preintraperitoneal administration of atropine sulfate, which is a centrally acting muscarinic antagonist, but not by that of atropine methylbromide, which is a peripherally acting muscarinic antagonist. Taltirelin also recovered decreased arterial pH, bicarbonate ions, and base excess, and prevented a decrease in arterial oxygen saturation. In conclusion, the anti-shock effect of taltirelin was more potent than that of TRH. Taltirelin activity was mediated by the central muscarinic cholinergic system. In addition, taltirelin also corrected metabolic acidosis. These results suggest that taltirelin could be useful in the treatment of hypovolemic shock.

  5. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta


    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  6. Gonadothropin-releasing hormone agonist as a treatment of choice for central precocious puberty

    Jose R.L. Batubara


    Full Text Available Precocious puberty is defi ned as pubertal development which occurs too early. The age limit in this term is based on the onset of puberty in normal population. Some points have to be taken into account, such as ethnicity, gender, nutritional conditions, and secular trends. In girls, precocious puberty is defi ned by breast development occured before 8 years old. In boys, precocious puberty is defi ned as gonadarche or pubarche before 9 years of age. The clinical course of precocious puberty varies widely, ranging from alternating, slowly progressive, and rapidly progressive    form. The rapidly progressive forms of idiopathic central precocious puberty need to be treated because it may result in early epiphyseal closure and short fi nal height, and also pyschosocial problems in the affected children and the family. The aims of treatment are to arrest physical maturation, prevent early menarche, and also improve adult height combined with normal body proportions. Gonadotropin releasing hormone analogue is the treatment of choice for central precocious puberty. Gonadotropin releasing horomone analogue has suppressive effect on the pituitarygonadal axis, therefore it suppresses LH secretion. This leads to the return of estradiol and testosterone to prepubertal levels. Treatment using gonadotropin releasing horomone analogue is shown to reduce breast size, pubic hair, ovarian and uterine size in girls, and decrease testicular size in boys. Gonadotropin releasing hormone analogue is effective in halting progression of secondary sexual characteristics development, presenting menstrual cycle, slowing bone-age advancement, and also improving fi nal height. (Med J Indones 2010; 19:287-92Keywords: gonadache, GRH analogue, pubarche , precocious puberty

  7. Synthesis of analogs of juvenile hormone on the basis of the telomerization reaction of piperylene with sulfones

    Tolstikov, G.A.; Rozentsvet, O.A.; Pantukh, B.I.; Khalilov, L.M.


    In continuing the work on the study of the telomerization of 1,3-dienes with sulfones containing an active H atom, and also with the aim of synthesizing analogs of juvenile hormone (JH) based on the telomers obtained, they studied the catalytic telomerization of 1,3-pentadiene (piperylene) with ..beta..-substituted sulfonates. It was established that trans-piperlyene participates in the telomerization reaction with sulfones in the presence of the catalytic system PdCl/sub 2/(Ph/sub 3/P)/sub 2/-PhONa. Methyl 2-phenylsulfonyl-3,7-dimethyl-4(E), 9-decadienecarboxylate (II) is formed in a yield of 65% by the reaction of methyl phenylsulfonylacetate (I) with piperylene in the course of 20 h at 85/sup 0/C. The presence of absorption bands at 920 (CH/sub 2/=C) and 980 cm/sup -1/ (E-CH=CH) in the IR spectrum of compound (II) and the presence of a group of multiplet signals at delta 4.8-5.3 ppm in the PMR spectrum, corresponding to five protons of double bonds, indicate the addition of two molecules of piperylene to the molecule of the sulfone (I). The oxidation with oxygen on a Pd/Cu-catalyst proceeds smoothly to the methyl ketone (III); this clearly confirms the presence of the terminal C=C bond in the telomer (II). In the PMR spectrum of (II), notice is taken of the group of signals in the region of 3.30-3.53 ppm corresponding to three methoxy protons. There are three pairs of doublets (J = 7 Hz) in the region of 0.1-1.3 ppm which correspond to the methyl group. The complexity of the PMR spectrum is probably explained by the fact that the reaction leads to the formation of a complex mixture of diastereoisomers. As was to be expected, methyl 3,7-dimethyl-4,9-decadienoate (IV) is formed as the sole product with a yield of 70% in the desulfonation of the telomer (II) using Na/Hg in methanol according to the method of (5); the structure of (IV) was established with the aid of /sup 13/C NMR spectroscopy.

  8. Structural and Functional Divergence of Gonadotropin-Inhibitory Hormone (GnIH from Jawless Fish to Mammals

    Satoshi eOgawa


    Full Text Available Gonadotropin-inhibitory hormone (GnIH was discovered as a novel hypothalamic peptide that inhibits gonadotropin release in the quail. The presence of GnIH-homologous peptides and its receptors (GnIHRs have been demonstrated in various vertebrate species including teleosts, suggesting that the GnIH-GnIHR family is evolutionarily conserved. In avian and mammalian brain, GnIH neurons are localised in the hypothalamic nuclei and their neural projections are widely distributed. GnIH acts on the pituitary and gonadotropin-releasing hormone (GnRH neurons to inhibit reproductive functions by decreasing gonadotropin release and synthesis. In addition, GnIH-GnIHR signalling is regulated by various factors such as environmental cues and stress. However, the function of fish GnIH-orthologs remain inconclusive because the physiological properties of fish GnIH peptides are debatable. This review summarizes the current research progress in GnIH-GnIHR signalling and their physiological functions in vertebrates with special emphasis on non-mammalian vertebrate species.

  9. Synthetic peptide with inhibin-like activity preferentially inhibits follitropin secretion in comparison with lutropin-releasing hormone antagonists

    Sairam, M.R.; Ramasharma, K.; Li, C.H.


    Biological activity of a synthetic peptide with inhibin-like activity under in vitro and in vivo conditions was compared with three highly potent synthetic lutropin-releasing hormone antagonists. Unlike the synthetic lutropin-releasing hormone antagonists, which effectively inhibited both lutropin and follitropin secretion from the pituitary, the inhibin-like peptide showed a preferential effect by inhibiting follitropin release both in vitro and in vivo. Thus, small peptides such as inhibin-like peptide with a sequence unrelated to lutropin-releasing hormone may provide a basis for design of selective inhibitors of gonadotropin release. FSH and LH were measured by radioimmunoassay.

  10. Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

    Adoption of the hybrid catfish (channel catfish, Ictalruus punctatus, female x blue catfish, I. furcatus, male) is increasing in the catfish industry. The most effective way to produce fry is hormone induced spawning of females coupled with hand stripping and in vitro fertilization. The success of...

  11. Functional and neurophysiological evidence of the efficacy of trophic pharmacotherapy using an adrenocorticotrophic hormone4-9 analog in experimental allergic encephalomyelitis, an animal model of multiple sclerosis.

    Duckers, H J; van Dokkum, R P; Verhaagen, J; Lopes da Silva, F H; Gispen, W H


    Chronic experimental allergic encephalomyelitis (CEAE) is a well-established animal model for the human syndrome, multiple sclerosis. CEAE has striking histological, electrophysiological and clinical analogies with multiple sclerosis and is a valuable animal model for the preclinical pharmacotherapeutical development of new putative therapeutic agents. In this paper, we describe a neurotrophic repair approach in Lewis rats suffering from CEAE. The neurotrophic peptide used is a degradation resistant adrenocorticotrophic hormone4-9 analog. The development of CEAE was examined using a combination of clinical, functional and electrophysiological parameters including somatosensory and motor evoked potentials. The latencies and amplitudes of the various evoked potentials can provide quantitative, objective data regarding the involvement of different nerve tracts in CEAE and the effectiveness of the neurotrophic peptide. Repeated subcutaneous injections of the neurotrophic peptide suppressed the development of CEAE-related clinical symptoms, markedly improved motor performance and reduced the reaction time upon thermal stimulation as compared to saline-treated CEAE animals during a 17 week follow-up study. Prolonged onset latencies of corticomotor evoked potentials and peak latencies of somatosensory evoked potentials due to the demyelination were normalized upon peptide treatment. In addition, peptide treatment substantially prevented total blocking of the corticomotor pathway in CEAE-animals and reduced the attenuation of sensory evoked potentials-related peak amplitudes as compared to saline-treated animals. The functional and electrophysiological improvements observed in CEAE-animals treated with the adrenocorticotrophic hormone4-9 analog, suggest that a neurotrophic repair approach could be of great value to promote the restoration of function in a disabling demyelinating disorder.

  12. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.


    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  13. Early luteal phase endocrine profile is affected by the mode of triggering final oocyte maturation and the luteal phase support used in recombinant follicle-stimulating hormone-gonadotropin-releasing hormone antagonist in vitro fertilization cycles

    Fatemi, Human M; Polyzos, Nikolaos P; van Vaerenbergh, Inge


    To assess endocrine differences during early luteal phase according to mode of triggering final oocyte maturation with or without luteal phase support (LPS).......To assess endocrine differences during early luteal phase according to mode of triggering final oocyte maturation with or without luteal phase support (LPS)....

  14. Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 1. Discovery of gonadotropin-inhibitory hormone (GnIH) across vertebrates.

    Tsutsui, Kazuyoshi; Ubuka, Takayoshi


    Bargmann-Scharrer's discovery of "neurosecretion" in the first half of the 20th century has since matured into the scientific discipline of neuroendocrinology. Identification of novel neurohormones, such as neuropeptides and neurosteroids, is essential for the progress of neuroendocrinology. Our studies over the past two decades have significantly broadened the horizons of this field of research by identifying novel neuropeptides and neurosteroids in vertebrates that have opened new lines of scientific investigation in neuroendocrinology. Since the discovery of gonadotropin-releasing hormone (GnRH) in mammals at the beginning of 1970s, it was generally believed that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, we discovered a novel hypothalamic neuropeptide that actively inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). It now appears that GnIH is highly conserved across vertebrates, including humans, and serves a number of behavioral and physiological functions other than regulation of reproduction, providing enormous opportunity for investigators from a wide array of disciplines to study this neuropeptide. This review summarizes the discovery of GnIH and its contribution to the progress of neuroendocrinology.




    Full Text Available Pregnancy rate, estrous cycle lenght, serum progesterone and luteinizing hormone (LH concentrations were determined in gonadotropin releasing hormone (GnRH; 10.5 μg synthetic gonadotrophin releasing hormone agonist, receptal administered cows on day 12 post-mating (n=9 compared to control cows (n=8. Their oestrous cycles were synchronised by intramuscular administration of prostaglandin F2 alpha (its analog, cloprostenol twice at 11 days interval. Estrous exhibited cows were mated naturally. Blood samples were collected every two days from all animals. Serum progesterone and LH concentrations were measured by ELISA method. GnRH administration significantly increased serum LH concentration which reached peak levels 2-3 h after treatment. However, serum progesterone concentration was not affected. There were no differences in mean progesterone concentrations on days 12 to 24 post-mating between GnRH administrated and control pregnant cows. However, in non pregnant animals, progesterone concentrations on days 16 in the treated group were lower than control group (P<0.01. Pregnancy diagnosis in animals made by B-mode ultrasonography between the 30th and 35th day showed that 77.7% of treated cows were pregnant compared to 50% in control group. Duration of the estrous cycle in the non-pregnant animals was not affected by the treatment (control, 21.3 ± 0.8 days; treated, 22.5 ± 0.5 days. In conclusion, this study supports the use of GnRH on day 12 post-mating as a method for enhancing pregnancy rates in lactating dairy cattle.

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

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


    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...... the hypothalamopituitary-gonadal axis as well as on growth hormone (GH) secretion. Gonadal activity is increased in children with CPP; during GnRHa therapy secretion of gonadal hormones is suppressed as reflected by measurements of LH, FSH, and estradiol/testosterone. More recently, studies of levels of inhibin A and B...... as well as markers of androgen action such as SHBG and prostate specific antigen have demonstrated marked suppression of gonadal function possibly to infra-physiological levels. The possible long-term consequences of these observations have yet to be determined. Detailed analyses of the GH-IGF-I axis have...

  17. A PEGylated analog of the gut hormone oxyntomodulin with long-lasting antihyperglycemic, insulinotropic and anorexigenic activity.

    Bianchi, Elisabetta; Carrington, Paul E; Ingallinella, Paolo; Finotto, Marco; Santoprete, Alessia; Petrov, Aleksandr; Eiermann, George; Kosinski, Jennifer; Marsh, Donald J; Pocai, Alessandro; SinhaRoy, Ranabir; Pessi, Antonello


    Peptide agonists of the glucagon-like peptide 1 (GLP-1) receptor (GLP1R) are rapidly gaining favor as antidiabetic agents, since in addition to increasing glucose-dependent insulin secretion, they also cause weight loss. Oxyntomodulin (OXM), a natural peptide with sequence homology to both glucagon and GLP-1, has glucose-lowering activity in rodents and anorectic activity in rodents and humans, but its clinical utility is limited by a short circulatory half-life due to rapid renal clearance and degradation by dipeptidyl peptidase IV (DPP-IV). Here, we describe the development of a novel DPP-IV-resistant, long-acting GLP1R agonist, based on derivatization of a suitably chosen OXM analog with high molecular weight polyethylene glycol (PEG) ('PEGylation'). PEG-OXM exerts an anti-hyperglycemic effect in diet-induced obese (DIO) mice in a glucose-dependent manner, with a maximally efficacious dose of 0.1mg/kg, and reduces food intake and body weight with a minimally efficacious dose of 1mg/kg. If this pharmacology is recapitulated in patients with type 2 diabetes, these results indicate PEG-OXM as a potential novel once-weekly GLP-1 mimetic with both glucose-lowering activity and weight loss efficacy.

  18. Update on the male hormonal contraceptive agents.

    Walton, Melanie; Anderson, Richard A


    There remains a need for new acceptable and effective male contraceptives to increase the choice for couples throughout the world. There have been no recent advances in available male contraceptive methods although a number of promising approaches have been identified, of which the hormonal approach is currently undergoing clinical investigation. In recent years the pace of research in this area has quickened significantly with increasing interest and now investment by the pharmaceutical industry. This is vital if the work undertaken so far by the public sector is to be transformed into a commercial reality. The hormonal approach is based on suppression of pituitary gonadotropin secretion resulting in a reversible reduction in spermatogenesis with azoospermia in all men being the ultimate aim. Without stimulation by luteinising hormone from the pituitary, testicular testosterone production also ceases. Therefore, androgen administration to restore physiological levels is an essential component of all male hormonal contraceptive regimes. Male hormonal contraceptives can consist of testosterone alone, or either a progestogen or gonadotropin-releasing hormone antagonist with 'add-back' testosterone. This article reviews the current state of progress in this field.

  19. Molecular Cloning of Diapause Hormone Analog in Helicoverpa assulta%烟实夜蛾类滞育激素基因的分子克隆

    赵静雅; 张天翼; 徐卫华; 康乐


    根据烟实夜蛾(Helicoverpa assulta)的性信息素合成激活肽基因序列设计引物,以烟实夜蛾基因组DNA为模板进行PCR扩增,得到665 bp的特异性片段.该片段经过同源比较和活性测定,证实烟实夜蛾的基因组中存在类滞育激素基因.烟实夜蛾的类滞育激素是一个由24个氨基酸组成的神经肽,在第4和第5个氨基酸之间,插入了一个482 bp的内含子.进一步的分析表明,该神经肽在蛹期的食道下神经节中表达.%Diapause hormone (DH) is a neurohormone which is secreted from suboesophageal ganglion and responsi-ble for induction of enbryonic diapause in Bombyx mori. Here, using bioassay, we present evidence that Has-SGNP Ⅰ ,which clearly exhibited diapause egg inducing activity as does Bom-DH, is likely to be DH. We reported the molecularcharacterization of the Helicoverpa assulta diapause hormone analog by polymerase chain reaction. A 665 bp fragment con-taining the entire DH-like gene was isolated and characterized. DH-like gene comprised two exons interspersed by a singleintron, and the consensus sequence for splicing junction is identified at the exon/intron boundary. The result shows thatDH-like gene is localized in the genome of Helicoverpa assulta.

  20. Diapause hormone in the Helicoverpa/Heliothis complex: A review of gene expression, peptide structure and activity, analog and antagonist development, and the receptor.

    Zhang, Qirui; Nachman, Ronald J; Denlinger, David L


    This review summarizes recent studies focusing on diapause hormone (DH) in the Helicoverpa/Heliothis complex of agricultural pests. Moths in this complex overwinter in pupal diapause, a form of developmental arrest used to circumvent unfavorable seasons. DH was originally reported in the silkmoth Bombyx mori, a species that relies on DH to induce an embryonic diapause. But, in the case of Helicoverpa/Heliothis, levels of dh transcripts and DH peptides are more abundant in nondiapausing pupae than in diapausing individuals, and DH effectively terminates diapause within a specific temperature range. A structure activity relationship study indicated that the active core of DH is the C-terminal hepta-peptide, LWFGPRLa. We designed and synthesized a first generation of DH agonists and identified two agonists (PK-2Abf and PK-Etz) that were nearly 50- and 13-fold more potent than the native hormone. These studies revealed two structural characteristics of DH and its agonists that are essential for interaction with the receptor: a trans-Pro configuration to form a type I β-turn and a hydrophobic moiety involved in ligand binding. Modification of DH at the active core yielded a potent DH antagonist (DH-Jo, acetyl-GLWA[Jo]RLa) as well as an agonist (DH-2Abf-K). Three compounds (Decyl-1963, Dodecyl-1967, Heptyl-1965) were identified as agents capable of penetrating the cuticle of young pupae and thereby preventing the entry into diapause. DH receptor cDNA was cloned and an effective in vitro high throughput screen system was established for future use. This work sets the stage for further development of DH analogs and antagonists that have the potential to disrupt insect diapause as a tool for pest management.

  1. Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation

    Frokjaer, Vibe Gedsoe; Pinborg, Anja; Holst, Klaus Kähler;


    serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention. METHODS......BACKGROUND: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised.......6 ± 2.2) and at follow-up (16.2 ± 2.6 days after intervention start). RESULTS: Sex hormone manipulation with GnRHa significantly triggered subclinical depressive symptoms within-group (p = .003) and relative to placebo (p = .02), which were positively associated with net decreases in estradiol levels (p...

  2. Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation.

    Chang, Katherine; Merideth, Melissa A; Stratton, Pamela


    There is a growing population of women who have or will undergo hematopoietic stem cell transplant for a variety of malignant and benign conditions. Gynecologists play an important role in addressing the gynecologic and reproductive health concerns for these women throughout the transplant process. As women undergo cell transplantation, they should avoid becoming pregnant and are at risk of uterine bleeding. Thus, counseling about and implementing hormonal treatments such as gonadotropin-releasing hormone agonists, combined hormonal contraceptives, and progestin-only methods help to achieve therapeutic amenorrhea and can serve as contraception during the peritransplant period. In this commentary, we summarize the timing, risks, and benefits of the hormonal options just before, during, and for the year after hematopoietic stem cell transplantation.

  3. Enhancing male sexual success in a lekking fly (Anastrepha suspensa Diptera: Tephritidae) through a juvenile hormone analog has no effect on adult mortality.

    Pereira, Rui; Sivinski, John; Teal, Peter; Brockmann, Jane


    While defending lek-territories, male Anastrepha suspensa (Loew) produce chemical, acoustic and visual courtship signals. In the laboratory and under semi-natural conditions, topical application of the juvenile hormone analog methoprene doubles pheromone production and subsequently doubles sexual success. However, sexual signals and interactions are likely to be physiologically expensive and so result in higher male mortality. Comparison of males kept in isolation for 35 days, but provided daily with a potential mate or a rival male, revealed that both male- and female-interactors shortened focal-male lifespan. In addition, focal males were either treated with methoprene or not, then either provided with protein in their sucrose-based diet or not. Protein proved to similarly double sexual success and also resulted in longer male life spans in all of the interactor-categories. However, there was no evidence that methoprene induced hypersexuality resulted in higher rates of mortality, i.e., the longevity of males treated with methoprene did not significantly differ from untreated males in the same interactor/diet categories. This apparent lack of costs to a putatively sexually selected signal is unexpected but presents an opportunity to increase the sexual competence of sterile flies with few consequences to their survival following mass-release. Published by Elsevier Ltd.

  4. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.

    Alexandra Mangili

    Full Text Available Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT in human immunodeficiency virus (HIV-infected patients with lipodystrophy.1 To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF or the National Cholesterol Education Program (MetS-NCEP and the Framingham Risk Score (FRS, as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2 To explore the characteristics of patients who reached a threshold of VAT 1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively. No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI and baseline VAT (95% confidence interval [CI] 2.03; 7.44.Individuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo.

  5. Effect of transfer of one or two in vitro-produced embryos and post-transfer administration of gonadotropin releasing hormone on pregnancy rates of heat-stressed dairy cattle.

    Franco, M; Block, J; Jousan, F D; de Castro e Paula, L A; Brad, A M; Franco, J M; Grisel, F; Monson, R L; Rutledge, J J; Hansen, P J


    Pregnancy rates following transfer of an in vitro-produced (IVP) embryo are often lower than those obtained following transfer of an embryo produced by superovulation. The purpose of the current pair of experiments was to examine two strategies for increasing pregnancy rates in heat stressed, dairy recipients receiving an IVP embryo. One method was to transfer two embryos into the uterine horn ipsilateral to the CL, whereas the other method involved injection of GnRH at Day 11 after the anticipated day of ovulation. In Experiment 1, 32 virgin crossbred heifers and 26 lactating crossbred cows were prepared for timed embryo transfer by being subjected to a timed ovulation protocol. Those having a palpable CL were randomly selected to receive one (n = 31 recipients) or two (n = 27 recipients) embryos on Day 7 after anticipated ovulation. At Day 64 of gestation, the pregnancy rate tended to be higher (P = 0.07) for cows than for heifers. Heifers that received one embryo tended to have a higher pregnancy rate than those that received two embryos (41% versus 20%, respectively) while there was no difference in pregnancy rate for cows that received one or two embryos (57% versus 50%, respectively). Pregnancy loss between Day 64 and 127 only occurred for cows that received two embryos (pregnancy rate at Day 127=17%). Between Day 127 and term, one animal (a cow with a single embryo) lost its pregnancy. There was no difference in pregnancy rates at Day 127 or calving rates between cows and heifers, but females that received two embryos had lower Day-127 pregnancy rates and calving rates than females that received one embryo (P cows were synchronized for timed embryo transfer as in Experiment 1. Cows received a single embryo in the uterine horn ipsilateral to the ovary containing the CL and received either 100 microg GnRH or vehicle at Day 11 after anticipated ovulation (i.e. 4 days after embryo transfer). There was no difference in pregnancy rate for cows that received the GnRH or vehicle treatment (18% versus 17%, respectively). In conclusion, neither unilateral transfer of two embryos nor administration of GnRH at Day 11 after anticipated ovulation improved pregnancy rates of dairy cattle exposed to heat stress.

  6. 1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study

    Al Humaidan, Peter Samir Heskjær; Ejdrup Bredkjaer, Helle; Westergaard, Lars Grabow


    OBJECTIVE: To prospectively assess the reproductive outcome with a small bolus of hCG administered on the day of oocyte retrieval after ovulation induction with a GnRH agonist (GnRHa). DESIGN: Prospective, randomized trial. SETTING: Three hospital-based IVF clinics. PATIENT(S): Three hundred five...

  7. 促性腺激素释放激素受体的结构及其生物学功能%The structure and biological functions of gonadotropin-releasing hormone receptor

    肖杰文; 李学伟; 朱砺



  8. The Structure and Biological Functions of Gonadotropin-releasing Hormone (GnRH)%促性腺激素释放激素的结构及其生物学功能

    叶丹; 潘建伟; 廖鸣娟; 张志和; 朱睦元



  9. The molecular multiplicity and function of gonadotropin-releasing hormone and its receptor in vertebrate%脊椎动物GnRH肽的分子多态性和功能

    黎双飞; 胡炜; 胡章立; 朱作言



  10. The Effects of Gonadotropin Releasing Hormone Analogues on Ovarian Cancer and Ovarian Function Protection%促性腺激素释放激素类似物与卵巢癌和卵巢功能保护




  11. Effects of intramuscular injections of vitamin E-selenium and a gonadotropin releasing hormone analogue (GnRHa) on reproductive performance and blood metabolites of post-molt male broiler breeders

    Ahmad Hezarjaribi; Vahid Rezaeipour; Rohullah Abdollahpour


    Objective: To investigate the effects of intramuscular injection of vitamin E-selenium and a GnRH analogue (GnRHa) on reproductive performance and serum biochemical parameters in post-molt male broiler breeders. Methods: A total of 32 ROSS 308 male broiler breeders (60 weeks of age) were induced to molt and then were randomly distributed into four groups: group 1 (control) without any injection, group 2 subjected to intramuscular of 0.1 mL/kg body weight of vitamin E-selenium, group 3 subj...

  12. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles

    Lin, Ming-Huei; Wu, Frank Shao-Ying; Lee, Robert Kuo-Kuang; Li, Sheng-Hsiang; Lin, Shyr-Yeu; Hwu, Yuh-Ming


    ...) agonist and human chorionic gonadotropin (hCG) can improve the live-birth rate for normal responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles...

  13. Gonadotropin-releasing hormone (GnRH) agonist triptorelin inhibits estradiol-induced serum response element (SRE) activation and c-fos expression in human endometrial, ovarian and breast cancer cells.

    Gründker, Carsten; Günthert, Andreas R; Hellriegel, Martin; Emons, Günter


    The majority of human endometrial (>80%), ovarian (>80%) and breast (>50%) cancers express GnRH receptors. Their spontaneous and epidermal growth-factor-induced proliferation is dose- and time-dependently reduced by treatment with GnRH and its agonists. In this study, we demonstrate that the GnRH agonist triptorelin inhibits estradiol (E2)-induced cancer cell proliferation. The proliferation of quiescent estrogen receptor alpha (ER alpha)-/ER beta-positive, but not of ER alpha-negative/ER beta-positive endometrial, ovarian and breast cancer cell lines, was significantly stimulated (P<0.001) (ANOVA) after treatment with E2 (10(-8) M). This effect was time- and dose-dependently antagonized by simultaneous treatment with triptorelin. The inhibitory effect was maximal at 10(-5) M concentration of triptorelin (P<0.001). In addition, we could show that, in ER alpha-/ER beta-positive cell lines, E2 induces activation of serum response element (SRE) and expression of the immediate early-response gene c-fos. These effects were blocked by triptorelin (P<0.001). E2-induced activation of estrogen-response element (ERE) was not affected by triptorelin. The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.

  14. Effect of investigational kisspeptin/metastin analog, TAK-683, on luteinizing hormone secretion at different stages of the luteal phase in goats.

    Rahayu, Larasati Puji; El Behiry, Mohammed; Endo, Natsumi; Tanaka, Tomomi


    This study aimed to examine the response of luteinizing hormone (LH) secretion and ovarian steroid profile to TAK-683, an investigational metastin/kisspeptin analog, through treatment during different stages of the luteal phase in goats. Nine cycling Shiba goats (4.4 ± 2.3 years old) were assigned to early luteal phase (ELP, n = 4), mid-luteal phase (MLP, n = 4), and control (n = 5) groups. The ELP and MLP groups were administered 50 µg of TAK-683 intravenously on either day 5 or between days 7-14 after ovulation, respectively. The control group received vehicle between days 7-14 after ovulation. Blood samples were collected at 10-min (2-6 h), 2-h (6-24 h), and 24-h (24-96 h) intervals after treatment. Significant increases in plasma LH concentration were detected during the periods of 3 to 5 h and 2 to 5 h in the ELP and MLP groups, respectively. Estradiol concentrations continuously increased with the rise of basal LH secretion after TAK-683 treatment in two goats of the ELP group with a surge-like release of LH, but not in the goats without LH surge, i.e. the MLP and control group ones. Plasma progesterone concentration and the lengths of estrous cycle in all groups did not change significantly from the time before and after treatment. Present findings indicate that the responses of LH and ovarian steroids to treatment with TAK-683 depend on the stage of the luteal phase of the estrous cycle. We suggest that the stimulatory effects of TAK-683 on LH secretion are reduced in the process leading to the mid-luteal phase in cycling goats.

  15. Hormonal treatment and estrus synchronization in cows: A mini-review

    Ashit Kumar Paul


    Full Text Available Perfect detection of estrus is crucial for good husbandry practice of cow. Estrus synchronization is the alternative strategy to bypass the critical problem of estrus detection. Synchronization program allows fixed timed artificial inseminations (FTAI to evade the estrus detection. The most recently developed programs include protocols for re-synchronization following first or subsequent inseminations. These re-synchronization protocols may involve selected forms of hormonal intervention during the diestrus and pro-estrus periods following FTAI, or following pregnancy diagnosis by ultrasound from 28 days after FTAI. Almost all programs involve strategically timed treatment of prostaglandin F2α (PGF and gonadotropin releasing hormone (GnRH. Treatment of an estradiol ester and progesterone supplementation per vaginum may be included in some programs. The basic program is the “Ovsynch” regimen. This mini-review discusses a number of key points related to external hormonal stimulation on ovarian follicular wave to improve pregnancy rate following timed AI.

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

    Alun L Edwards


    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.

  17. Hormonal parameters in incidental varicoceles and those causing infertility.

    Hudson, R W; Perez-Marrero, R A; Crawford, V A; McKay, D E


    The gonadotropin responses to a 4-hour infusion of gonadotropin-releasing hormone (GnRH), the prolactin (PRL) responses to a bolus injection of thyrotropin-releasing hormone (TRH), and seminal plasma dihydrotestosterone (DHT) levels were assessed before and 6 to 12 months after varicocelectomy was performed in 56 infertile men with varicoceles and sperm densities less than 30 X 10(6)/ml. The men were divided into four groups, determined by their sperm densities and hormonal parameters. Groups I (18 men) and II (12 men) had sperm densities less than 10 X 10(6)/ml, and groups III (16 men) and IV (10 men) had sperm densities of 11 to 30 X 10(6)/ml. The men from groups I and III had excessive preoperative gonadotropin and PRL responses, and lower-than-normal seminal plasma DHT levels. The men in groups II and IV had normal hormonal values. After operation, 12 of the men from group I and 11 from group II had improvements in seminal and hormonal parameters. The other men in these two groups and all of the men in groups II and IV had no changes in seminal and hormonal parameters after operation. This study indicates that an assessment of these hormonal parameters may be useful in predicting which men with varicoceles are likely to have an improvement in sperm density after varicocele repair.

  18. Hormonal correlates of acne and hirsutism.

    Lucky, A W


    Acne is a multifactorial disorder reflecting the role of infection, abnormal keratinization and immunologic reaction, as well as hormonal influences, on the pilosebaceous unit. Clinical studies have correlated elevated levels of androgens, originating in both the adrenal glands and ovaries, with acne. These include total and free testosterone, delta 4-androstenedione, dehydroepiandrosterone and its sulfate, and low levels of sex hormone binding globulin. The pathogenesis of acne initiation in childhood has been linked to rising serum levels of dehydroepiandrosterone sulfate. Hirsutism has been more directly correlated with increased levels of serum androgens, notably free testosterone. Underlying causes of elevated androgens in both disorders include very rare tumors, partial or late-onset forms of congenital adrenal hyperplasia, developmental adrenal abnormalities and, most commonly, polycystic ovary syndrome. Early acne treatment may include topical benzoyl peroxide, antibiotics, and tretinoin. More severe disease can be treated systemically (with antibiotics and/or isotretinoin). Very-low-dose corticosteroids can be used to eliminate the adrenal component of hyperandrogenism. Oral contraceptives, especially those that contain low-androgenic progestins, can reduce excessive androgens from any source and specifically suppress the ovary in polycystic ovary syndrome. Gonadotropin-releasing hormone agonists, with or without estrogen supplementation, and systemic or topical antiandrogens may play a more important role in the future.

  19. Influence of GnRH analogue on body mass index in girls with precocious puberty: a prospective study

    Heshmat Moaieri


    Conclusion: Gonadotropin-releasing hormone analog (GnRHa therapy in central precocious puberty (CPP is safe for BMI and increasing of BMI is not significant, long- term follow-up study is required to elucidate whether GnRHa treatment affects adult obesity. Using growth hormone concomitantly, the effect on increasing height is significant.

  20. Endometriosis

    ... including birth control pills, progestin -only medications, and gonadotropin-releasing hormone agonists . Hormonal medications help slow the growth of ... egg travels from the ovary to the uterus. Gonadotropin-Releasing Hormone Agonists: Medical therapy used to block the effects ...

  1. Dysmenorrhea: Painful Periods

    ... or the hormonal intrauterine device can be tried. Gonadotropin-releasing hormone agonists are another type of medication that may ... that form in the muscle of the uterus. Gonadotropin-releasing Hormone Agonists: Medical therapy used to block the effect ...

  2. Sex hormone manipulation slows reaction time and increases labile mood in healthy women

    Stenbæk, D. S.; Fisher, P. M.; Budtz-Jørgensen, E.


    BACKGROUND: Women show increased risk of depressive symptoms in life phases where ovarian steroid hormone levels fluctuate or decline rapidly. The risk mechanisms may include changes in mental state and affective cognition possibly mediated by serotonergic neurotransmission. METHODS......: In a randomized controlled double-blinded trial, 61 healthy women (mean age 24.3±4.9 years) were tested with measures of affective verbal memory, reaction time, mental distress, and serotonin transporter binding at baseline and at follow-up after receiving gonadotropin-releasing hormone agonist (GnRHa) or placebo...... intervention. Women also reported daily mood profiles during intervention. We tested direct effects of intervention and indirect effects through changes in serotonin transporter binding on verbal affective memory, simple reaction time and self-reported measures of mental distress, and further effects of Gn...

  3. Abiraterone acetate for prostate cancer: a new era of hormonal therapies

    Emmanuel S Antonarakis


    @@ Therapies targeting the androgen receptor (AR) axis have constituted the Holy Grail in the management of advanced prostate cancer for seven decades.1 These hormonal therapies have traditionally taken two main forms: those that suppress gonadal androgen synthesis (e.g.,the gonadotropin releasing hormone agonists/antagonists,such as leuprolide),and those that inhibit the AR directly (e.g.,the anti-androgens,such asbicalutamide).However,although the vast majority of patients with prostate cancer initially respond favorably to androgen-ablative therapies (manifested by tumor regressions and symptomatic improvements),all patients will eventually develop further disease progression after a median of 18-24 months.This transformed disease state,known as castration-resistant prostate cancer (CRPC),is invariably fatal.

  4. Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa

    Li, Shizhong; Hauser, Frank; Skadborg, Signe K.


    Most multicellular animals belong to two evolutionary lineages, the Proto- and Deuterostomia, which diverged 640-760 million years (MYR) ago. Neuropeptide signaling is abundant in animals belonging to both lineages, but it is often unclear whether there exist evolutionary relationships between...... the neuropeptide systems used by proto- or deuterostomes. An exception, however, are members of the gonadotropin-releasing hormone (GnRH) receptor superfamily, which occur in both evolutionary lineages, where GnRHs are the ligands in Deuterostomia and GnRH-like peptides, adipokinetic hormone (AKH), corazonin......, and AKH/corazonin-related peptide (ACP) are the ligands in Protostomia. AKH is a well-studied insect neuropeptide that mobilizes lipids and carbohydrates from the insect fat body during flight. In our present paper, we show that AKH is not only widespread in insects, but also in other Ecdysozoa...

  5. Lunar Analog

    Cromwell, Ronita L.


    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  6. Development of gonadotropes may involve cyclic transdifferentiation of growth hormone cells.

    Childs, G V


    The cyclic rise in expression of anterior pituitary gonadotropins coincides with the appearance of cells sharing gonadotropic and somatotropic phenotypes. To learn more about possible factors that regulate the origin of this cell type, we studied the time of appearance of cells that co-expressed growth hormone (GH) and gonadotropins and estrogen receptors during the estrous cycle and compared this timing with known changes in regulatory hormones or their receptors. The first event in this cell population is an increase in expression of estrogen receptor (ER)beta by GH cells from estrus to metestrus suggesting that estrogen may mediate this early change. Expression of GH mRNA rises rapidly from metestrus to mid-cycle. The rise is seen first in GH cells and then in cells with luteinizing hormone (LH) antigens. These data suggest that, early in the cycle, cells bearing GH and growth hormone releasing hormone (GHRH) receptors begin to produce LH and gonadotropin releasing hormone (GnRH) receptors. Early in proestrus, there is an increase in cells with GH and follicle-stimulating hormone (FSH) suggesting that this set of multipotential cells develops later than GH-LH cells. This fits with earlier studies showing the later rise in expression of FSH mRNA. Collectively these data suggest that the anterior pituitary contains a subset of GH cells that have the capacity to respond to multiple releasing hormones and support more than one system.

  7. Semaphorin Signaling in the Development and Function of the Gonadotropin Hormone-Releasing Hormone (GnRH System

    Andrea eMessina


    Full Text Available The semaphorin proteins are among the best-studied families of guidance cues, contributing to morphogenesis and homeostasis in a wide range of tissue types. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors are capable to mediate signaling by semaphorins. These guidance proteins were originally identified as growth cone collapsing factors or as inhibitory signals, crucial for nervous system development. Since those seminal discoveries, the list of functions of semaphorins has rapidly grown. Over the past few years, a growing body of data indicates that semaphorins are involved in the regulation of the immune and vascular systems, in tumor growth/cancer cell metastasis and in neural circuit formation. Recently there has been increasing emphasis on research to determine the potential influence of semaphorins on the development and homeostasis of hormone systems and how circulating reproductive hormones regulate their expression and functions. Here, we focus on the emerging role of semaphorins in the development, differentiation and plasticity of unique neurons that secrete gonadotropin-releasing hormone (GnRH, which are essential for the acquisition and maintenance of reproductive competence in all vertebrates. Genetic evidence is also provided showing that insufficient semaphorin signaling contributes to some forms of reproductive disorders in humans, characterized by the reduction or failure of sexual competence.Finally, we will review some studies with the goal of highlighting how the expression of semaphorins and their receptors might be regulated by gonadal hormones in physiological and pathological conditions.

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

    Erika eComasco


    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

  9. Gonadotropin-inhibitory hormone reduces sexual motivation but not lordosis behavior in female Syrian hamsters (Mesocricetus auratus)

    Piekarski, David J; Zhao, Sheng; Jennings, Kimberly J


    Reproductive success is maximized when female sexual motivation and behavior coincide with the time of optimal fertility. Both processes depend upon coordinated hormonal events, beginning with signaling by the gonadotropin-releasing hormone (GnRH) neuronal system. Two neuropeptidergic systems...... with GnIH or saline. The effect of GnIH on sexual motivation, vaginal scent marking, and lordosis was examined. Following mating, FOS activation was quantified in brain regions implicated in the regulation of female sexual behavior. Intracerebroventricular administration of GnIH reduced sexual motivation...... and kisspeptin cell activation. Together, these data point to GnIH as an important modulator of female proceptive sexual behavior and motivation, independent of downstream alterations in sex steroid production....

  10. Central administration of growth hormone-releasing hormone triggers downstream movement and schooling behavior of chum salmon (Oncorhynchus keta) fry in an artificial stream.

    Ojima, Daisuke; Iwata, Munehico


    Anadromous salmonids migrate downstream to the ocean (downstream migration). The neuroendocrine mechanism of triggering the onset of downstream migration is not well known. We investigated the effects of 14 chemicals, including neuropeptides, pineal hormones, neurotransmitters, and neuromodulators (growth hormone-releasing hormone: GHRH, thyrotropin-releasing hormone, corticotropin-releasing hormone: CRH, gonadotropin-releasing hormone, melatonin, N-acetyl serotonin, serotonin, beta-endorphin, enkephalin, dopamine, norepinephrine, epinephrine, acetylcholine, and histamine) on the onset of downstream migration in chum salmon (Oncorhynchus keta) fry. We defined downstream migration as a downstream movement (negative rheotaxis) with schooling behavior and counted the number of downstream movements and school size in experimental circulation tanks. An intracerebroventricular injection of GHRH, CRH, melatonin, N-acetyl serotonin, or serotonin stimulated the number of downstream movements. However, GHRH was the only chemical that also stimulated an increase in schooling behavior. These results suggest that CRH, melatonin, N-acetyl serotonin, and serotonin are involved in the stimulation of downstream movement in chum salmon, while GHRH stimulates both downstream movement and schooling behavior.

  11. Synthesis of human pancreatic growth hormone-releasing factor and two omission analogs by segment-coupling method in aqueous solution

    Blake, J.; Westphal, M.; Li, C.H. (Laboratory of Molecular Endocrinology, University of California, San Francisco, USA)


    The human growth hormone-releasing factor (GRF) peptides (GlyS/sup 15/)-GRF-(1-15) (IV), trifluoroacetyl-GRF-(20-44) (VI), trifluoroacetyl-GRF-(18-44) (VIII), and trifluoroacetyl-GRF-(16-44) (X) were synthesized by the solidphase method. Each of the peptides was reacted with citraconic anhydride and the trifluoroacetyl group was removed by reaction with 10% hydrazine in water. The citraconylated GRF-(1-15) peptide was coupled to the (20-44), (18-44) or (16-44) peptides by reaction with silver nitrate/N-hydroxysuccinimide to give GRF-(1-15)-(20-44) (XII), GRF-(1-15)-(18-44) (XIII), or GRF-(1-44), respectively. GRF-(1-44) was shown to stimulate the release of rat growth hormone from rat pituitary cells with an ED/sub 50/=8.8 x 10/sup -11/M. Peptides XII and XIII were inactive, either as agonists or as antagonists of the action of GRF-(1-44).

  12. 腹腔注射LHRH-A对黑鲷生长激素及其受体的影响%Effects of Luteinizing Hormone-releasing Hormone Analogue Injection on Growth Hormone and Its Receptor in Black Seabream

    邓利; 林浩然


    以海水硬骨鱼类黑鲷为研究对象,腹腔注射溶于生理盐水的促性腺激素,释放激素(gonadotropin-releasing hormone,GnRH)的类似物(analogue of luteinizing hormone- releasing hormone,LHRH-A),对照组注射生理盐水.24 h后注射LHRH-A组黑鲷血清生长激素(growth hormone,GH)水平显著高于对照组(p<0.05),于36 h又恢复到对照组水平.注射LHRH-A组肝脏生长激素受体(growth hormone receptor,GHR)及GHR mRNA均与对照组无显著差异.结果表明,腹腔注射LHRH-A刺激了处于性腺成熟期黑鲷GH的分泌,但对黑鲷肝脏GHR及其基因表达无明显影响.

  13. Analog computing

    Ulmann, Bernd


    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  14. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

    N.S. Macklon (Nick); M.J.C. Eijkemans (René); M. Ludwig (Michael); R.E. Felberbaum; K. Diedrich; S. Bustion; E. Loumaye; B.C.J.M. Fauser (Bart); N.G.M. Beckers (Nicole)


    textabstractReplacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because o

  15. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Kazuyoshi eTsutsui


    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.

  16. Remating behavior in Anastrepha fraterculus (Diptera: Tephritidae) females is affected by male juvenile hormone analog treatment but not by male sterilization.

    Abraham, S; Liendo, M C; Devescovi, F; Peralta, P A; Yusef, V; Ruiz, J; Cladera, J L; Vera, M T; Segura, D F


    The sterile insect technique (SIT) has been proposed as an area-wide method to control the South American fruit fly, Anastrepha fraterculus (Wiedemann). This technique requires sterilization, a procedure that affects, along with other factors, the ability of males to modulate female sexual receptivity after copulation. Numerous pre-release treatments have been proposed to counteract the detrimental effects of irradiation, rearing and handling and increase SIT effectiveness. These include treating newly emerged males with a juvenile hormone mimic (methoprene) or supplying protein to the male's diet to accelerate sexual maturation prior to release. Here, we examine how male irradiation, methoprene treatment and protein intake affect remating behavior and the amount of sperm stored in inseminated females. In field cage experiments, we found that irradiated laboratory males were equally able to modulate female remating behavior as fertile wild males. However, females mated with 6-day-old, methoprene-treated males remated more and sooner than females mated with naturally matured males, either sterile or wild. Protein intake by males was not sufficient to overcome reduced ability of methoprene-treated males to induce refractory periods in females as lengthy as those induced by wild and naturally matured males. The amount of sperm stored by females was not affected by male irradiation, methoprene treatment or protein intake. This finding revealed that factors in addition to sperm volume intervene in regulating female receptivity after copulation. Implications for SIT are discussed.

  17. Involvement of hormones in olfactory imprinting and homing in chum salmon.

    Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko


    The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

  18. Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

    Cao, Mengxi; Chen, Ji; Peng, Wei; Wang, Yaping; Liao, Lanjie; Li, Yongming; Trudeau, Vance L; Zhu, Zuoyan; Hu, Wei


    To study the complex interaction between growth and reproduction we have established lines of transgenic common carp (Cyprinus carpio) carrying a grass carp (Ctenopharyngodon idellus) growth hormone (GH) transgene. The GH-transgenic fish showed delayed gonadal development compared with non-transgenic common carp. To gain a better understanding of the phenomenon, we studied body growth, gonad development, changes of reproduction related genes and hormones of GH-transgenic common carp for 2years. Over-expression of GH elevated peripheral gh transcription, serum GH levels, and inhibited endogenous GH expression in the pituitary. Hormone analyses indicated that GH-transgenic common carp had reduced pituitary and serum level of luteinizing hormone (LH). Among the tested genes, pituitary lhβ was inhibited in GH-transgenic fish. Further analyses in vitro showed that GH inhibited lhβ expression. Localization of ghr with LH indicates the possibility of direct regulation of GH on gonadotrophs. We also found that GH-transgenic common carp had reduced pituitary sensitivity to stimulation by co-treatments with a salmon gonadotropin-releasing hormone (GnRH) agonist and a dopamine antagonist. Together these results suggest that the main cause of delayed reproductive development in GH transgenic common carp is reduced LH production and release.

  19. Broodstock management and hormonal manipulations of fish reproduction.

    Mylonas, Constantinos C; Fostier, Alexis; Zanuy, Silvia


    Control of reproductive function in captivity is essential for the sustainability of commercial aquaculture production, and in many fishes it can be achieved by manipulating photoperiod, water temperature or spawning substrate. The fish reproductive cycle is separated in the growth (gametogenesis) and maturation phase (oocyte maturation and spermiation), both controlled by the reproductive hormones of the brain, pituitary and gonad. Although the growth phase of reproductive development is concluded in captivity in most fishes-the major exemption being the freshwater eel (Anguilla spp.), oocyte maturation (OM) and ovulation in females, and spermiation in males may require exogenous hormonal therapies. In some fishes, these hormonal manipulations are used only as a management tool to enhance the efficiency of egg production and facilitate hatchery operations, but in others exogenous hormones are the only way to produce fertilized eggs reliably. Hormonal manipulations of reproductive function in cultured fishes have focused on the use of either exogenous luteinizing hormone (LH) preparations that act directly at the level of the gonad, or synthetic agonists of gonadotropin-releasing hormone (GnRHa) that act at the level of the pituitary to induce release of the endogenous LH stores, which, in turn act at the level of the gonad to induce steroidogenesis and the process of OM and spermiation. After hormonal induction of maturation, broodstock should spawn spontaneously in their rearing enclosures, however, the natural breeding behavior followed by spontaneous spawning may be lost in aquaculture conditions. Therefore, for many species it is also necessary to employ artificial gamete collection and fertilization. Finally, a common question in regards to hormonal therapies is their effect on gamete quality, compared to naturally maturing or spawning broodfish. The main factors that may have significant consequences on gamete quality-mainly on eggs-and should be considered

  20. Putative relationship between hormonal status and serum pyrrolidone carboxypeptidase activity in pre- and post- menopausal women with breast cancer.

    Carrera-González, María del Pilar; Ramírez-Expósito, María Jesús; Dueñas, Basilio; Martínez-Ferrol, Julia; Mayas, María Dolores; Martínez-Martos, José Manuel


    In breast cancer, hormonal changes are rather constant in post-menopausal women since they tend to vary only over long time spans. However, in pre-menopausal women, the development of breast cancer is associated with hormonal physiological variations. The aim of the present work was to analyse the changes in circulating levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in pre- and post-menopausal women that were healthy or with breast cancer, and their connection to serum pyrrolidone carboxypeptidase (Pcp) activity. We observed significant changes in the hormonal profile in post-menopausal women with breast cancer compared to the control group. In pre-menopausal women, we found significant changes in circulating GnRH levels with respect to the healthy group. Our present results support the existence of neuroendocrine misregulation that could be involved in tumour progression, with Pcp being a potentially new pharmacological target in breast cancer treatments.

  1. Analog earthquakes

    Hofmann, R.B. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)


    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  2. Hormone signaling pathways as treatment targets in renal cell cancer (Review).

    Czarnecka, Anna M; Niedzwiedzka, Magdalena; Porta, Camillo; Szczylik, Cezary


    Epidemiological, clinical, biochemical and genetic research has revealed that renal cell cancer (RCC) etiology is hormone-related. It was shown that hormone receptors are abnormally expressed in RCC cells. Abnormal endocrine stimulation also plays a significant role in RCC pathophysiology. Cellular proliferation, migration, angiogenesis, and drug resistance in RCC is modulated by para- and autocrine hormonal stimulation. In particular, RCC overexpression of gonadotropin-releasing hormone and its receptor was reported. On the contrary, corticotropin releasing hormone was reported to inhibit RCC cell proliferation and regulate angiogenesis. Overexpression of luteinizing hormone also promotes RCC tumor angiogenesis. Estrogen receptor α overexpression increases the transcriptional factor activity of hypoxia inducible factor HIF-1α, but estrogen receptor β has a cancer suppressive role. Glucocorticoid receptors and androgen receptor are markers of indolent RCC and assigned tumor suppressive activity. Proopiomelanocortin is upregulated in VHL-mutated renal cell carcinoma via Nur77 transcription factor signaling. In RCC, follicle-stimulating hormone receptor promotes angiogenesis and metastatic formation via VEGF release. Mineralocorticoid receptor overexpression promotes cell survival and increases RCC cell proliferation. Vitamin D receptor expression is downregulated or absent in RCC and differentiate subtypes of renal cell tumors. RAR-β promotes tumorigenesis but retinoic acid receptor γ expression correlates negatively with the TNM stage at diagnosis. Finally, progesterone receptor expression is negatively correlated with the cancer stage. Molecular data analysis revealed the possibility of renal cancer cell proliferation induction via hormone activated pathways. Inhibition of hormonal signaling may thus play a putative role in supportive therapies against this cancer type.

  3. Análogo de GnRH disminuye la secreción de hormona folículo estimulante (FSH en ovejas prepúberes A gonadotropin releasing hormone analogue decreases follicle stimulating hormone (FSH secretion in prepubertal female sheep

    S E Recabarren


    Full Text Available La secreción de LH y FSH depende de la liberación pulsátil de GnRH desde el hipotálamo; sin embargo, el grado de dependencia así como la relación entre los pulsos de GnRH y la secreción de FSH es menos clara. Experimentos en monos han mostrado que altas frecuencias de liberación de pulsos de GnRH estimulan preferentemente la secreción de LH, mientras que bajas frecuencias de pulsos de GnRH favorecen la secreción de FSH. Estudios sobre el control de la secreción de FSH en ovejas prepúberes son escasos. Con el objetivo de reconocer la dependencia de la secreción de FSH por parte de la GnRH, se administró un análogo de GnRH en microcápsulas de liberación lenta (Trp6-GnRH, Decapeptyl® y cuyo efecto bloqueador sobre la secreción de LH ha sido demostrado. El análogo se administró intramuscularmente cada cuatro semanas a partir de las 20 semanas de edad a cinco borregas Suffolk por tres veces. Otro grupo de ovejas prepúberes de las mismas edades recibió el vehículo. Estudios de pulsatilidad de FSH se efectuaron a las, 20, 26 y 30 semanas de edad. Se utilizó el programa Cluster para reconocer las características de la secreción pulsátil de FSH. En las borregas del grupo control no hubo cambios en las características de la secreción pulsátil de FSH entre las 20 y 30 semanas de edad. En el grupo tratado con el análogo de GnRH, las concentraciones plasmáticas de FSH disminuyeron desde 3,4±0,3 ng/mL/5h a las 20 semanas de edad hasta los 0,36±0,1 ng/mL/5h a las 30 semanas de edad (pLH and FSH secretions depend on the pulsatile secretion of GnRH from the hypothalamus. However, the grade of dependency as well as the relationship between pulses of GnRH and pulses of FSH secretion is less clear. Experiments in monkeys have shown that high GnRH pulse frequency favors LH secretion while low frequency of GnRH pulses preferentially stimulates the FSH secretion. The objective of the present work was to recognize the dependence of GnRH on the FSH secretion in prepubertal female sheep. A GnRH agonist analogue in slow release microcapsule preparation was used (Trp6-GnRH, (Decapeptyl® whose blocking effect on the LH release has been previously demonstrated. The analogue was injected intramuscularly every 4 weeks beginning at 20 weeks of age three times in five Suffolk ewe lambs. Another group of five lambs received the vehicle of Decapeptyl. Studies of FSH pulsatility were carried out at 20 (before the analogue agonist administration, 26 and 30 weeks of age. The CLUSTER program was used to identify characteristics of FSH secretion: transversal mean (ng/ml/5h, frequency of pulses (number of pulses/5h, amplitude of pulses (ng/ml and nadir (ng/ml . In the control group, FSH secretion characteristics did not change between 20 and 30 weeks of age. In the experimental group, mean FSH concentrations decreased from 3.4±0.3 ng/ml/5h at 20 weeks of age to 0.36 ±0.1 ng/mL/ 5h at 30 weeks of age (P<0,05, which was also significantly lower than in the control group of the same age. Amplitude of FSH pulses in lambs of 30 weeks of age were significantly lower than in lambs of 20 weeks of age (4.4 ± 0.5 versus 0.5 ± 0.1 ng/mL respectively, P<0.05, and lower than that exhibited by control ewe lambs of 30 weeks of age. FSH pulse frequency did not change between lambs of 20 and 30 weeks of age in either group. Results show that the GnRH analogue is able to block the FSH secretion suggesting that the FSH secretion is dependant on GnRH stimulation in prepubertal female sheep.

  4. Candidate genes associated with testicular development, sperm quality, and hormone levels of inhibin, luteinizing hormone, and insulin-like growth factor 1 in Brahman bulls.

    Fortes, Marina R S; Reverter, Antonio; Hawken, Rachel J; Bolormaa, Sunduimijid; Lehnert, Sigrid A


    Bull fertility is an important target for genetic improvement, and early prediction using genetic markers is therefore a goal for livestock breeding. We performed genome-wide association studies to identify genes associated with fertility traits measured in young bulls. Data from 1118 Brahman bulls were collected for six traits: blood hormone levels of inhibin (IN) at 4 mo, luteinizing hormone (LH) following a gonadotropin-releasing hormone challenge at 4 mo, and insulin-like growth factor 1 (IGF1) at 6 mo, scrotal circumference (SC) at 12 mo, ability to produce sperm (Sperm) at 18 mo, and percentage of normal sperm (PNS) at 24 mo. All the bulls were genotyped with the BovineSNP50 chip. Sires and dams of the bull population (n = 304) were genotyped with the high-density chip (∼800 000 polymorphisms) to allow for imputation, thereby contributing detail on genome regions of interest. Polymorphism associations were discovered for all traits, except for Sperm. Chromosome 2 harbored polymorphisms associated with IN. For LH, associated polymorphisms were located in five different chromosomes. A region of chromosome 14 contained polymorphisms associated with IGF1 and SC. Regions of the X chromosome showed associations with SC and PNS. Associated polymorphisms yielded candidate genes in chromosomes 2, 14, and X. These findings will contribute to the development of genetic markers to help select cattle with improved fertility and will lead to better annotation of gene function in the context of reproductive biology.

  5. Application of Gonadotrophin-Releasing Hormone Analogs in Malignant Gynecological Neoplasms%促性腺激素释放激素类似物在妇科恶性肿瘤中的应用



    According to its mechanisms of action, gonadotrophin-releasing hormone analogs (GnRH-A) are divided into two categories:agonist and antagonist. It has been demonstrated that 80% of ovarian and endometrial cancers express GnRH and its receptors. The anti-cancer role of GnRH-A is played either by suppressing the hypothalamic-pituitary axis or through its autocrine and paracrine systems. GnRH-A had been used in the treatment of advanced or recurrent endometrial and ovarian cancers, but the effect is no better than other second-line drugs.These days, the application of GnRH-A in the preservation of fertility and ovarian function has become increasingly popular. Besides, the use of GnRH -A in molecular targeted therapy is also promising.%根据作用机制不同,促性腺激素释放激素类似物(GnRH-A)可分为两类:激动剂和拮抗剂.研究证实,约80%的卵巢癌以及子宫内膜癌能够表达GnRH及其受体,GnRH-A通过间接抑制下丘脑-垂体-性腺轴或通过自分泌及旁分泌直接抑制肿瘤细胞的增殖.GnRH-A曾被用于治疗晚期或复发的子宫内膜癌和卵巢癌,但疗效不明显.而目前研究的热点是将GnRH-A用于保留早期子宫内膜癌患者的生育功能以及保护肿瘤化疗患者的卵巢功能.GnRH-A还可用于妇科恶性肿瘤的靶向治疗.

  6. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    Hojatollah Karimi Jashni


    Full Text Available Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH, follicular stimulating hormone (FSH, Luteinal hormone (LH, estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05. Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

  7. Effect of some hormones on reproductive performance and some

    F. T. Juma


    Full Text Available In randomized block design, 58 indigenous black mountain goats were examined for the effect of different hormonal treatments in inducing oestrus on selected biochemical characteristics of blood serum that were (aspartate transaminase, AST. Alanine transaminase ALT, Akaline phosphatase, ALP, total protein, albumin and total cholesterol. The animals were randomly assigned into four groups according to their treatment. The control group (C consisted of 10 females whereas the rest of the groups, each consisted of 12 females. The treatments included a double PGF2α (Dinoprost tromethamine intramuscular injection (5 mg at a time interval of 11 days plus an intramuscular injection of pregnant mare serum (PMSG (400I. Uand 600I. U. two days before second injection for (treatments, TI, T2 respectively. Treatment (T3 was as that of T1 except PMSG was not injected. T4 was treated as T3 plus an intramuscular injection of gonadotropin releasing hormone (GnRH (12. 5µg after 24 hours of second injection of PGF2α was added. The results indicated that oestrus was higher (P<0.05 in all treatment groups (100%, 91%, 100%, 100% respectively than that of control group (70%. There was a significant effect (P<0.05 of hormonal treatment on kidding rate in which the ratio were (116%, 115%, 75% and 83% for treatment groups respectively in comparison with 70% for control group, also there was significant effect (P<0.05 of hormonal treatment on litter size in (T3. There were significant increases in activity of AST, ALT, during late pregnancy and the first week of parturition, whereas the activity of ALP enzyme was increased during early pregnancy. The concentration of total protein, total cholesterol and albumin were increased (P<0.05 during late stage of pregnancy and then decreased during the first week after parturition. It was concluded that administrating of PGF2α to does on this synchronization regimen in the natural breeding season is desirable.

  8. The expression of several reproductive hormone receptors can be modified by perfluorooctane sulfonate (PFOS) in adult male rats.

    López-Doval, S; Salgado, R; Lafuente, A


    This study was undertaken to evaluate the possible role of several reproductive hormone receptors on the disruption of the hypothalamic-pituitary-testis (HPT) axis activity induced by perfluorooctane sulfonate (PFOS). The studied receptors are the gonadotropin-releasing hormone receptor (GnRHr), luteinizing hormone receptor (LHr), follicle-stimulating hormone receptor (FSHr), and the androgen receptor (Ar). Adult male rats were orally treated with 1.0; 3.0 and 6.0 mg of PFOS kg(-1) d(-1) for 28 days. In general terms, PFOS can modify the relative gene and protein expressions of these receptors in several tissues of the reproductive axis. At the testicular level, apart from the expected inhibition of both gene and protein expressions of FSHr and Ar, PFOS also stimulates the GnRHr protein and the LHr gene expression. The receptors of the main hormones involved in the HPT axis may have an important role in the disruption exerted by PFOS on this axis.

  9. Thyroid Hormone Upregulates Hypothalamic kiss2 Gene in the Male Nile Tilapia, Oreochromis niloticus

    Satoshi eOgawa


    Full Text Available Kisspeptin has recently been recognized as a critical regulator of reproductive function in vertebrates. During the sexual development, kisspeptin neurons receive sex steroids feedback to trigger gonadotropin-releasing hormone (GnRH neurons. In teleosts, a positive correlation has been found between the thyroid status and the reproductive status. However, the role of thyroid hormone in the regulation of kisspeptin system remains unknown. We cloned and characterized a gene encoding kisspeptin (kiss2 in a cichlid fish, the Nile tilapia (Oreochromis niloticus. Expression of kiss2 mRNA in the brain was analyzed by in situ hybridization. The effect of thyroid hormone (triiodothyronine, T3 and hypothyroidism with methimazole (MMI on kiss2 and the three GnRH types (gnrh1, gnrh2 and gnrh3 mRNA expression was analyzed by real-time PCR. Expression of thyroid hormone receptor mRNAs were analyzed in laser-captured kisspeptin and GnRH neurons by RT-PCR. The kiss2 mRNA expressing cells were seen in the nucleus of the lateral recess in the hypothalamus. Intraperitoneal administration of T3 (5µg/g body weight to sexually mature male tilapia significantly increased kiss2 and gnrh1 mRNA levels at 24 hr post injection (P < 0.001, while the treatment with an anti-thyroid, MMI (100 ppm for 6 days significantly reduced kiss2 and gnrh1 mRNA levels (P < 0.05. gnrh2, gnrh3 and thyrotropin-releasing hormone mRNA levels were insensitive to the thyroid hormone manipulations. Furthermore, RT-PCR showed expression of thyroid hormone receptor mRNAs in laser-captured GnRH neurons but not in kiss2 neurons. This study shows that GnRH1 may be directly regulated through thyroid hormone, while the regulation of Kiss2 by T3 is more likely to be indirect.

  10. L-pGlu-(2-propyl)-L-His-L-ProNH₂ attenuates 4-aminopyridine-induced epileptiform activity and sodium current: a possible action of new thyrotropin-releasing hormone analog for its anticonvulsant potential.

    Sah, N; Rajput, S K; Singh, J N; Meena, C L; Jain, R; Sikdar, S K; Sharma, S S


    L-PGlu-(2-propyl)-L-His-L-ProNH₂ (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4-aminopyridine (4-AP) containing Mg⁺²-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg⁺² (2.10±0.47 Hz) as compared with nACSF (0.12±0.08 Hz). A significant decrease in mean firing frequency (0.61±0.22 Hz), mean frequency of epileptiform events (0.03±0.02 Hz vs. 0.22±0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54±1.21 Hz vs. 8.16±0.88 Hz of 4-AP+0 Mg) was observed. A significant reduction in peak dV/dt (246±19 mV ms⁻¹ vs. 297±18 mV ms⁻¹ of 4-AP+0 Mg) and increase (1.332±0.018 ms vs. 1.292±0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration-dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 μM) depressed sodium current (15±0.5%, 50±2.6%, and 75±0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly.

  11. Effects of dietary supplementation of methionine and its hydroxy analog DL-2-hydroxy-4-methylthiobutanoic acid on growth performance, plasma hormone levels, and the redox status of broiler chickens exposed to high temperatures.

    Willemsen, H; Swennen, Q; Everaert, N; Geraert, P-A; Mercier, Y; Stinckens, A; Decuypere, E; Buyse, J


    Heat stress is known to impair performance and to induce oxidative stress in poultry. The aim of the present study was to compare the effects of dietary supplementation of dl-methionine (dl-M) or the synthetic analog 2-hydroxy-4-methylthiobutanoic acid (dl-HMTBA) on broiler growth performance, plasma hormone levels, and some oxidative stress-related parameters under conditions of chronic exposure to high temperatures (HT). From 2 to 6 wk of age, male broiler chickens were reared under either a constant temperature of 32°C until 6 wk of age or a normal temperature scheme (gradual decrease to 18°C at 5 wk of age). Chicks in both the normal and HT treatments were provided with a commercial grower diet supplemented with either 1.0 or 1.2 g/kg of dl-M or 1.0 or 1.2 g/kg of dl-HMTBA. Because there were no effects of supplement dose, data were pooled over both doses within each temperature treatment. The chronic HT treatment impaired feed intake and BW gain, but these negative effects were less pronounced when the chickens received dl-HMTBA. Exposure to HT was also associated with decreased (P chickens subjected to HT were characterized by significantly lower plasma TBA-reactive substance levels. In contrast, at 6 wk of age, plasma TBA-reactive substance levels were significantly increased by HT, but this effect was observed only for the chickens receiving dl-M and not for those receiving dl-HMTBA. High temperatures induced a significant increase in hepatic total glutathione (GSH) and oxidized GSH levels, regardless of the supplemental source. However, the hepatic ratios of reduced GSH to total GSH and reduced GSH to oxidized GSH were highest in chickens supplemented with dl-HMTBA. In conclusion, dl-HMTBA supplementation partially prevented the growth-depressing effects of chronic heat exposure compared with dl-M supplementation. It can be inferred that dl-HMTBA is more efficient in alleviating HT-induced oxidative damage because of a more favorable reduced GSH

  12. Growth Hormone

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


    Kornyat S.


    Full Text Available For the correction of reproductive function of cows with ovarian hypofunction practices use a number of hormones. Recently, to stimulate reproductive function using herbal medicines that have gonadotropic effect or stimulate secretion of steroid hormones who try to use to increase fertility. Therefore, we carried out an attempt to develop a method of regulation of reproductive function of the ovaries of cows using combination therapies that can provide effective treatment by studying the biochemical parameters of animals. The cows were divided depending on the treatment to control and two experimental groups of 5 animals in each group. Groups were formed by the following treatment regimens indicated pathology. Cows control group treated by next scheme: day 1 — intramuscular injection drug in vitro at a dose of 10 ml; day 2 —PMSG intramuscular administration of the drug at a dose of 500 IU; day 3 —intramuscular injection drug Surfahon at a dose of 50 mg. Cows from experimental group 1 was injected intramuscularly liposomal drug based on herbal (Rhodiola rosea, Salvia; Animals from second experimental group were injected intramuscularly liposomal drug based on phyto-substances (Rhodiola rosea, Salvia with gonadotropin-releasing hormone (Surfahon. Analysis of biochemical parameters of blood serum of cows with ovarian hypofunction found low concentrations of estradiol-17-β and progesterone. Between the control and experimental groups concentration of progesterone and estradiol-17-β differ within 10%, which indicates the same level of disease in all animals selected. Level carotene, ascorbic acid and cholesterol in all groups was within the physiological norm and differed slightly. It was established that the treatment of cows with hypofunction ovaries in the experimental group 1 progesterone level 7 days after treatment was 11.5, and 2 - on 41,4% (p <0,01 higher than in the control group animals, indicating that the revitalization of the

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

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


    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 (/sup 3/H)glucosamine (glycosylation) and (/sup 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 (/sup 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.

  15. Why do some adult birds skip breeding? A hormonal investigation in a long-lived bird.

    Goutte, Aurélie; Kriloff, Marion; Weimerskirch, Henri; Chastel, Olivier


    Skipping reproduction is often observed in long-lived organisms, but proximate mechanisms remain poorly understood. Since young and/or very old snow petrels (Pagodroma nivea) commonly skip breeding, we tested whether they are physiologically able to breed during the pre-laying stage. To do so, we measured the ability of known-age (11-45 years old) petrels to release luteinizing hormone (LH, a crucial driver for breeding), by injecting exogenous gonadotropin-releasing hormone (GnRH). Although young petrels exhibited low baseline LH levels, they were able to elevate LH levels after a GnRH challenge. Moreover, young and very old petrels showed a stronger decrease in LH levels after the 10 min post-GnRH injection compared with middle-aged petrels. Birds that skipped breeding were as able as breeders to release LH after a GnRH challenge, indicating that they had functional pituitaries. However, the decision to skip reproduction was linked to a strong LH decrease after the 10 min post-GnRH injection. Our result suggests that the youngest and the oldest petrels fail to maintain elevated baseline LH levels, thereby do not initiate reproductive activities. Skipping reproduction in long-lived birds probably results from age-related changes in the dynamics of the hypothalamic-pituitary-gonadal (HPG) axis function.

  16. Functional and neurophysiological evidence of the efficacy of trophic repair pharmacotherapy using an adrenocorticotrophic hormone4-9 analog in experimental allergic encephalomyelitis, an animal model of multiple sclerosis

    Gispen, W.H.; Duckers, H.J.; Dokkum, R.P. van; Verhaagen, J.; Lopes da Silva, F.H.


    Chronic experimental allergic encephalomyelitis (CEAE) is a well-established animal model for the human syndrome, multiple sclerosis. CEAE has striking histological, electrophysiological and clinical analogies with multiple sclerosis and is a valuable animal model for the preclinical pharmacotherape

  17. The characteristics of vasa gene from Japanese sea bass ( Lateolabrax japonicas) and its response to the external hormones

    Chi, Meili; Wen, Haishen; Ni, Meng; Qian, Kun; Zhang, Pei; Chai, Senhao


    The RNA helicase Vasa is an important regulator of primordial germ cell development. Its function in mature fish, especially the hormone-related differences in maturing male fish has seldom been documented. In this study, a full length cDNA sequence of the vasa gene was cloned from Japanese sea bass, Lateolabrax japonicas, and it was named jsb-vasa. Homology analysis showed that jsb-vasa was closely related to its teleost homologs. The spatial distribution of jsb-vasa indicated that it was only highly expressed in testis, showing its germ cell-specific expression pattern. During the testicular development cycle, jsb-vasa was highly expressed during early period of spermatogenesis, and reduced when spermatogenesis advanced. In addition, the jsb-vasa gene expression was significantly inhibited at 6 h, 12 h and 24 h after injecting hCG (human chorionic gonadotropin) and GnRHa (Gonadotropin-releasing hormone analogue), indicating that jsb-vasa gene may play an important role in spermatogenesis of Japanese sea bass, and be under the regulation of external sex hormones.

  18. Effect of adding a gonadotropin-releasing-hormone treatment at the beginning and a second prostaglandin F2α treatment at the end of an estradiol-based protocol for timed artificial insemination in lactating dairy cows during cool or hot seasons of the year.

    Pereira, M H C; Wiltbank, M C; Barbosa, L F S P; Costa, W M; Carvalho, M A P; Vasconcelos, J L M


    Our hypothesis was that fertility could be increased in a timed artificial insemination (TAI) protocol based on estradiol (E2) and progesterone (P4) by combining GnRH with E2-benzoate at the start of the protocol to increase circulating P4 during preovulatory follicle development and by using 2 prostaglandin F2α (PGF) treatments at the end to decrease P4 near TAI. Lactating Holstein cows (n=1,808) were randomly assigned during the cool or hot season of the year to receive TAI (d 0) following 1 of 3 treatments: (1) control: controlled internal drug-release insert + 2mg of E2-benzoate on d -11, PGF on d -4, controlled internal drug-release insert withdrawal + 1.0mg of E2-cypionate on d -2, and TAI on d 0; (2) 2PGF: identical to control protocol with addition of a second PGF treatment on d -2; (3) GnRH: identical to 2PGF protocol with addition of a 100-μg GnRH treatment on d -11. Pregnancy diagnoses were performed on d 32 and 60 after TAI. Season had major effects on many reproductive measures, with cool season greater than hot season in percentage of cows with corpus luteum (CL) at PGF (62.9 vs. 56.2%), ovulatory follicle diameter (15.7 vs. 14.8mm), expression of estrus (86.7 vs. 79.9%), ovulation following the protocol (89.7 vs. 84.3%), and pregnancies per artificial insemination (P/AI; 45.4 vs. 21.4%). The GnRH protocol increased percentage of cows with CL (control=56.9%; 2PGF=55.8%; GnRH=70.5%) and P4 at PGF (control=3.28±0.22; 2PGF=3.35±0.22; GnRH=3.70±0.21ng/mL), compared with control and 2PGF protocols. The GnRH protocol increased P/AI at the pregnancy diagnosis at 32d [37.3% (219/595)] and 60d [31% (179/595)] after TAI, compared with control [30.0% (177/604); 25.1% (145/604)], with intermediate results with 2PGF protocol [33.2% (196/609); 28.0% (164/609)]. The positive effects of GnRH treatment on P/AI were only detected during the cool season (GnRH=50.9%; 2PGF=44.2%; control=41.0%) and not during the hot season. In addition, the effect of GnRH was only observed in cows with low P4 (<3ng/mL) at the start of the protocol and not in cows that began the protocol with high P4. Furthermore, presence of CL at PGF interacted with follicle diameter such that cows with a CL at PGF had greater P/AI if they ovulated larger rather than smaller follicles near TAI. Thus, fertility to TAI can be improved by inducing ovulation at the beginning of an E2/P4-based protocol using GnRH treatment, particularly during the cool season of the year and in cows with low P4 at the start of the protocol.

  19. Prognosis Analysis of Gonadotropin-releasing Hormone Agonist Combined with Gestrinone after Laparoscopic Surgery Treatment for the Patients with Endometriosis%联合应用促性腺激素释放激素激动剂和孕三烯酮治疗子宫内膜异位症患者的预后分析



    目的:探讨腹腔镜术后联合应用促性腺激素释放激素激动剂(GnRH-a)和孕三烯酮巩固治疗子宫内膜异位症患者的临床效果,并分析其对患者卵巢功能及复发和再次妊娠的影响。方法:选取2012年1月-2014年3月在本院妇产科行腹腔镜手术治疗的子宫内膜异位症患者164例,按随机数字表法分为四组,分别为联合组38例(术后应用GnRH-a联合孕三烯酮治疗),GnRH-a组43例(术后仅应用GnRH-a治疗),孕三烯酮组47例(术后仅应用孕三烯酮治疗),对照组36例(术后应用安慰剂治疗)。比较四组的症状缓解情况、用药前后性激素水平的变化、复发及再次妊娠情况。结果:联合组、GnRH-a组、孕三烯酮组患者症状明显缓解率比较差异均无统计学意义(P>0.05),但三组均明显高于对照组,与对照组比较差异均有统计学意义(P0.05),但均明显小于孕三烯酮组,差异有统计学意义(P0.05),但均明显低于对照组,与对照组比较差异均有统计学意义(P0.05),但均明显高于孕三烯酮组,两组与孕三烯酮组比较差异均有统计学意义(P0.05);but the remission rate of three groups were significantly higher than that of control group, the differences were statistically significant(P0.05);but the recurrence rate of three groups were significantly lower than that of control group, the differences were statistically significant(P0.05),but they were significantly better than those of Gestrinone group, the differences were statistically significant(P<0.05).Conclusion: After laparoscopic surgery, the clinical efficacy and the prevention recurrence of GnRH-a combined with Gestrinone,only GnRH-a and only Gestrinone are equivalent,the effect of improving ovarian function and promoting good pregnancy outcomes of GnRH-a combined with Gestrinone are similar with GnRH-a, but better than only Gestrinone.

  20. Evolutiongry Aspects of the Structures and Functions of Gonadotropin-Releasing hormone(GnRH) and Its Receptors%促性腺激素释放激素(GnRH)结构与功能及其受体的进化发展



    促性腺激素释放激素是下丘脑分泌产生的神经激素,对脊椎动物生殖的调控起重要作用.自1971年从猪和羊的脑分离出GnRH以来,到目前GnRH家族至少已有24个类型,其中14种来自脊椎动物,10种来自无脊椎动物.除章鱼GnRH(octo GnRH)外,所有的GnRH肽都由10个氨基酸组成,其分子长度和部份氨基酸序列非常保守.每种脊椎动物都产生多种GnRH类型.无脊椎动物鉴别的10种GnRH类型、9种来自被囊类,1种是由12个氨基酸组成的章鱼GnRH.生理学研究表明GnRH和无脊椎动物的生殖功能有密切联系;此外,GnRH在一些无脊椎动物还起着性外激素的作用,刺激它们自行产卵.自克隆小鼠GnRH受体转录物以来,已在22种动物克隆32个GnRH受体cDNA,其中11种是哺乳动物,11种是其他脊椎动物.无脊椎动物只在果蝇鉴别出一种类GnRH受体.以鱼类为例,氨基酸序列分析表明鱼类的GnRH-R属于G-蛋白偶联受体家族(GPCRs)中视紫红质亚族中的β-亚群,它们由3个主要功能域组成,包括N-端细胞外功能域,7个跨膜功能域和C-端细胞质功能域.系统发生分析表明鱼类的GnRH-R主要有两个类型,即Ⅰ型和Ⅱ型;每个类型还包括2到3个亚型.编码不同的GnRH-R类型的基因,具有不同的基因结构.GnRH-R基因的表达主要集中在生殖系统及相关的器官与组织,但每种鱼类GnRH-R的不同类型与亚型在组织或细胞中的具体分布有所不同.

  1. Effects of gonadotropin releasing hormone analogues on chemotherapy-induced ovarian function damage in rats%促性腺激素释放激素类似物对化疗大鼠卵巢功能损害的干预作用

    彭萍; 杨冬梓; 郑澄宇; 莫亚勤; 何英明; 张清学


    目的 探讨促性腺激素释放激素激动剂(GnRH-a)和拮抗剂(GnRH-ant)对环磷酰胺(CTX)诱导的大鼠卵巢功能损害的干预作用.方法 将72只雌性SD大鼠随机分为6组,即对照组[腹腔注射生理盐水(NS)0.1 ml/d×11 d]、CTX组(第1天腹腔注射CTX 50 mg/kg,第2天起腹腔注射CTX 5 mg/d×10 d)、GnRH-a+NS组[GnRH-a 0.375 mg 1次深部肌内注射(估计释放量为12.5μg/d,持续28~30 d),于用药第14天左右(连续5 d观察阴道涂片均处于动情间期)开始注射NS,用药方法同对照组]、GnRH-a+CTX组(同GnRH-a+NS组注射GnRH-a后,于用药第14天左右的动情间期开始注射CTX,用药方法同CTX组)、GnRH-ant+NS组[GnRH-ant 0.3 mg皮下注射,以后每隔2天注射1次,共4次(估计释放量为100μg/d,共12 d),于第1次GnRH-ant皮下注射后第2天开始注射NS,用药方法同对照组]及GnRH-ant+CTX组(同GnRH-ant+NS组注射GnRH-ant后,于第1次GnRH-ant皮下注射后第2天开始注射CTX,用药方法同CTX组];每组12只.用药前后采用酶联免疫吸附法动态检测各组大鼠卵泡刺激素(FSH)、黄体生成素(LH)及雌二醇水平的变化,并于结束用药后的第1周内和第4~5周内(动情间期),各组分别处死6只大鼠,观察卵泡数量、卵巢重量的变化.结果 (1)血清内分泌激素水平:用药前后,对照组的血清LH、FSH、雌二醇水平无明显变化,CTX组的血清内分泌激素水平呈上升趋势.用药中,血清LH、FSH水平GnRH-a+CTX组为(42±8)、(124±45)μg/L,GnRH-a+NS组为(47±7)、(136±32)μg/L;GnRH-ant+CTX组为(31±5)、(178±54)μg/L,GnRH-ant+NS组为(36±7)、(198±27)μg/L;对照组为(118±16)、(350±35)μg/L;CTX组为(113±15)、(289±42)μg/L;分别比较,差异均具有统计学意义(P<0.05).血清雌二醇水平GnRH-ant+CTX组为(3.98±0.74)ng/L,GnRH-ant+NS组为(3.58±0.43)ng/L,GnRH-a+CTX组为(1.46±0.22)ng/L,GnRH-a+NS组为(0.98±0.18)ng/L分别比较,差异均有统计学意义(P<0.01).停药后,GnRH-a+CTX组、GnRH-a+NS组及GnRH-ant+NS组的血清LH、FSH、雌二醇水平逐渐接近对照组水平.但停药第4~5周时,GnRH-ant+CTX组LH、FSH水平[(156±12)、(520±44)μg/L]与CTX组[(178±18)、(546±36)μg/L]比较,差异无统计学意义(P>0.05).(2)卵巢重量:停药第1周,GnRH-a+CTX组大鼠双侧卵巢重量为(18±8)mg/100 g,GnRH-a+NS组为(12±5)mg/100 g,均明显低于其他各组[(30±9)~(37±8)mg/100 g],差异均有统计学意义(P<0.05);停药第4~5周,GnRH-ant+CTX组大鼠双侧卵巢重量为(22±6)mg/100 g,CTX组为(20±4)mg/100 g,均明显低于其他各组,差异均有统计学意义(P<0.05).(3)卵泡数量:停药第1周,GnRH-a+CTX组大鼠卵巢原始卵泡数为(689±39)个,GnRH-a+NS组为(824±45)个,明显高于GnRH-ant+CTX组[(255±24)个]和CTX组[(343±29)个];生长卵泡数GnRH-a+CTX组为(21±3)个,GnRH-a+NS组为(15±1)个,明显低于GnRH-ant+CTX组[(110±21)个]和CTX组[(87±17)个];分别比较,差异均有统计学意义(P<0.05).停药第4~5周,GnRH-a+CTX组和GnRH-a+NS组的生长卵泡数[(56±16)、(58±11)个]接近对照组水平[(57±9)个];GnRH-ant+CTX组及CTX组的原始卵泡数和生长卵泡数均少于其他4组,差异均有统计学意义(P<0.05).结论 GnRH-a对CTX诱导的大鼠卵巢功能损害具有保护作用,GnRH-ant对CTX诱导的大鼠卵巢功能损害没有明显的保护作用.

  2. Clinical efficacy of gonadotropin releasing hormone agonist in treatment of severe endometriosis%促性腺激素释放激素激动剂治疗重度子宫内膜异位症的疗效分析

    杨茗钫; 何林生; 刘丝荪


    目的 观察并比较促性腺激素释放激素激动剂(GnRH-a)单用与反加疗法治疗重度子宫内膜异位症的临床疗效.方法 选取50例经保守手术证实为Ⅲ、Ⅳ期子宫内膜异位症的患者为研究对象,术后2个月内分别随机入选观察组诺雷德合用戊酸雌二醇及地屈孕酮治疗和对照组单用诺雷德治疗,比较两组患者治疗前、后生殖内分泌激素、血脂水平、凝血功能以及疼痛评分变化,观察治疗期间绝经相关症状,评价两种治疗方法的疗效及安全性.结果 (1)两组患者治疗结束时E2、FSH、LH均较治疗前显著降低,但观察组E2高于对照组,FSH低于对照组,差异具有统计学意义(P0.05).(3)观察组围绝经症状如潮热,情绪波动,骨、关节痛发生率显著低于对照组(P0.05).(3)The rate of menopausal symptoms in observation group were lower than control group (P<0.05). Conclusion Both two GnRH-a treatment had obvious clinical efficacy in the treatment for severe endometriosis,and the add-back therapy was more safety.

  3. Effect of short-term and prolonged stress on the biosynthesis of gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) in the hypothalamus and GnRHR in the pituitary of ewes during various physiological states.

    Ciechanowska, M; Łapot, M; Antkowiak, B; Mateusiak, K; Paruszewska, E; Malewski, T; Paluch, M; Przekop, F


    Using an ELISA assay, the levels of GnRH and GnRHR were analysed in the preoptic area (POA), anterior (AH) and ventromedial hypothalamus (VM), stalk/median eminence (SME); and GnRHR in the anterior pituitary gland (AP) of non-breeding and breeding sheep subjected to short-term or prolonged stress. The ELISA study was supplemented with an analysis of plasma LH concentration. Short-term footshock stimulation significantly increased GnRH levels in hypothalamus in both seasons. Prolonged stress elevated or decreased GnRH concentrations in the POA and the VM, respectively during anoestrus, and lowered GnRH amount in the POA-hypothalamus of follicular-phase sheep. An up-regulation of GnRHR levels was noted in both, anoestrous and follicular-phase animals. In the non-breeding period, a prolonged stress procedure increased GnRHR biosynthesis in the VM and decreased it in the SME and AP, while in the breeding time the quantities of GnRHR were significantly lower in the whole hypothalamus. In follicular-phase ewes the fluctuations of GnRH and GnRHR levels under short-term and prolonged stress were reflected in the changes of LH secretion, suggesting the existence of a direct relationship between GnRH and GnRH-R biosynthesis and GnRH/LH release in this period. The study showed that stress was capable of modulating the biosynthesis of GnRH and GnRHR; the pattern of changes was dependent upon the animal's physiological state and on the time course of stressor application. The obtained results indicate that the disturbances of gonadotropin secretion under stress conditions in sheep may be due to a dysfunction of GnRH and GnRHR biosynthetic pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Effect of Ubiquinol on Serum Reproductive Hormones of Amenorrhic Patients.

    Thakur, A S; Littaru, G P; Funahashi, I; Painkara, U S; Dange, N S; Chauhan, P


    In neuroendocrine system the increase in oxidative status is produced by a glucocorticoid-dependent and transcriptional increase in pro-oxidative drive, with concurrent inhibition of the antioxidant defense system, ultimately leading to increased neuronal cell death. Functional hypothalamic disturbances and neuroendocirne aberrations have both short and long term consequences for reproductive health. Understandably, an impaired or diminished hypothalamic-pituitary-ovarian axis leads to anovulation and hypoestrogenism. Anovulation is directly linked to the neurohormonal and hormonal background of Functional Hypothalamic Amenorrhea. Impairment of pulsatile Gonadotropin Releasing Hormone secretion causes the impairment of pulsatile Lutenizing Hormone (LH) and Follicle Stimulating Hormone (FSH) secretion. The importance of oxidative stress in various pituitary disorders suggesting a possible clinical usefulness of antioxidant molecules like the lipophilic antioxidant Ubiquinol. Coenzyme Q10 or Ubiquinol is an essential part of the cell energy-producing system of mitochondria. However, it is also a powerful lipophilic antioxidant, protecting lipoproteins and cell membranes from autooxidation. Due to these unique actions Ubiquinol is used in clinical practice as an antioxidants for neurodegenerative diseases. So to identify the role of Ubiquinol on reproductive hormones FSH and LH, we have included 50 infertile patients of age group of 20-40, which are mostly amenorrhic. Out of 50 only 30 patients were in continuous follow up after supplementing them with 150 mg of Ubiquinol every day for 4 months. The hormonal levels were estimated by Enzyme Linked Immuno Sorbent Assay technique at follicular phase. The result suggests that FSH concentration is increased up to three times (from 3.10 ± 2.70 to 10.09 ± 6.93) but remains within the normal limit (P  0.05). The supplementation of 150 mg of Ubiquinol may reduce the oxidative stress in neuroendocrine system which

  5. Treatment with thyroid hormone.

    Biondi, Bernadette; Wartofsky, Leonard


    Thyroid hormone deficiency can have important repercussions. Treatment with thyroid hormone in replacement doses is essential in patients with hypothyroidism. In this review, we critically discuss the thyroid hormone formulations that are available and approaches to correct replacement therapy with thyroid hormone in primary and central hypothyroidism in different periods of life such as pregnancy, birth, infancy, childhood, and adolescence as well as in adult patients, the elderly, and in patients with comorbidities. Despite the frequent and long term use of l-T4, several studies have documented frequent under- and overtreatment during replacement therapy in hypothyroid patients. We assess the factors determining l-T4 requirements (sex, age, gender, menstrual status, body weight, and lean body mass), the major causes of failure to achieve optimal serum TSH levels in undertreated patients (poor patient compliance, timing of l-T4 administration, interferences with absorption, gastrointestinal diseases, and drugs), and the adverse consequences of unintentional TSH suppression in overtreated patients. Opinions differ regarding the treatment of mild thyroid hormone deficiency, and we examine the recent evidence favoring treatment of this condition. New data suggesting that combined therapy with T3 and T4 could be indicated in some patients with hypothyroidism are assessed, and the indications for TSH suppression with l-T4 in patients with euthyroid multinodular goiter and in those with differentiated thyroid cancer are reviewed. Lastly, we address the potential use of thyroid hormones or their analogs in obese patients and in severe cardiac diseases, dyslipidemia, and nonthyroidal illnesses.




    The release of dopamine (DA) from tuberoinfundibular (TIDA) neurons during prolactin (PRL) surge and nonsurge periods and the effects of the thyrotropin-releasing hormone (TRH) analogue CG 3703 on DA and PRL secretion were studied in awake pseudopregnant (PSP) rats by simultaneous measurement of ext

  7. Analog and VLSI circuits

    Chen, Wai-Kai


    Featuring hundreds of illustrations and references, this book provides the information on analog and VLSI circuits. It focuses on analog integrated circuits, presenting the knowledge on monolithic device models, analog circuit cells, high performance analog circuits, RF communication circuits, and PLL circuits.

  8. Effect of cadmium on sexual hormone secretion from pituitary and ovary

    ZhanWC; WuZR


    The objective of this study is to provide the evidence of endocrine disruption induced by Cd.The changes of serum luteinizing hormone(LH),follicle stimulating hormone(FSH),progesterone(P) and estradiol(E2) levels were observed in female rats administrated ac with Cd.Serum FSH or LH was no significant difference between groups for 7-day and for 14-day exposure.But the serum E2 of the high dose group of 7-day exposure,the low dose and high dose group for 14d was significantly lower than that of the control group.Serum P of the low dose group of 7 day exposure was significantly lower than that of the control group.After injection of gonadotropin-release hormones (GnRH) the serum FSH and LH levels increased significantly in each group(Cd 0.5,1.0mg·kg-1,5days a week, for 6 weeks).However,the serum LH was lower significantly in the rats administrated Cd than in the control rats after the injection of GnRH.There was no difference of the number of ovum between groups(0,1.5,3.0mg·kg-1 for 5d) in the super-ovulation test(P>0.05).Cadmium has the distinct adverse effect on the ovary of female rats.But the response function of the ovary to excess gonadotropin was basically normal.Under this experimental conditions.the function of secual hormone secretion of pituitary has been damaged,but the normal level of both FSH and LH could be maintained because of the limited compensative function of pituitary.

  9. When Gesture Becomes Analogy.

    Cooperrider, Kensy; Goldin-Meadow, Susan


    Analogy researchers do not often examine gesture, and gesture researchers do not often borrow ideas from the study of analogy. One borrowable idea from the world of analogy is the importance of distinguishing between attributes and relations. Gentner (, ) observed that some metaphors highlight attributes and others highlight relations, and called the latter analogies. Mirroring this logic, we observe that some metaphoric gestures represent attributes and others represent relations, and propose to call the latter analogical gestures. We provide examples of such analogical gestures and show how they relate to the categories of iconic and metaphoric gestures described previously. Analogical gestures represent different types of relations and different degrees of relational complexity, and sometimes cohere into larger analogical models. Treating analogical gestures as a distinct phenomenon prompts new questions and predictions, and illustrates one way that the study of gesture and the study of analogy can be mutually informative. Copyright © 2017 Cognitive Science Society, Inc.

  10. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation.

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L; Deviche, Pierre


    Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary-gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity.

  11. Hormonal Regulation of Expression of Tissue Type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 in Cultured Rat Granulosa Cells

    刘以训; 彭晓蓉; 刘奎


    In the present study, gonadotropin and gonadotropin-releasing hormone (GnRH) regulation of tPA and PAI-1 expression in PMSG-primed granulosa cells has been investigated, (i) Addition of go-nadotropins (FSH and LH) and GnRH agonist (GnRHa) or PMA to the culture increases tPA activity) FSH (or LH) plus GnRHa (or PMA) in the culture further enhances the enzyme production to such an extent that a more obvious effect than the additive effect caused by these hormones used alone has been observed; (ii) in contrast, FSH and LH decrease PAI-1 activity, whereas GnRHa and PMA alone markedly increase PAI-1 mRNA level and PAI-1 activity. Because FSH and LH stimulate tPA production and have no significant effect on PAI-1 mRNA induction, the observed inhibition of PAI-1 activity by gonadotropins may be due to the occurrence of neutralization of PA and PAI-1 proteins in the conditioned media by the formation of complexes between PA and PAI-1 ; (iii) increases in PAI-1 mRNA level and activity by GnRH and PMA are complet

  12. Functional and neurophysiological evidence of the efficacy of trophic repair pharmacotherapy using an adrenocorticotrophic hormone4-9 analog in experimental allergic encephalomyelitis, an animal model of multiple sclerosis

    Gispen, W. H.; Duckers, H.J.; van Dokkum, R.P.; Verhaagen, J; Lopes da Silva, F.H.


    Chronic experimental allergic encephalomyelitis (CEAE) is a well-established animal model for the human syndrome, multiple sclerosis. CEAE has striking histological, electrophysiological and clinical analogies with multiple sclerosis and is a valuable animal model for the preclinical pharmacotherapeutical development of new putative therapeutic agents. In this paper, we describe a neurotrophic repair approach in Lewis rats suffering from CEAE. The neurotrophic peptide used is a degradation re...

  13. Differential regulation of gonadotropins (FSH and LH) and growth hormone (GH) by neuroendocrine, endocrine, and paracrine factors in the zebrafish--an in vitro approach.

    Lin, Sze-Wah; Ge, Wei


    Recently, zebrafish has quickly risen as a model species for functional analysis of the brain-pituitary-gonad axis. However, one of the hurdles for such work in this popular model organism is the small size of its pituitary gland, which makes it difficult to investigate the regulation of pituitary hormone expression and secretion in vitro. To provide a solution to this problem and demonstrate the value of zebrafish in reproductive endocrinology, the present study was undertaken to establish a primary pituitary cell culture followed by investigating the regulation of FSHbeta (fshb), LHbeta (lhb), and GH (gh) expression by a variety of neuroendocrine, endocrine, and paracrine factors. All the factors examined influenced the expression of fshb, lhb, and ghin vitro except epidermal growth factor (EGF) despite the expression of its receptor egfr in the pituitary. Acting in a similar manner, gonadal steroids (estradiol and testosterone) stimulated both fshb and lhb, but had no effect on gh. In contrast, all other factors tested (gonadotropin-releasing hormone, GnRH; pituitary adenylate cyclase-activating polypeptide, PACAP; activin/follistatin, and insulin-like growth factor I, IGF-I) exhibited distinct effects on the expression of the three target genes studied, suggesting roles for these factors in the differential regulation of two gonadotropins and growth hormone and therefore the gonadotrophic and somatotrophic axes.

  14. Learning by Analogy: Discriminating between Potential Analogs

    Richland, Lindsey E.; McDonough, Ian M.


    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  15. Intuitive analog circuit design

    Thompson, Marc


    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  16. NCBI nr-aa BLAST: CBRC-TNIG-22-0119 [SEVENS

    Full Text Available CBRC-TNIG-22-0119 ref|NP_001098392.1| gonadotropin-releasing hormone receptor 2 [Oryzias latipes...] dbj|BAB70503.1| gonadotropin-releasing hormone receptor 2 [Oryzias latipes] dbj|BAB70505.1| g...onadotropin-releasing hormone receptor 2 [Oryzias latipes] NP_001098392.1 1e-158 79% ...

  17. NCBI nr-aa BLAST: CBRC-DRER-26-0232 [SEVENS

    Full Text Available CBRC-DRER-26-0232 ref|NP_001098392.1| gonadotropin-releasing hormone receptor 2 [Oryzias latipes...] dbj|BAB70503.1| gonadotropin-releasing hormone receptor 2 [Oryzias latipes] dbj|BAB70505.1| g...onadotropin-releasing hormone receptor 2 [Oryzias latipes] NP_001098392.1 2e-80 49% ...

  18. NCBI nr-aa BLAST: CBRC-TNIG-22-0303 [SEVENS

    Full Text Available CBRC-TNIG-22-0303 ref|NP_001098352.1| gonadotropin-releasing hormone receptor 1 [Oryzias latipes...] dbj|BAB70504.1| gonadotropin-releasing hormone receptor 1 [Oryzias latipes] dbj|BAB70506.1| g...onadotropin-releasing hormone receptor 1 [Oryzias latipes] NP_001098352.1 1e-130 70% ...

  19. NCBI nr-aa BLAST: CBRC-OLAT-26-0130 [SEVENS

    Full Text Available CBRC-OLAT-26-0130 ref|NP_001098352.1| gonadotropin-releasing hormone receptor 1 [Oryzias latipes...] dbj|BAB70504.1| gonadotropin-releasing hormone receptor 1 [Oryzias latipes] dbj|BAB70506.1| g...onadotropin-releasing hormone receptor 1 [Oryzias latipes] NP_001098352.1 0.0 99% ...

  20. Localization and functional characterization of a novel adipokinetic hormone in the mollusk, Aplysia californica.

    Joshua I Johnson

    Full Text Available Increasing evidence suggests that gonadotropin-releasing hormone (GnRH, corazonin, adipokinetic hormone (AKH, and red pigment-concentrating hormone all share common ancestry to form a GnRH superfamily. Despite the wide presence of these peptides in protostomes, their biological effects remain poorly characterized in many taxa. This study had three goals. First, we cloned the full-length sequence of a novel AKH, termed Aplysia-AKH, and examined its distribution in an opisthobranch mollusk, Aplysia californica. Second, we investigated in vivo biological effects of Aplysia-AKH. Lastly, we compared the effects of Aplysia-AKH to a related A. californica peptide, Aplysia-GnRH. Results suggest that Aplysia-AKH mRNA and peptide are localized exclusively in central tissues, with abdominal, cerebral, and pleural ganglia being the primary sites of Aplysia-AKH production. However, Aplysia-AKH-positive fibers were found in all central ganglia, suggesting diverse neuromodulatory roles. Injections of A. californica with Aplysia-AKH significantly inhibited feeding, reduced body mass, increased excretion of feces, and reduced gonadal mass and oocyte diameter. The in vivo effects of Aplysia-AKH differed substantially from Aplysia-GnRH. Overall, the distribution and biological effects of Aplysia-AKH suggest it has diverged functionally from Aplysia-GnRH over the course of evolution. Further, that both Aplysia-AKH and Aplysia-GnRH failed to activate reproduction suggest the critical role of GnRH as a reproductive activator may be a phenomenon unique to vertebrates.

  1. Localization and Functional Characterization of a Novel Adipokinetic Hormone in the Mollusk, Aplysia californica

    Johnson, Joshua I.; Kavanaugh, Scott I.; Nguyen, Cindy; Tsai, Pei-San


    Increasing evidence suggests that gonadotropin-releasing hormone (GnRH), corazonin, adipokinetic hormone (AKH), and red pigment-concentrating hormone all share common ancestry to form a GnRH superfamily. Despite the wide presence of these peptides in protostomes, their biological effects remain poorly characterized in many taxa. This study had three goals. First, we cloned the full-length sequence of a novel AKH, termed Aplysia-AKH, and examined its distribution in an opisthobranch mollusk, Aplysia californica. Second, we investigated in vivo biological effects of Aplysia-AKH. Lastly, we compared the effects of Aplysia-AKH to a related A. californica peptide, Aplysia-GnRH. Results suggest that Aplysia-AKH mRNA and peptide are localized exclusively in central tissues, with abdominal, cerebral, and pleural ganglia being the primary sites of Aplysia-AKH production. However, Aplysia-AKH-positive fibers were found in all central ganglia, suggesting diverse neuromodulatory roles. Injections of A. californica with Aplysia-AKH significantly inhibited feeding, reduced body mass, increased excretion of feces, and reduced gonadal mass and oocyte diameter. The in vivo effects of Aplysia-AKH differed substantially from Aplysia-GnRH. Overall, the distribution and biological effects of Aplysia-AKH suggest it has diverged functionally from Aplysia-GnRH over the course of evolution. Further, that both Aplysia-AKH and Aplysia-GnRH failed to activate reproduction suggest the critical role of GnRH as a reproductive activator may be a phenomenon unique to vertebrates. PMID:25162698

  2. Survival improvement in hormone-responsive young breast cancer patients with endocrine therapy.

    Yoon, Tae In; Hwang, Ui-Kang; Kim, Eui Tae; Lee, SaeByul; Sohn, Guiyun; Ko, Beom Seok; Lee, Jong Won; Son, Byung Ho; Kim, Seonok; Ahn, Sei Hyun; Kim, Hee Jeong


    We investigated the oncologic outcomes by intrinsic subtype and age in young breast cancer patients and whether survival differences were related to treatment changes over time. A retrospective analysis was performed on 9633 invasive breast cancer patients treated at Asan Medical Center from January 1989 to December 2008. We also enrolled a matched cohort adjusting for tumor size, lymph node metastasis, subtypes, and tumor grade. Patients aged <35 years were included in the younger group (n = 602) and those aged ≥35 years were included in the older group (n = 3009). The younger patients showed a significantly higher T stage, a more frequent axillary node presentation, higher histologic grade, and higher incidence of triple-negative subtype tumors than older patients and also received more chemotherapy and were less likely to undergo hormone therapy. The younger patients with hormone receptor (HR)-positive tumors showed significantly poorer disease-free survival (DFS), loco-regional recurrence-free survival, distant metastasis-free survival, and breast cancer-specific survival outcomes than older patients. Younger patients with HR-positive and human epidermal growth factor receptor 2 (HER2)-negative tumor subtypes had a significantly improved DFS over time (p = 0.032). Within the HR-positive/Her2-negative subtype, more women received gonadotropin-releasing hormone agonist and tamoxifen treatment from 2003 to 2008 compared with 1989 to 2002 (p = 0.001 and p = 0.075, respectively). HR-positive young breast cancer patients have a poorer survival compared with older patients, even with more frequent chemotherapy, but more recent use of tamoxifen and ovarian suppression might improve this outcome in these patients.

  3. Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women.

    Rao, C V


    Alzheimer disease (AD) is a slow progressive neurodegenerative disease that affects more elderly women than elderly men. It impairs memory, typically progresses into multidomain cognitive decline that destroys the quality of life, and ultimately leads to death. About 5.3 million older Americans are now living with this disease, and this number is projected to rise to 14 million by 2050. Annual health-care costs in the United States alone are projected to increase to about US$1.1 trillion by 2050. The initial theory that decreasing estrogen levels leads to AD development in postmenopausal women has been proven inconclusive. For example, Women's Health Research Initiative Memory Study and the population-based nested case-control study have failed to demonstrate that estrogen/progesterone (hormone replacement therapy [HRT]) or estrogen replacement therapy could prevent the cognitive decline or reduce the risk of AD. This led to the realization that AD development could be due to a progressive increase in luteinizing hormone (LH) levels in postmenopausal women. Accordingly, a large number of studies have demonstrated that an increase in LH levels is positively correlated with neuropathological, behavioral, and cognitive changes in AD. In addition, LH has been shown to promote amyloidogenic pathway of precursor protein metabolism and deposition of amyloid β plaques in the hippocampus, a region involved in AD. Cognate receptors that mediate LH effects are abundantly expressed in the hippocampus. Reducing the LH levels by treatment with gonadotropin-releasing hormone agonists could provide therapeutic benefits. Despite these advances, many questions remain and require further research.

  4. Analog and hybrid computing

    Hyndman, D E


    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  5. Structured Analog CMOS Design

    Stefanovic, Danica


    Structured Analog CMOS Design describes a structured analog design approach that makes it possible to simplify complex analog design problems and develop a design strategy that can be used for the design of large number of analog cells. It intentionally avoids treating the analog design as a mathematical problem, developing a design procedure based on the understanding of device physics and approximations that give insight into parameter interdependences. The proposed transistor-level design procedure is based on the EKV modeling approach and relies on the device inversion level as a fundament

  6. Molecular cloning of the cDNA encoding follicle-stimulating hormone beta subunit of the Chinese soft-shell turtle Pelodiscus sinensis, and its gene expression.

    Chien, Jung-Tsun; Shen, San-Tai; Lin, Yao-Sung; Yu, John Yuh-Lin


    Follicle-stimulating hormone (FSH) is a member of the pituitary glycoprotein hormone family. These hormones are composed of two dissimilar subunits, alpha and beta. Very little information is available regarding the nucleotide and amino acid sequence of FSHbeta in reptilian species. For better understanding of the phylogenetic diversity and evolution of FSH molecule, we have isolated and sequenced the complementary DNA (cDNA) encoding the Chinese soft-shell turtle (Pelodiscus sinensis, Family of Trionychidae) FSHbeta precursor molecule by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) methods. The cloned Chinese soft-shell turtle FSHbeta cDNA consists of 602-bp nucleotides, including 34-bp nucleotides of the 5'-untranslated region (UTR), 396-bp of the open reading frame, and 3'-UTR of 206-bp nucleotides. It encodes a 131-amino acid precursor molecule of FSHbeta subunit with a signal peptide of 20 amino acids followed by a mature protein of 111 amino acids. Twelve cysteine residues, forming six disulfide bonds within beta-subunit and two putative asparagine-linked glycosylation sites, are also conserved in the Chinese soft-shell turtle FSHbeta subunit. The deduced amino acid sequence of the Chinese soft-shell turtle FSHbeta shares identities of 97% with Reeves's turtle (Family of Bataguridae), 83-89% with birds, 61-70% with mammals, 63-66% with amphibians and 40-58% with fish. By contrast, when comparing the FSHbeta with the beta-subunits of the Chinese soft-shell turtle luteinizing hormone and thyroid stimulating hormone, the homologies are as low as 38 and 39%, respectively. A phylogenetic tree including reptilian species of FSHbeta subunits, is presented for the first time. Out of various tissues examined, FSHbeta mRNA was only expressed in the pituitary gland and can be up-regulated by gonadotropin-releasing hormone in pituitary tissue culture as estimated by fluorescence real-time PCR analysis.

  7. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G


    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.

  8. Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study

    Henningsson, S; Madsen, K H; Pinborg, A; Heede, M; Knudsen, G M; Siebner, H R; Frokjaer, V G


    Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood−oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16±3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum. PMID:26624927

  9. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    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)


    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.)

  10. Analogies of Information Security

    Sole, Amund Bauck


    In this thesis it will be tested wither analogies and metaphors would make it easier to teach the fundamental subjects of information security and hacking to people with no previous background in computer science and only basic computer skills. This will be done by conducting interview on people with no background in computer science to see what analogies work the best for different topics in information security. From the analogy getting the best response, a small game will be designed with ...

  11. Analog circuit design

    Dobkin, Bob


    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply i